SemOpenAlex |

SemOpenAlex

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2096567265> ?p ?o ?g. }

Showing items 1 to 100 of ±115 with 100 items per page.

W2096567265 endingPage "153" @default.
W2096567265 startingPage "144" @default.
W2096567265 abstract "The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in ∼3,000 subjects. The rare alleles of the −1464T>C, −1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19–86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the −1464T>C polymorphism had no effect by itself but was a marker for the −1131T>C, S19W, and 1259T>C polymorphisms. The −1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 −1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in ∼40% of the Turks. Similar associations were observed for −1131T>C and S19W in white Americans living in San Francisco, California. The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in ∼3,000 subjects. The rare alleles of the −1464T>C, −1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19–86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the −1464T>C polymorphism had no effect by itself but was a marker for the −1131T>C, S19W, and 1259T>C polymorphisms. The −1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 −1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in ∼40% of the Turks. Similar associations were observed for −1131T>C and S19W in white Americans living in San Francisco, California. Atherogenic dyslipidemia, including hypertriglyceridemia, is a risk factor for coronary artery disease (CAD) (1Murray C.J.L. Lopez A.D. Mortality by cause for eight regions of the world. Global Burden of Disease Study.Lancet. 1997; 349: 1269-1276Google Scholar, 2Peto R. Lopez A.D. Boreham J. Thun M. Heath Jr., C. Doll R. Mortality from smoking worldwide.Br. Med. Bull. 1996; 52: 12-21Google Scholar). Family and twin studies have shown that triglyceride levels are controlled by genetic factors, although heritability estimates vary widely (3Brenn T. Genetic and environmental effects on coronary heart disease risk factors in Northern Norway. The cardiovascular disease study in Finnmark.Ann. Hum. Genet. 1994; 58: 369-379Google Scholar, 4Heller D.A. de Faire U. Pedersen N.L. Dahlén G. McClearn G.E. Genetic and environmental influences on serum lipid levels in twins.N. Engl. J. Med. 1993; 328: 1150-1156Google Scholar, 5Pérusse L. Rice T. Després J.P. Bergeron J. Province M.A. Gagnon J. Leon A.S. Rao D.C. Skinner J.S. Wilmore J.H. et al.Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE family study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 3263-3269Google Scholar). Recently, the multinational Genetic Epidemiology of Metabolic Syndrome project (6Wyszynski D.F. Waterworth D.M. Barter P.J. Cohen J. Kesäniemi Y.A. Mahley R.W. McPherson R. Waeber G. Bersot T.P. Sharma S.S. et al.Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project).Am. J. Cardiol. 2005; 95: 194-198Google Scholar) conducted a genome scan for atherogenic dyslipidemia and found significant evidence for linkage to triglyceride levels near the apolipoprotein A-V gene (APOA5), on chromosome 11q22, only in Turkish families (7Yu Y. Wyszynski D.F. Waterworth D.M. Wilton S.D. Barter P.J. Kesäniemi Y.A. Mahley R.W. McPherson R. Waeber G. Bersot T.P. et al.Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.J. Lipid Res. 2005; 46: 2202-2213Google Scholar). ApoA-V is an important regulator of plasma triglyceride levels (8Pennacchio L.A. Olivier M. Hubacek J.A. Cohen J.C. Cox D.R. Fruchart J-C. Krauss R.M. Rubin E.M. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.Science. 2001; 294: 169-173Google Scholar, 9van der Vliet H.N. Sehaap F.G. Levels J.H.M. Ottenhoff R. Looije N. Wesseling J.G. Groen A.K. Chamuleau R.A.F.M. Adenoviral overexpression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice.Biochem. Biophys. Res. Commun. 2002; 295: 1156-1159Google Scholar). Triglyceride levels are 4-fold higher in Apoa5 knockout mice and significantly lower in transgenic mice (8Pennacchio L.A. Olivier M. Hubacek J.A. Cohen J.C. Cox D.R. Fruchart J-C. Krauss R.M. Rubin E.M. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.Science. 2001; 294: 169-173Google Scholar) or in adenovirus-treated mice expressing human APOA5 (9van der Vliet H.N. Sehaap F.G. Levels J.H.M. Ottenhoff R. Looije N. Wesseling J.G. Groen A.K. Chamuleau R.A.F.M. Adenoviral overexpression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice.Biochem. Biophys. Res. Commun. 2002; 295: 1156-1159Google Scholar) than in wild-type mice. ApoA5 may decrease plasma triglyceride levels by increasing lipoprotein lipase activity (10Fruchart-Najib J. Baugé E. Niculescu L-S. Pham T. Thomas B. Rommens C. Majd Z. Brewer B. Pennacchio L.A. Fruchart J-C. Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5.Biochem. Biophys. Res. Commun. 2004; 319: 397-404Google Scholar, 11Schaap F.G. Rensen P.C.N. Voshol P.J. Vrins C. van der Vliet H.N. Chamuleau R.A.F.M. Havekes L.M. Groen A.K. van Dijk K.W. ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.J. Biol. Chem. 2004; 279: 27941-27947Google Scholar) and reducing hepatic levels of very low density lipoprotein triglyceride (11Schaap F.G. Rensen P.C.N. Voshol P.J. Vrins C. van der Vliet H.N. Chamuleau R.A.F.M. Havekes L.M. Groen A.K. van Dijk K.W. ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.J. Biol. Chem. 2004; 279: 27941-27947Google Scholar). Several single nucleotide polymorphisms (SNPs) within the APOA5 locus (−1131T>C, −3A>G, S19W, IVS3+476G>A, 1259T>C, and G185C) have been identified, and their rare alleles are associated with increased plasma triglyceride levels in different populations (8Pennacchio L.A. Olivier M. Hubacek J.A. Cohen J.C. Cox D.R. Fruchart J-C. Krauss R.M. Rubin E.M. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.Science. 2001; 294: 169-173Google Scholar, 12Aouizerat B.E. Kulkarni M. Heilbron D. Drown D. Raskin S. Pullinger C.R. Malloy M.J. Kane J.P. Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids.J. Lipid Res. 2003; 44: 1167-1173Google Scholar, 13Austin M.A. Talmud P.J. Farin F.M. Nickerson D.A. Edwards K.L. Leonetti D. McNeely M.J. Viernes H-M. Humphries S.E. Fujimoto W.Y. Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans.Biochim. Biophys. Acta. 2004; 1688: 1-9Google Scholar, 14Baum L. Tomlinson B. Thomas G.N. APOA5-1131T>C polymorphism is associated with triglyceride levels in Chinese men.Clin. Genet. 2003; 63: 377-379Google Scholar, 15Kao J-T. Wen H-C. Chien K-L. Hsu H-C. Lin S-W. A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.Hum. Mol. Genet. 2003; 12: 2533-2539Google Scholar, 16Lai C-Q. Tai E-S. Tan C.E. Cutter J. Chew S.K. Zhu Y-P. Adiconis X. Ordovas J.M. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.J. Lipid Res. 2003; 44: 2365-2373Google Scholar, 17Lai C-Q. Demissie S. Cupples L.A. Zhu Y. Adiconis X. Parnell L.D. Corella D. Ordovas J.M. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.J. Lipid Res. 2004; 45: 2096-2105Google Scholar, 18Martin S. Nicaud V. Humphries S.E. Talmud P.J. Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges.Biochim. Biophys. Acta. 2003; 1637: 217-225Google Scholar, 19Nabika T. Nasreen S. Kobayashi S. Masuda J. The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese.Atherosclerosis. 2002; 165: 201-204Google Scholar, 20Pennacchio L.A. Olivier M. Hubacek J.A. Krauss R.M. Rubin E.M. Cohen J.C. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Hum. Mol. Genet. 2002; 11: 3031-3038Google Scholar, 21Talmud P.J. Hawe E. Martin S. Olivier M. Miller G.J. Rubin E.M. Pennacchio L.A. Humphries S.E. Relative contribution of variation within theAPOC3/A4/A5 gene cluster in determining plasma triglycerides.Hum. Mol. Genet. 2002; 11: 3039-3046Google Scholar, 22Klos K.L.E. Hamon S. Clark A.G. Boerwinkle E. Liu K. Sing C.F. APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study.J. Lipid Res. 2005; 46: 564-570Google Scholar). The −1131T>C, −3A>G, IVS3+476G>A, and 1259T>C SNPs (haplotype APOA5*2) were in almost complete linkage disequilibrium (LD) in European populations (17Lai C-Q. Demissie S. Cupples L.A. Zhu Y. Adiconis X. Parnell L.D. Corella D. Ordovas J.M. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.J. Lipid Res. 2004; 45: 2096-2105Google Scholar, 20Pennacchio L.A. Olivier M. Hubacek J.A. Krauss R.M. Rubin E.M. Cohen J.C. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Hum. Mol. Genet. 2002; 11: 3031-3038Google Scholar). Therefore, any one of these polymorphisms might serve as a marker for the others in these populations. The frequencies of the rare alleles of −1131T>C and S19W vary greatly among populations (8Pennacchio L.A. Olivier M. Hubacek J.A. Cohen J.C. Cox D.R. Fruchart J-C. Krauss R.M. Rubin E.M. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.Science. 2001; 294: 169-173Google Scholar, 12Aouizerat B.E. Kulkarni M. Heilbron D. Drown D. Raskin S. Pullinger C.R. Malloy M.J. Kane J.P. Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids.J. Lipid Res. 2003; 44: 1167-1173Google Scholar, 13Austin M.A. Talmud P.J. Farin F.M. Nickerson D.A. Edwards K.L. Leonetti D. McNeely M.J. Viernes H-M. Humphries S.E. Fujimoto W.Y. Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans.Biochim. Biophys. Acta. 2004; 1688: 1-9Google Scholar, 14Baum L. Tomlinson B. Thomas G.N. APOA5-1131T>C polymorphism is associated with triglyceride levels in Chinese men.Clin. Genet. 2003; 63: 377-379Google Scholar, 15Kao J-T. Wen H-C. Chien K-L. Hsu H-C. Lin S-W. A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.Hum. Mol. Genet. 2003; 12: 2533-2539Google Scholar, 16Lai C-Q. Tai E-S. Tan C.E. Cutter J. Chew S.K. Zhu Y-P. Adiconis X. Ordovas J.M. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.J. Lipid Res. 2003; 44: 2365-2373Google Scholar, 17Lai C-Q. Demissie S. Cupples L.A. Zhu Y. Adiconis X. Parnell L.D. Corella D. Ordovas J.M. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.J. Lipid Res. 2004; 45: 2096-2105Google Scholar, 18Martin S. Nicaud V. Humphries S.E. Talmud P.J. Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges.Biochim. Biophys. Acta. 2003; 1637: 217-225Google Scholar, 19Nabika T. Nasreen S. Kobayashi S. Masuda J. The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese.Atherosclerosis. 2002; 165: 201-204Google Scholar, 20Pennacchio L.A. Olivier M. Hubacek J.A. Krauss R.M. Rubin E.M. Cohen J.C. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Hum. Mol. Genet. 2002; 11: 3031-3038Google Scholar, 21Talmud P.J. Hawe E. Martin S. Olivier M. Miller G.J. Rubin E.M. Pennacchio L.A. Humphries S.E. Relative contribution of variation within theAPOC3/A4/A5 gene cluster in determining plasma triglycerides.Hum. Mol. Genet. 2002; 11: 3039-3046Google Scholar, 22Klos K.L.E. Hamon S. Clark A.G. Boerwinkle E. Liu K. Sing C.F. APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study.J. Lipid Res. 2005; 46: 564-570Google Scholar). The plasma triglyceride increase associated with these rare alleles also varies, ranging from no association (20Pennacchio L.A. Olivier M. Hubacek J.A. Krauss R.M. Rubin E.M. Cohen J.C. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Hum. Mol. Genet. 2002; 11: 3031-3038Google Scholar, 22Klos K.L.E. Hamon S. Clark A.G. Boerwinkle E. Liu K. Sing C.F. APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study.J. Lipid Res. 2005; 46: 564-570Google Scholar) to 69% higher triglyceride levels in CC than in TT subjects with the −1131T>C polymorphism (16Lai C-Q. Tai E-S. Tan C.E. Cutter J. Chew S.K. Zhu Y-P. Adiconis X. Ordovas J.M. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.J. Lipid Res. 2003; 44: 2365-2373Google Scholar) and from no association (23Lee K.W.J. Ayyobi A.F. Frohlich J.J. Hill J.S. APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease.Atherosclerosis. 2004; 176: 165-172Google Scholar, 24Talmud P.J. Martin S. Taskinen M-R. Frick M.H. Nieminen M.S. Kesäniemi Y.A. Pasternack A. Humphries S.E. Syvänne M. APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study.J. Lipid Res. 2004; 45: 750-756Google Scholar) to 20–30% higher triglyceride levels in SW than in SS subjects with the S19W polymorphism (20Pennacchio L.A. Olivier M. Hubacek J.A. Krauss R.M. Rubin E.M. Cohen J.C. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Hum. Mol. Genet. 2002; 11: 3031-3038Google Scholar). Haplotype analysis in European populations identified three common haplotypes, two of which, uniquely described by the rare alleles −1131T>C and S19W, are associated with higher triglyceride levels than the most common haplotype (18Martin S. Nicaud V. Humphries S.E. Talmud P.J. Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges.Biochim. Biophys. Acta. 2003; 1637: 217-225Google Scholar, 20Pennacchio L.A. Olivier M. Hubacek J.A. Krauss R.M. Rubin E.M. Cohen J.C. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.Hum. Mol. Genet. 2002; 11: 3031-3038Google Scholar, 21Talmud P.J. Hawe E. Martin S. Olivier M. Miller G.J. Rubin E.M. Pennacchio L.A. Humphries S.E. Relative contribution of variation within theAPOC3/A4/A5 gene cluster in determining plasma triglycerides.Hum. Mol. Genet. 2002; 11: 3039-3046Google Scholar). Although haplotype structure and distributions were different in Chinese (15Kao J-T. Wen H-C. Chien K-L. Hsu H-C. Lin S-W. A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.Hum. Mol. Genet. 2003; 12: 2533-2539Google Scholar), African-Americans (22Klos K.L.E. Hamon S. Clark A.G. Boerwinkle E. Liu K. Sing C.F. APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study.J. Lipid Res. 2005; 46: 564-570Google Scholar), and three different Singaporean populations (16Lai C-Q. Tai E-S. Tan C.E. Cutter J. Chew S.K. Zhu Y-P. Adiconis X. Ordovas J.M. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.J. Lipid Res. 2003; 44: 2365-2373Google Scholar), significant haplotype-triglyceride associations were identified. APOA5 SNPs have also been associated with reduced high density lipoprotein cholesterol (HDL-C; −1131T>C, −3A>G, and IVS3+476A>G) (16Lai C-Q. Tai E-S. Tan C.E. Cutter J. Chew S.K. Zhu Y-P. Adiconis X. Ordovas J.M. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.J. Lipid Res. 2003; 44: 2365-2373Google Scholar), decreased LDL cholesterol size (1259T>C and −3A>G) (13Austin M.A. Talmud P.J. Farin F.M. Nickerson D.A. Edwards K.L. Leonetti D. McNeely M.J. Viernes H-M. Humphries S.E. Fujimoto W.Y. Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans.Biochim. Biophys. Acta. 2004; 1688: 1-9Google Scholar), and increased numbers of remnant-like particles (−1131T>C and S19W) (17Lai C-Q. Demissie S. Cupples L.A. Zhu Y. Adiconis X. Parnell L.D. Corella D. Ordovas J.M. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.J. Lipid Res. 2004; 45: 2096-2105Google Scholar). The −1131T>C SNP was more frequent in CAD patients (25Szalai C. Keszei M. Duba J. Prohászka Z. Kozma G.T. Császár A. Balogh S. Almássy Z. Fust G. Czinner A. Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease.Atherosclerosis. 2004; 173: 109-114Google Scholar). Both the −1131T>C and S19W SNPs were associated with cardiovascular events (17Lai C-Q. Demissie S. Cupples L.A. Zhu Y. Adiconis X. Parnell L.D. Corella D. Ordovas J.M. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.J. Lipid Res. 2004; 45: 2096-2105Google Scholar) but not with coronary artery diameter (23Lee K.W.J. Ayyobi A.F. Frohlich J.J. Hill J.S. APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease.Atherosclerosis. 2004; 176: 165-172Google Scholar). In this study, we explored the association between APOA5 sequence variations and plasma triglyceride levels in >3,000 participants in the Turkish Heart Study (THS), a large, cross-sectional epidemiological survey of the Turkish population (26Mahley R.W. Palaoğlu K.E. Atak Z. Dawson-Pepin J. Langlois A.-M. Cheung V. Onat H. Fulks P. Mahley L.L. Vakar F. et al.Turkish Heart Study. Lipids, lipoproteins, and apolipoproteins.J. Lipid Res. 1995; 36: 839-859Google Scholar). The APOA5 gene was sequenced to detect polymorphisms, haplotype-tagging single nucleotide polymorphisms (htSNPs) were genotyped, and these SNPs and haplotypes were associated with significantly increased levels of triglycerides. The primary study population consisted of 3,020 subjects randomly selected from the THS (26Mahley R.W. Palaoğlu K.E. Atak Z. Dawson-Pepin J. Langlois A.-M. Cheung V. Onat H. Fulks P. Mahley L.L. Vakar F. et al.Turkish Heart Study. Lipids, lipoproteins, and apolipoproteins.J. Lipid Res. 1995; 36: 839-859Google Scholar). A second cohort of 802 self-reported white American bank employees from a broad range of socioeconomic levels was used for some assays (27Bersot T.P. Russell S.J. Thatcher S.R. Pomernacki N.K. Mahley R.W. Weisgraber K.H. Innerarity T.L. Fox C.S. A unique haplotype of the apolipoprotein B-100 allele associated with familial defective apolipoprotein B-100 in a Chinese man discovered during a study of the prevalence of this disorder.J. Lipid Res. 1993; 34: 1149-1154Google Scholar). Detailed biodata and blood samples obtained after an overnight fast were collected for each subject. Plasma lipids were measured as described (26Mahley R.W. Palaoğlu K.E. Atak Z. Dawson-Pepin J. Langlois A.-M. Cheung V. Onat H. Fulks P. Mahley L.L. Vakar F. et al.Turkish Heart Study. Lipids, lipoproteins, and apolipoproteins.J. Lipid Res. 1995; 36: 839-859Google Scholar). The protocols were approved by the Committee on Human Research of the University of California, San Francisco, and were in accordance with the Helsinki Declaration. Subjects who were taking lipid-lowering medication, had a history of diabetes mellitus, or had a plasma triglyceride level > 800 mg/dl were excluded. Primers were designed to amplify across the APOA5 promoter, the 5′ untranslated region (UTR), and all exons, including intron/exon splicing boundaries when possible. DNA from 23 subjects (13 THS participants and 10 white Americans) was sequenced to identify polymorphisms in APOA5. DNA sequences were aligned and analyzed with Sequencher DNA analysis software (Gene Codes, Ann Arbor, MI). After amplification by polymerase chain reaction, each polymorphism was genotyped by restriction fragment length polymorphism, digesting the primary amplification with restriction endonucleases and separating the resulting fragments with 1–3% agarose gels. The conditions of all assays are described in supplementary Table 1.TABLE 1.Demographic and biochemical characteristics of Turkish Heart Study participants (n = 3,020)VariableMales (n = 1,661)Females (n = 1,359)PAge (years)42 ± 1342 ± 15NSBody mass index (kg/m2)26.1 ± 3.926.6 ± 5.4<0.05HDL cholesterol (mg/dl)35.8 ± 7.541.2 ± 9<0.001Total cholesterol (mg/dl)184 ± 45183 ± 42NSLDL cholesterol (mg/dl)126 ± 41116 ± 39<0.05Triglycerides (mg/dl)153 ± 107110 ± 70<0.001Total cholesterol/HDL cholesterol ratio5.8 ± 2.94.5 ± 1.4<0.01Systolic blood pressure (mm Hg)125 ± 23122 ± 21NSDiastolic blood pressure (mm Hg)82 ± 1481 ± 13NSConsumption of alcohol (%)aOne or more drinks per week.29.95.5<0.001Cigarette smoking (%)bOne or more cigarettes per day.56.724.1<0.001Values are means ± SD or percentages. Means were compared by t-test, and percentages were analyzed by chi-square test.a One or more drinks per week.b One or more cigarettes per day. Open table in a new tab Values are means ± SD or percentages. Means were compared by t-test, and percentages were analyzed by chi-square test. Data were analyzed with SPSS 10.0, Microsoft Access, and Excel. Associations between genotypes, lipids, and other parameters were analyzed separately for males and females. Lipid levels are expressed in mg/dl, and all values are reported as means ± SD. Mean values were compared with the t-test according to genotype or haplotype; P < 0.05 (two-tailed) was considered significant. Because triglyceride levels were not normally distributed, log-transformed values were used for statistical comparison; untransformed mean values are reported here. Analysis of covariance was used to construct a model to explain the variation in triglyceride levels and the overall effect of haplotype on plasma triglyceride levels. Body mass index (BMI), age, smoking, and alcohol consumption were included as covariates, and genotype score was included as a fixed factor in the model (GLM Univariate, SPSS 10.0). The proportion of variation in plasma triglyceride level from each SNP or haplotype was estimated from partial regression coefficients (28Corbex M. Poirier O. Fumeron F. Betoulle D. Evans A. Ruidavets J.B. Arveiler D. Luc G. Tiret L. Cambien F. Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction.Genet. Epidemiol. 2000; 19: 64-80Google Scholar). Chi-square analysis was used to test differences between the observed and expected frequencies of alleles (assuming a Hardy-Weinberg equilibrium) and to compare genotype, allele, or haplotype frequencies after stratification by age- and gender-adjusted triglyceride percentiles (⩽20th and ⩾80th). The expectation-maximization algorithm was used to estimate the maximum-likelihood haplotype frequencies from multilocus genotypic data without known gametic phase (Arlequin software, version 2.00) (29Schneider S. Roessli D. Excoffier L. Arlequin, Ver. 2.000: A Software for Population Genetics Data Analysis. Genetics and Biometry Laboratory, University of Geneva, Switzerland2000http://lgb.unige.ch/arlequin/Google Scholar). All subjects with missing genotype data were excluded during haplotype prediction. Haplotypes that could be unambiguously attributed to individuals were further analyzed for associations with lipid and demographic data. The LD between polymorphisms was similarly calculated with Arlequin (29Schneider S. Roessli D. Excoffier L. Arlequin, Ver. 2.000: A Software for Population Genetics Data Analysis. Genetics and Biometry Laboratory, University of Geneva, Switzerland2000http://lgb.unige.ch/arlequin/Google Scholar) and expressed in terms of D′ = D/Dmax or D/Dmin (30Thompson E.A. Deeb S. Walker D. Motulsky A.G. The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes.Am. J. Hum. Genet. 1988; 42: 113-124Google Scholar). Demographic and biochemical characteristics of 3,020 THS participants are presented in Table 1. Both males and females had low plasma HDL-C levels and high total cholesterol/HDL-C ratios. Detailed analyses of the THS data have been reported (26Mahley R.W. Palaoğlu K.E. Atak Z. Dawson-Pepin J. Langlois A.-M. Cheung V. Onat H. Fulks P. Mahley L.L. Vakar F. et al.Turkish Heart Study. Lipids, lipoproteins, and apolipoproteins.J. Lipid Res. 1995; 36: 839-859Google Scholar, 31Mahley R.W. Pépin J. Palaoğlu K.E. Malloy M.J. Kane J.P. Bersot T.P. Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase: high density lipoprotein characterization and gender-specific effects of apolipoprotein E genotype.J. Lipid Res. 2000; 41: 1290-1301Google Scholar, 32Mahley R.W. Arslan P. Pekcan G. Pépin G.M. Agaçdiken A. Karaagaoglu N. Rakıcıoglu N. Nursal B. Dayanıklı P. Palaoğlu K.E. et al.Plasma lipids in Turkish children: impact of puberty, socioeconomic status, and nutrition on plasma cholesterol and HDL.J. Lipid Res. 2001; 42: 1996-2006Google Scholar). It is noteworthy that low plasma HDL-C levels were found to increase the relative risk for CAD, and the plasma total cholesterol/HDL-C ratio was found to be an independent predictor of coronary events in Turks (33Onat A. Risk factors and cardiovascular disease in Turkey.Atherosclerosis. 2001; 156: 1-10Google Scholar, 34Onat A. Lipids, lipoproteins and apolipoproteins among Turks, and impact on coronary heart disease.Anadolu Kardiyol. Derg. 2004; 4: 236-245Google Scholar). Fifteen SNPs with rare allelic frequencies from <1% to 29% were identified (Table 2). Five SNPs were in the promoter region, including the novel −1021G>A, and one in the 5′ UTR (−3A>G). Four SNPs were in the coding sequence: three were nonsynonymous (S19W, V153M, and G185C) and one was synonymous (I44I). Four SNPs were in the 3′ UTR: two were novel (1387–1388delAG and 1495T>C) and two were published previously (1177C>T and 1259T>C). The IVS3+476G>A intronic SNP was also identified previously.TABLE 2.Description and frequency of APOA5 polymorphisms in TurksPolymorphic SiteaRelative to ATG start, reference sequence AAS68229.1. Synonymous and nonsynonymous changes and their locations are shown in parentheses.Nucleotide ChangeLocation in the GeneLocation on Chromosome 11b(+) strand ENSEMBLE, NCBI build 35, Ch11, 116165297:116167794:1.Rare AlleleNumbercNumber of males/females genotyped by restriction fragment length polymorphism.SNP IdentifierReferencedFirst publication of the particular polymorphism.%−1464T>C≅T/CPromoter−1,456 ≅29.01,574/1,304rs10750097—−1275G>AG/APromoter−1,2679.4129/106rs17120035—−1131T>CT/CPromoter−1,12312.81,601/1,302rs6627998−1099C>TC/TPromoter−1,09110.31,505/1,181rs172941116−1021G>AG/APromoter−1,0125.81,596/1,288New−3A>GA/G5′ UTR613.9230/188rs6518218C56G (S19W)C/GExon 31785.61,633/1,334rs313550620C132A (I44I)C/AExon 32546.1130/107rs1228706620IVS3+ 476G>AG/AIntron 375913.6176/144rs20725608G457A (V153M)G/AExon 41,0974.61,502/1,162rs313550715, 16G553T (G185C)G/TExon 41,1930.6201/288rs207529115, 161177C>TC/T3′ UTR1,8174.5333/272151259T>CT/C3′ UTR1,89914.61,634/1,327rs226678881387–1388delAG(AG)3′ UTR2,027–2,028∼4.613eVariant frequency determined by direct sequencing.New1495T>CT/C3′ UTR2,1354.8136/111NewAPOA5, apolipoprotein A-V gene; SNP, single nucleotide polymorphism; UTR, untranslated region.a Relative to ATG start, reference sequence AAS68229.1. Synonymous and nonsynonymous changes and their locations are shown in parentheses.b (+) strand ENSE" @default.
W2096567265 created "2016-06-24" @default.
W2096567265 creator A5000719244 @default.
W2096567265 creator A5024330806 @default.
W2096567265 creator A5036108557 @default.
W2096567265 creator A5037196802 @default.
W2096567265 creator A5040701823 @default.
W2096567265 date "2006-01-01" @default.
W2096567265 modified "2023-10-11" @default.
W2096567265 title "Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks" @default.
W2096567265 cites W1585035359 @default.
W2096567265 cites W1838268153 @default.
W2096567265 cites W1969725828 @default.
W2096567265 cites W1991845538 @default.
W2096567265 cites W1993385481 @default.
W2096567265 cites W1995897030 @default.
W2096567265 cites W2001677536 @default.
W2096567265 cites W2007542782 @default.
W2096567265 cites W2021445521 @default.
W2096567265 cites W2023466812 @default.
W2096567265 cites W2023907513 @default.
W2096567265 cites W2026234937 @default.
W2096567265 cites W2030058430 @default.
W2096567265 cites W2030069564 @default.
W2096567265 cites W2042486502 @default.
W2096567265 cites W2047138666 @default.
W2096567265 cites W2048814687 @default.
W2096567265 cites W2051973133 @default.
W2096567265 cites W2071347255 @default.
W2096567265 cites W2078074803 @default.
W2096567265 cites W2079460525 @default.
W2096567265 cites W2092521864 @default.
W2096567265 cites W2105912359 @default.
W2096567265 cites W2108361166 @default.
W2096567265 cites W2108836811 @default.
W2096567265 cites W2109811986 @default.
W2096567265 cites W2109947044 @default.
W2096567265 cites W2112582775 @default.
W2096567265 cites W2113481191 @default.
W2096567265 cites W2115371904 @default.
W2096567265 cites W2120259334 @default.
W2096567265 cites W2121528778 @default.
W2096567265 cites W2129741326 @default.
W2096567265 cites W2130663435 @default.
W2096567265 cites W2133140402 @default.
W2096567265 cites W2136248662 @default.
W2096567265 cites W2150281931 @default.
W2096567265 cites W2152528457 @default.
W2096567265 cites W2154292243 @default.
W2096567265 cites W2156425270 @default.
W2096567265 cites W2162588312 @default.
W2096567265 cites W2169934414 @default.
W2096567265 cites W2171101992 @default.
W2096567265 cites W2187846267 @default.
W2096567265 doi "https://doi.org/10.1194/jlr.m500343-jlr200" @default.
W2096567265 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16258166" @default.
W2096567265 hasPublicationYear "2006" @default.
W2096567265 type Work @default.
W2096567265 sameAs 2096567265 @default.
W2096567265 citedByCount "39" @default.
W2096567265 countsByYear W20965672652012 @default.
W2096567265 countsByYear W20965672652013 @default.
W2096567265 countsByYear W20965672652014 @default.
W2096567265 countsByYear W20965672652015 @default.
W2096567265 countsByYear W20965672652016 @default.
W2096567265 countsByYear W20965672652017 @default.
W2096567265 countsByYear W20965672652020 @default.
W2096567265 crossrefType "journal-article" @default.
W2096567265 hasAuthorship W2096567265A5000719244 @default.
W2096567265 hasAuthorship W2096567265A5024330806 @default.
W2096567265 hasAuthorship W2096567265A5036108557 @default.
W2096567265 hasAuthorship W2096567265A5037196802 @default.
W2096567265 hasAuthorship W2096567265A5040701823 @default.
W2096567265 hasBestOaLocation W20965672651 @default.
W2096567265 hasConcept C126322002 @default.
W2096567265 hasConcept C185592680 @default.
W2096567265 hasConcept C2778163477 @default.
W2096567265 hasConcept C2778913445 @default.
W2096567265 hasConcept C2780072125 @default.
W2096567265 hasConcept C55493867 @default.
W2096567265 hasConcept C56623246 @default.
W2096567265 hasConcept C62746215 @default.
W2096567265 hasConcept C71924100 @default.
W2096567265 hasConcept C8243546 @default.
W2096567265 hasConceptScore W2096567265C126322002 @default.
W2096567265 hasConceptScore W2096567265C185592680 @default.
W2096567265 hasConceptScore W2096567265C2778163477 @default.
W2096567265 hasConceptScore W2096567265C2778913445 @default.
W2096567265 hasConceptScore W2096567265C2780072125 @default.
W2096567265 hasConceptScore W2096567265C55493867 @default.
W2096567265 hasConceptScore W2096567265C56623246 @default.
W2096567265 hasConceptScore W2096567265C62746215 @default.
W2096567265 hasConceptScore W2096567265C71924100 @default.
W2096567265 hasConceptScore W2096567265C8243546 @default.
W2096567265 hasIssue "1" @default.
W2096567265 hasLocation W20965672651 @default.
W2096567265 hasOpenAccess W2096567265 @default.
W2096567265 hasPrimaryLocation W20965672651 @default.