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• W2052197964 abstract "This study investigates the association of rheumatoid arthritis–associated single nucleotide polymorphisms in endometriosis. We found an association of CCL21 (rs2812378) and HLA-DRB1 (rs660895) with moderate to severe endometriosis. This study investigates the association of rheumatoid arthritis–associated single nucleotide polymorphisms in endometriosis. We found an association of CCL21 (rs2812378) and HLA-DRB1 (rs660895) with moderate to severe endometriosis. Endometriosis is an enigmatic disease mainly affecting women of reproductive age. The plethora of etiologic hypotheses reflects the diversified nature of the disease. In conformity with other complex diseases, a significant genetic contribution could be expected in endometriosis, supported by familial studies that have shown a sixfold to ninefold risk of endometriosis among relatives (1Kennedy S. The genetics of endometriosis.Eur J Obstet Gynecol Reprod Biol. 1999; 82: 129-133Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 2Kennedy S. Bennett S. Weeks D.E. Affected sib-pair analysis in endometriosis.Hum Reprod Update. 2001; 7: 411-418Crossref PubMed Scopus (53) Google Scholar). Several genes, such as tumor necrosis factor (TNF), estrogen receptor-α, and human leukocyte antigen (HLA), have been implicated in the pathogenesis. A substantial number of studies have reported associations of single nucleotide polymorphisms (SNPs) in these genes with endometriosis, although many other studies show the opposite (3Falconer H. D'Hooghe T. Fried G. Endometriosis and genetic polymorphisms.Obstet Gynecol Surv. 2007; 62: 616-628Crossref PubMed Scopus (79) Google Scholar). These contradictory findings are attributed largely to poor study design with small populations and poorly defined ethnicity. In other complex diseases, such as rheumatoid arthritis (RA), clear evidence of genetic contribution has been found. Together with well-established association with HLA-DRB1 variants (4Feitsma A.L. van der Helm-van Mil A.H. Huizinga T.W. de Vries R.R. Toes R.E. Protection against rheumatoid arthritis by HLA: nature and nurture.Ann Rheum Dis. 2008; 67: iii61-iii63Crossref PubMed Scopus (30) Google Scholar, 5Gonzalez-Gay M.A. Garcia-Porrua C. Hajeer A.H. Influence of human leukocyte antigen–DRB1 on the susceptibility and severity of rheumatoid arthritis.Semin Arthritis Rheum. 2002; 31: 355-360Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar), genome-wide association and candidate gene studies have shown associations between several SNPs and RA (6Gregersen P.K. Lee H.S. Batliwalla F. Begovich A.B. PTPN22: setting thresholds for autoimmunity.Semin Immunol. 2006; 18: 214-223Crossref PubMed Scopus (202) Google Scholar, 7Remmers E.F. Plenge R.M. Lee A.T. Graham R.R. Hom G. Behrens T.W. et al.STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus.N Engl J Med. 2007; 357: 977-986Crossref PubMed Scopus (787) Google Scholar), such as protein tyrosine phosphatase, non-receptor type 22 (PTPN22) (8Plenge R.M. Padyukov L. Remmers E.F. Purcell S. Lee A.T. Karlson E.W. et al.Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.Am J Hum Genet. 2005; 77: 1044-1060Abstract Full Text Full Text PDF PubMed Scopus (435) Google Scholar, 9Begovich A.B. Carlton V.E. Honigberg L.A. Schrodi S.J. Chokkalingam A.P. Alexander H.C. et al.A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.Am J Hum Genet. 2004; 75: 330-337Abstract Full Text Full Text PDF PubMed Scopus (1162) Google Scholar), signal transducer and activator of transcription 4 (STAT4) (10Lee H.S. Remmers E.F. Le J.M. Kastner D.L. Bae S.C. Gregersen P.K. Association of STAT4 with rheumatoid arthritis in the Korean population.Mol Med. 2007; 13: 455-460PubMed Google Scholar), TNF receptor–associated factor 1–complement component 5 (TRAF1-C5) (11Plenge R.M. Seielstad M. Padyukov L. Lee A.T. Remmers E.F. Ding B. et al.TRAF1-C5 as a risk locus for rheumatoid arthritis—a genomewide study.N Engl J Med. 2007; 357: 1199-1209Crossref PubMed Scopus (636) Google Scholar), chemokine CC motif ligand 21 (CCL21) (12Raychaudhuri S. Remmers E.F. Lee A.T. Hackett R. Guiducci C. Burtt N.P. et al.Common variants at CD40 and other loci confer risk of rheumatoid arthritis.Nat Genet. 2008; 40: 1216-1223Crossref PubMed Scopus (424) Google Scholar), TNF receptor superfamily member 5/CD40 (12Raychaudhuri S. Remmers E.F. Lee A.T. Hackett R. Guiducci C. Burtt N.P. et al.Common variants at CD40 and other loci confer risk of rheumatoid arthritis.Nat Genet. 2008; 40: 1216-1223Crossref PubMed Scopus (424) Google Scholar), and interferon regulatory factor 5 (IRF5) (13Sigurdsson S. Padyukov L. Kurreeman F.A. Liljedahl U. Wiman A.C. Alfredsson L. et al.Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis.Arthritis Rheum. 2007; 56: 2202-2210Crossref PubMed Scopus (159) Google Scholar). Endometriosis and RA are characterized by chronic inflammation. Introduction of TNF-blocking agents has changed the treatment of RA dramatically (14Maini R.N. Current and new antitumor necrosis factor agents in perspective.Arthritis Res Ther. 2004; 6: S1-S2Crossref PubMed Scopus (7) Google Scholar, 15Toussirot E. Wendling D. The use of TNF-alpha blocking agents in rheumatoid arthritis: an update.Expert Opin Pharmacother. 2007; 8: 2089-2107Crossref PubMed Scopus (72) Google Scholar), and studies performed in nonhuman primates indicate that similar effects could be expected in endometriosis (16D'Hooghe T.M. Nugent N.P. Cuneo S. Chai D.C. Deer F. Debrock S. et al.Recombinant human TNFRSF1A (r-hTBP1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo- and drug-controlled study.Biol Reprod. 2006; 74: 131-136Crossref PubMed Scopus (107) Google Scholar, 17Falconer H. Mwenda J.M. Chai D.C. Wagner C. Song X.Y. Mihalyi A. et al.Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon.Hum Reprod. 2006; 21: 1856-1862Crossref PubMed Scopus (86) Google Scholar). Furthermore, endometriosis fulfills many of the classification criteria for autoimmune disease, including T- and B-cell abnormalities, altered apoptosis, tissue damage and familial occurrence (18Nothnick W.B. Treating endometriosis as an autoimmune disease.Fertil Steril. 2001; 76: 223-231Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 19Matarese G. De Placido G. Nikas Y. Alviggi C. Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?.Trends Mol Med. 2003; 9: 223-228Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar). These similarities suggest that endometriosis could be categorized together with RA, Crohn's disease, systemic lupus erythematosus and related diseases. On the basis of the revised classification system of the American Society for Reproductive Medicine, endometriosis is commonly divided into minimal to mild (stage I–II) or moderate to severe (stage III–IV) disease (20American Society for Reproductive MedicineRevised American Society for Reproductive Medicine classification of endometriosis: 1996.Fertil Steril. 1997; 67: 817-821Abstract Full Text PDF PubMed Scopus (2200) Google Scholar). Recent studies suggest that this subdivision constitutes not only a morphologic difference but also changes in gene expression (21Matsuzaki S. Canis M. Pouly J.L. Botchorishvili R. Dechelotte P.J. Mage G. Differential expression of genes in eutopic and ectopic endometrium from patients with ovarian endometriosis.Fertil Steril. 2006; 86: 548-553Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). However, it is unknown whether these differences result from genomic changes. We hypothesized that the similarities between molecular and cellular pathways of endometriosis and RA implicate a shared genetic background. We therefore investigated the potential association of RA-associated SNPs in endometriosis. Secondarily, genetic differences between stage I–II and III–IV disease were explored. In this study, 1,149 samples (798 patients with endometriosis and 351 controls) were obtained from Caucasian women who had undergone laparoscopy for subfertility with or without pain at the Leuven University Hospital, Leuven, Belgium, during 1998 to 2007. In control patients (aged 32 ± 5 years; body mass index 23.4 ± 4), the absence of endometriosis was confirmed laparoscopically. Women with endometriosis (aged 31 ± 4 years; body mass index 23.2 ± 4) had either minimal (stage I; n = 176), mild (stage II; n = 116), moderate (stage III; n = 88), or severe (stage IV; n = 179) disease, according to American Society for Reproductive Medicine classification (20American Society for Reproductive MedicineRevised American Society for Reproductive Medicine classification of endometriosis: 1996.Fertil Steril. 1997; 67: 817-821Abstract Full Text PDF PubMed Scopus (2200) Google Scholar). Deoxyribonucleic acid from peripheral blood samples and peritoneal biopsies was purified with Chemagic DNA blood special kit (Chemagen, Baesweiler, Germany), AutoPure LS Puregene chemistry (Qiagen,Venlo, Netherlands), manual salting-out procedure (home brew) or Qiagen QIAamp DNA Mini Kit (Qiagen, Hilden, Germany). TaqMan allelic discrimination analyses: CD40 rs4810485 (C_1260190_10), IRF-5 rs3807306 (C_2691231_10), CCL21 rs2812378 (C_16113556_10), STAT-4 rs10181656 (C_30530761_10), TRAF1-C5 rs3761847 (C_2783640_10), PTPN22 rs2476601 (C_16021387_20), HLA-DRB1 rs660895 (C_26546458_30), and HLA-DRB1 rs2395175 (C_16222426_10), were performed according to Applied Biosystems standard protocols (Applied Biosystems, Carlsbad, CA). All TaqMan runs had call rate >95%, and all SNPs were in Hardy-Weinberg equilibrium (<0.05). Associations were analyzed with use of the allelic model with odds ratio and 95% confidence intervals. Bonferroni correction was made, in which obtained P values were multiplied by the number of markers and analysis (× 16). A P value <.05 was considered significant. The study was approved by the Commission for Medical Ethics of the Leuven University Hospital Belgium and the Regional Ethics committee, Karolinska Institute, Stockholm, Sweden. In this large genetic study, we found for the first time an association between CCL21 rs2812378 and moderate to severe endometriosis, before and after Bonferroni correction (P=.0016, vs. P=.0256), seen in Table 1. Interestingly, patients with RA have an increased frequency of the G allele (12Raychaudhuri S. Remmers E.F. Lee A.T. Hackett R. Guiducci C. Burtt N.P. et al.Common variants at CD40 and other loci confer risk of rheumatoid arthritis.Nat Genet. 2008; 40: 1216-1223Crossref PubMed Scopus (424) Google Scholar, 22Orozco G. Eyre S. Hinks A. Ke X. Wilson A.G. Bax D.E. et al.Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study.Ann Rheum Dis. 2010; 69: 813-816Crossref PubMed Scopus (62) Google Scholar), as opposed to the more frequently observed A allele in the current study. Thus, both diseases seem to be associated with variants of the CCL21 gene but with opposite alleles, suggesting a differentiated functional role of the allele. CCL21 is a chemokine, responsible for recruiting CCR7-expressing lymphocytes and dendritic cells to secondary lymphoid tissues (23Cyster J.G. Leukocyte migration: scent of the T zone.Curr Biol. 2000; 10: R30-R33Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar). An in vitro study has shown that CCL21 also costimulates expansion of naïve T-cells and increases secretion of Th1 cytokines, TNF-α and IFN-γ (24Flanagan K. Moroziewicz D. Kwak H. Horig H. Kaufman H.L. The lymphoid chemokine CCL21 costimulates naive T cell expansion and Th1 polarization of non-regulatory CD4+ T cells.Cell Immunol. 2004; 231: 75-84Crossref PubMed Scopus (89) Google Scholar). The potential role of CCL21 in endometriosis is still unknown, although a shift toward a Th1 response may contribute to the increased cytokine/inflammatory profile seen in endometriosis. Endometrial expression of CCL21 is variable according to different phases of the menstrual cycle (25Nakayama T. Kitaya K. Okubo T. Kuroboshi H. Daikoku N. Fushiki S. et al.Fluctuation of 6Ckine expression in human endometrium during the menstrual cycle.Fertil Steril. 2003; 80: 1461-1465Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar) and has been reported to be increased in patients with endometriosis when compared with controls (26Chand A.L. Murray A.S. Jones R.L. Hannan N.J. Salamonsen L.A. Rombauts L. Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis.Reprod Biol Endocrinol. 2007; 5: 18Crossref PubMed Scopus (40) Google Scholar). This observation, together with our data, supports the role of inflammation in the pathogenesis of (moderate to severe) endometriosis.Table 1Distribution of SNP alleles in patients with endometriosis and controls.Genotypes (controls/patients)Allelic modelGeneSNPPatients1/11/22/2MAF (HapMap)MAF controlsMAF patientsP valueaBefore Bonferroni correction.P valuebAfter Bonferroni correction.OR (95% CI)CD40rs4810485 (T/G)All patients23/51129/277185/4450.233 (T)0.260 (T)0.245 (T).4680NS0.9260 (0.7525–1.1396)Stage III and IV23/13129/91185/1550.233 (T)0.260 (T)0.226 (T).1789NS0.8320 (0.6361–1.0882)IRF5rs3807306 (T/G)All patients73/163172/39594/2170.483 (T)0.470 (T)0.465 (T).8663NS0.9846 (0.8217–1.1798)Stage III and IV73/62172/12894/690.483 (T)0.469 (T)0.486 (T).5491NS1.0725 (0.8530–1.3485)CCL21rs2812378 (G/A)All patients38/89170/331134/3570.350 (G)0.360 (G)0.328 (G).1388NS0.8672 (0.7181–1.0474)Stage III and IV38/13170/110134/1260.350 (G)0.360 (G)0.273 (G).0016cSignificant (P<.05)..0256cSignificant (P<.05).0.6689 (0.5202–0.8602)STAT4rs10181656 (G/C)All patients13/37126/260202/4900.217 (G)0.223 (G)0.212 (G).5710NS0.9392 (0.7559–1.1669)Stage III and IV13/11126/94202/1580.217 (G)0.223 (G)0.221 (G).9226NS0.9865 (0.7502–1.2973)TRAF1-C5rs3761847 (G/A)All patients58/130177/403103/2430.483 (A)0.433 (G)0.427 (G).7843NS0.9749 (0.8123–1.1699)Stage III and IV58/45177/138103/790.483 (A)0.433 (G)0.435 (G).9534NS1.0069 (0.7999–1.2674)PTPN22rs2476601 (A/G)All patients2/648/136288/6240.142 (A)0.077 (A)0.097 (A).1374NS1.2832 (0.9227–1.7846)Stage III and IV2/148/42288/2130.142 (A)0.077 (A)0.086 (A).5723NS1.1282 (0.7420–1.7153)HLA-DRB1rs660895 (A/G)All patients11/2676/221249/5320.283 (G)0.146 (G)0.175 (G).0872NS0.8036 (0.6253–1.0328)Stage III and IV11/1576/82249/1680.283 (G)0.146 (G)0.211 (G).0029cSignificant (P<.05)..0464cSignificant (P<.05).0.6372 (0.4725–0.8592)HLA-DRB1rs2395175 (A/G)All patients0/079/224263/5510.233 (A)0.116 (A)0.145 (A).0648NS1.2937 (0.9837–1.7013)Stage III and IV0/079/78263/1840.233 (A)0.116 (A)0.149 (A).0886NS1.3393 (0.9572–1.8740)Note: CI = confidence interval; MAF = minor allele frequency; NS = nonsignificant; OR = odds ratio.a Before Bonferroni correction.b After Bonferroni correction.c Significant (P<.05). Open table in a new tab Note: CI = confidence interval; MAF = minor allele frequency; NS = nonsignificant; OR = odds ratio. Moreover, this study showed association between HLA-DRB1 rs660895 and moderate to severe endometriosis, before and after Bonferroni correction (P=.0029 vs. P=.0464), seen in Table 1. Current understanding of HLA-DRB1 in relation to endometriosis mainly results from studies of Asian populations with relatively small sample sets. Although positive associations have been reported in Japanese populations (27Kitawaki J. Obayashi H. Kado N. Ishihara H. Koshiba H. Maruya E. et al.Association of HLA class I and class II alleles with susceptibility to endometriosis.Hum Immunol. 2002; 63: 1033-1038Crossref PubMed Scopus (22) Google Scholar, 28Ishii K. Takakuwa K. Mitsui T. Tanaka K. Studies on the human leukocyte antigen-DR in patients with endometriosis: genotyping of HLA-DRB1 alleles.Hum Reprod. 2002; 17: 560-563Crossref PubMed Scopus (28) Google Scholar), other studies have found opposing results (29Whang D.H. Kim S.H. Choi Y.M. Park M.H. Noh J.H. Kim Y.B. No association between HLA-DRB1 alleles and susceptibility to advanced stage endometriosis in a Korean population.Hum Reprod. 2006; 21: 129-133Crossref PubMed Scopus (7) Google Scholar, 30Roszkowski P.I. Sankowska M. Jalbrzykowska A. Radomski D. Dragowska K. Ploski R. et al.Susceptibility to ovarian endometriosis in Polish population is not associated with HLA-DRB1 alleles.Hum Reprod. 2005; 20: 970-973Crossref PubMed Scopus (12) Google Scholar). In RA, HLA-DRB1 (rs660895 and rs2395175) has been associated with susceptibility (31Rioux J.D. Goyette P. Vyse T.J. Hammarstrom L. Fernando M.M. Green T. et al.Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases.Proc Natl Acad Sci U S A. 2009; 106: 18680-18685Crossref PubMed Scopus (205) Google Scholar, 32Gonzalez-Recio O. de Maturana E.L. Vega A.T. Engelman C.D. Broman K.W. Detecting single-nucleotide polymorphism by single-nucleotide polymorphism interactions in rheumatoid arthritis using a two-step approach with machine learning and a Bayesian threshold least absolute shrinkage and selection operator (LASSO) model.BMC Proc. 2009; 3: S63Crossref PubMed Google Scholar, 33Jung J. Song J.J. Kwon D. Allelic based gene-gene interactions in rheumatoid arthritis.BMC Proc. 2009; 3: S76Crossref PubMed Google Scholar). However, because the HLA region has a high degree of linkage disequilibrium, it is difficult to establish whether an associated SNP is functional or in linkage disequilibrium with functional SNPs elsewhere. HLA molecules bind antigen and present them to T-cells, with subsequent differentiation into helper or cytotoxic T-cells. Natural killer cells also recognize HLA molecules, leading to inhibition of natural killer cells killing functions. Compared with controls, patients with endometriosis have a reduction of activated T-cells (34Ho H.N. Chao K.H. Chen H.F. Wu M.Y. Yang Y.S. Lee T.Y. Peritoneal natural killer cytotoxicity and CD25+ CD3+ lymphocyte subpopulation are decreased in women with stage III-IV endometriosis.Hum Reprod. 1995; 10: 2671-2675Crossref PubMed Scopus (132) Google Scholar) and defective natural killer cell activity, decreasing in relation to severity of the disease (35Oosterlynck D.J. Cornillie F.J. Waer M. Vandeputte M. Koninckx P.R. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium.Fertil Steril. 1991; 56: 45-51Abstract Full Text PDF PubMed Google Scholar) and decreased levels of circulating HLA class I and class II molecules (36Ota H. Igarashi S. Expression of major histocompatibility complex class II antigen in endometriotic tissue in patients with endometriosis and adenomyosis.Fertil Steril. 1993; 60: 834-838PubMed Scopus (74) Google Scholar). Compared with eutopic endometrium, ectopic endometrium contains an increased proportion of HLA-DR–positive stromal and glandular epithelial cells (36Ota H. Igarashi S. Expression of major histocompatibility complex class II antigen in endometriotic tissue in patients with endometriosis and adenomyosis.Fertil Steril. 1993; 60: 834-838PubMed Scopus (74) Google Scholar, 37Chiang C.M. Hill J.A. Localization of T cells, interferon-gamma and HLA-DR in eutopic and ectopic human endometrium.Gynecol Obstet Invest. 1997; 43: 245-250Crossref PubMed Scopus (48) Google Scholar). Taken together, it is possible that specific types of HLA may be involved in the immunologic changes seen in (moderate to severe) endometriosis. The association between CCL21, HLA-DRB1, and endometriosis was most apparent in moderate to severe disease. Endometriosis is a heterogeneous disease, not only in terms of clinical manifestations but also with respect to morphology and biochemical changes. Different etiologic mechanisms have been proposed (38Nisolle M. Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities.Fertil Steril. 1997; 68: 585-596Abstract Full Text PDF PubMed Scopus (916) Google Scholar), and studies of gene expression have revealed differences between ovarian endometriosis and deep-infiltrating endometriosis, suggesting that local endocrine control and hormonal microenvironment could differ between these types of disease (21Matsuzaki S. Canis M. Pouly J.L. Botchorishvili R. Dechelotte P.J. Mage G. Differential expression of genes in eutopic and ectopic endometrium from patients with ovarian endometriosis.Fertil Steril. 2006; 86: 548-553Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar). Our results indicate that these differences could be explained partly by genetic alterations. The failure to identify disease-specific SNPs may be attributed to the fact that endometriosis in most cases has been considered a uniform phenotype. Definition of the investigated phenotype is of utmost importance in association studies. An illustrating example is RA, in which a subtype of the disease, rheumatoid factor–negative disease, is related to several SNPs (9Begovich A.B. Carlton V.E. Honigberg L.A. Schrodi S.J. Chokkalingam A.P. Alexander H.C. et al.A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.Am J Hum Genet. 2004; 75: 330-337Abstract Full Text Full Text PDF PubMed Scopus (1162) Google Scholar, 13Sigurdsson S. Padyukov L. Kurreeman F.A. Liljedahl U. Wiman A.C. Alfredsson L. et al.Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis.Arthritis Rheum. 2007; 56: 2202-2210Crossref PubMed Scopus (159) Google Scholar). Previous studies have shown contradictory results regarding the association of PTPN22 (rs2476601) and endometriosis. Associations were observed in Italian and Brazilian populations (39Gomes F.M. Bianco B. Teles J.S. Christofolini D.M. de Souza A.M. Guedes A.D. et al.PTPN22 C1858T polymorphism in women with endometriosis.Am J Reprod Immunol. 2010; 63 (227–32)Crossref PubMed Scopus (18) Google Scholar, 40Ammendola M. Bottini N. Pietropolli A. Saccucci P. Gloria-Bottini F. Association between PTPN22 and endometriosis.Fertil Steril. 2008; 89: 993-994Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar), whereas no association was found in a Polish population (41Ploski R. Dziunycz P. Kostrzewa G. Roszkowski P.I. Barcz E. Zabek J. et al.PTPN22/LYP 1858C>T gene polymorphism and susceptibility to endometriosis in a Polish population.J Reprod Immunol. 2009; 79: 196-200Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar). This discrepancy is most likely the result of relatively small study populations. Interestingly, however, in the Brazilian study, association was seen only in women with moderate to severe disease (39Gomes F.M. Bianco B. Teles J.S. Christofolini D.M. de Souza A.M. Guedes A.D. et al.PTPN22 C1858T polymorphism in women with endometriosis.Am J Reprod Immunol. 2010; 63 (227–32)Crossref PubMed Scopus (18) Google Scholar). In this study, with more than 1,000 Caucasian women, no association between PTPN22 and endometriosis was found. It is imperative to point out the importance of sample size (42Colhoun H.M. McKeigue P.M. Davey Smith G. Problems of reporting genetic associations with complex outcomes.Lancet. 2003; 361: 865-872Abstract Full Text Full Text PDF PubMed Scopus (990) Google Scholar). In addition, well-defined ethnicity and careful selection of control groups constitute cornerstones of genetic association studies. It is possible that a susceptibility allele in one ethnic population has no effect in another population, and, therefore, the design of genetic studies needs to be considered carefully and should be taken into consideration when comparing different studies. Taken together, this large genetic study shows association between moderate to severe endometriosis and CCL21 and HLA-DRB1. These findings indicate that there may be different genetic pathways in the pathogenesis of endometriosis, depending on type and severity of the disease. However, it is unlikely that endometriosis shares genetic background with RA. Further studies are needed to validate these polymorphisms in Caucasian women and to shed light on the functional role of disease-associated polymorphisms. Lessons from RA illustrate novel concepts of genetics, many of them applicable to endometriosis research. The authors thank Malin Ermedal, M.D., and Terés Olofsson, M.Sc., at the Department of Women's and Children's Health, Division of Obstetrics and Gynecology, at the Karolinska Institutet for their technical assistance and Gert Matthijs, Ph.D., M.D., Ivo Salden, Tom Janssens, and Cecile Verjauw at the Department of Human Genetics at the Leuven University Hospital, Belgium, for their valuable help." @default.
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• W2052197964 title "Endometriosis and autoimmune disease: association of susceptibility to moderate/severe endometriosis with CCL21 and HLA-DRB1" @default.
• W2052197964 cites W103266845 @default.
• W2052197964 cites W141728048 @default.
• W2052197964 cites W1968868444 @default.
• W2052197964 cites W1977327861 @default.
• W2052197964 cites W1994402720 @default.
• W2052197964 cites W2002237088 @default.
• W2052197964 cites W2003588648 @default.
• W2052197964 cites W2015992070 @default.
• W2052197964 cites W2020766202 @default.
• W2052197964 cites W2021971982 @default.
• W2052197964 cites W2031924019 @default.
• W2052197964 cites W2032350132 @default.
• W2052197964 cites W2035036601 @default.
• W2052197964 cites W2050074853 @default.
• W2052197964 cites W2072650089 @default.
• W2052197964 cites W2077833571 @default.
• W2052197964 cites W2084384313 @default.
• W2052197964 cites W2087635916 @default.
• W2052197964 cites W2098920054 @default.
• W2052197964 cites W2103089222 @default.
• W2052197964 cites W2106631668 @default.
• W2052197964 cites W2109231592 @default.
• W2052197964 cites W2110109352 @default.
• W2052197964 cites W2110377638 @default.
• W2052197964 cites W2118366474 @default.
• W2052197964 cites W2119774152 @default.
• W2052197964 cites W2126781562 @default.
• W2052197964 cites W2131857126 @default.
• W2052197964 cites W2136913354 @default.
• W2052197964 cites W2146176590 @default.
• W2052197964 cites W2147066445 @default.
• W2052197964 cites W2150862288 @default.
• W2052197964 cites W2162276444 @default.
• W2052197964 cites W2164527973 @default.
• W2052197964 cites W2167352050 @default.
• W2052197964 cites W2168781986 @default.
• W2052197964 cites W2170093170 @default.
• W2052197964 cites W2252448738 @default.
• W2052197964 cites W2284066643 @default.
• W2052197964 cites W2416443245 @default.
• W2052197964 cites W2607215535 @default.
• W2052197964 cites W4233594447 @default.
• W2052197964 doi "https://doi.org/10.1016/j.fertnstert.2010.07.1060" @default.
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