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- W3092735268 abstract "Abstract Context The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. Objective To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. Design Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids and lipoproteins in 2 cohorts, both divided into groups based on rs738409-G allele carrier status and median HOMA-IR. Setting Tertiary referral center. Patients A total of 298 obese patients who underwent a liver biopsy during bariatric surgery (bariatric cohort: age 49 ± 9 years, body mass index [BMI] 43.2 ± 6.8 kg/m2), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort: age 45 ± 14 years, BMI 29.7 ± 5.7 kg/m2). Main Outcome Measures Nuclear magnetic resonance profiling of plasma lipids, lipoprotein particle subclasses and their composition. Results In both cohorts, individuals carrying the PNPLA3-I148M variant had significantly higher liver fat content than noncarriers. In insulin-resistant and homozygous carriers, PNPLA3-I148M exerted a distinct antihyperlipidemic effect with decreased very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles and their constituents, and increased high-density lipoprotein particles and their constituents, compared with noncarriers. VLDL particles were smaller and LDL particles larger in PNPLA3-I148M carriers. These changes were geometrically opposite to those due to IR. PNPLA3-I148M did not have a measurable effect in patients with lower IR, and its effect was smaller albeit still significant in the less obese than in the obese cohort. Conclusions PNPLA3-I148M confers an antiatherogenic plasma lipid profile particularly in insulin-resistant individuals." @default.
- W3092735268 created "2020-10-22" @default.
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- W3092735268 date "2020-10-16" @default.
- W3092735268 modified "2023-10-16" @default.
- W3092735268 title "The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients" @default.
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- W3092735268 doi "https://doi.org/10.1210/clinem/dgaa729" @default.
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