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I148 M variant in PNPLA 3 reduces central adiposity and metabolic disease risks while increasing nonalcoholic fatty liver disease
Author(s) -
Park JinHo,
Cho BeLong,
Kwon Hyuktae,
Prilutsky Daria,
Yun Jae Moon,
Choi Ho Chun,
Hwang KyuBaek,
Lee InHee,
Kim JongIl,
Kong Sek Won
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12909
Subject(s) - steatosis , medicine , nonalcoholic fatty liver disease , fatty liver , gastroenterology , insulin resistance , odds ratio , endocrinology , disease , obesity
Background & Aims The I 148 M variant because of the substitution of C to G in PNPLA 3 (rs738409) is associated with the increased risk of nonalcoholic fatty liver disease ( NAFLD ). In liver, I 148 M variant reduces hydrolytic function of PNPLA 3, which results in hepatic steatosis; however, its association with the other clinical phenotype such as adiposity and metabolic diseases is not well established. Methods To identify the impact of I 148 M variant on clinical risk factors of NAFLD , we recruited 1363 generally healthy K orean males after excluding alcoholic and secondary causes of hepatic steatosis. Central adiposity was assessed by computed tomography, and hepatic steatosis was evaluated by abdominal ultrasonography. Results The participants were predominantly middle‐aged (49.0 ± 7.1 years; range 30–60 years), and the frequency of NAFLD was 44.2%. The rs738409‐ G allele carriers had a 1.19‐fold increased risk for NAFLD (minor allele frequency 0.43; allelic odds ratio 1.38; P = 4.3 × 10 −5 ). Interestingly, the rs738409 GG carriers showed significantly lower levels of visceral and subcutaneous adiposity ( P < 0.001 and = 0.015, respectively), BMI ( P < 0.001), triglycerides ( P < 0.001) and insulin resistance ( P = 0.002) compared to CC carriers. These negative associations between clinical risk factors and rs738409‐ G dosage were more prominent in non‐ NAFLD group compared to those in NAFLD group. Conclusions The I 148 M variant, although increasing the risk of NAFLD , was associated with reduced levels of central adiposity, BMI , serum triglycerides and insulin resistance, suggesting differential roles in fat storage and distribution according to cell types and metabolic status.