Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus

• Published in: Diabetes & metabolism Vol. 37; no. 5; pp. 452 - 455
• Main Authors: Cox, A.J, Wing, M.R, Carr, J.J, Hightower, R.C, Smith, S.C, Xu, J, Wagenknecht, L.E, Bowden, D.W, Freedman, B.I
• Format: Journal Article
• Language: English
• Published: Paris Elsevier Masson SAS 01-11-2011; Masson
• Subjects: African American; African Americans - genetics; African Americans - statistics & numerical data; Aged; Biological and medical sciences; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabète du type 2; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Liver - diagnostic imaging; Fatty Liver - ethnology; Fatty Liver - genetics; Fatty liver disease; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetics; Gène PNPLA3; Génétique; Humans; Internal Medicine; Lipase - genetics; Liver - diagnostic imaging; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Membrane Proteins - genetics; Middle Aged; Non-alcoholic Fatty Liver Disease; North Carolina - epidemiology; Other diseases. Semiology; Polymorphism, Single Nucleotide - genetics; Risk Factors; Stéatohépatite non alcoolique; Sujets afro-américains; Tomography, X-Ray Computed; Type 2 diabetes; Variant rs738409; Type 2 diabetes; Diabète du type 2; Gène PNPLA3; Fatty liver disease; Stéatohépatite non alcoolique; Sujets afro-américains; Génétique; Genetics; Variant rs738409; African American; Endocrinopathy; Digestive system; Liver; Metabolic diseases; Hepatic disease; Density; Variant; Association; Gene; Non alcoholic steatohepatitis; Digestive diseases
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2011.05.001

Abstract Aim Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in patients with obesity and type 2 diabetes mellitus (T2DM), and has been associated with the single nucleotide polymorphism (SNP) rs738409 in the PNPLA3 gene. This association remains to be investigated in African Americans with T2DM, a group at lower risk for hepatic steatosis relative to European Americans with T2DM. Methods We examined 422 African Americans with T2DM (40.3% male; age: 56.4 ± 9.6 years; Body Mass Index: 35.2 ± 8.2 kg/m2 ), all with measures of liver density reflecting hepatic fat content on abdominal computed tomography, and blood glucose and lipid profiles. Associations between rs738409 and phenotypes of interest were determined using SOLAR, assuming an additive model of inheritance with covariates age, sex, BMI and use of lipid-lowering medications. Results Mean ± SD liver density was 55.4 ± 10.2 Hounsfield Units. SNP rs738409 in PNPLA3 was significantly associated with liver density ( P = 0.0075) and hepatic steatosis ( P = 0.0350), but not with blood glucose, HbA1c , total cholesterol, triglycerides, high-density or low-density lipoprotein levels or liver function tests ( P = 0.15–0.96). Conclusion These findings provide evidence that the PNPLA3 SNP rs738409 contributes to risk for increased liver fat content in African Americans with T2DM, an effect that appears to be independent from serum lipids. Although African Americans are less susceptible to fatty liver than European Americans, PNPLA3 appears to be a risk locus for hepatic steatosis in diabetic African Americans.