A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity

作者：Leon Mimila Paola; Vega Badillo Joel; Gutierrez Vidal Roxana; Villamil Ramirez Hugo; Villareal Molina Teresa; Larrieta Carrasco Elena; Lopez Contreras Blanca E; Macias Kauffer Luis R; Maldonado Pintado Diana G; Mendez Sanchez Nahum; Tovar Armando R; Hernandez Pando Rogelio; Velazquez Cruz Rafael; Campos Perez Francisco; Aguilar Salinas Carlos A; Canizales Quinteros Samuel^*

来源：Experimental and Molecular Pathology, 2015, 98(2): 178-183.

DOI：10.1016/j.yemp.2015.01.012

• Liver fat content
• NASH
• NAFLD
• Polymorphisms
• GRS

Background and aims: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near/in PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes associated with non-alcoholic fatty liver disease (NAFLD) mainly in individuals of European ancestry. The aim of the study was to test whether these genetic variants and a genetic risk score (GRS) are associated with elevated liver fat content and non-alcoholic steatohepatitis (NASH) in Mexicans with morbid obesity.
Methods: 130 morbidly obese Mexican individuals were genotyped for six SNPs in/near PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes. Hepatic fat content [triglyceride (HTG) and total cholesterol (HTC)] was quantified directly in liver biopsies and NASH was diagnosed by histology. A GRS was tested for association with liver fat content and NASH using logistic regression models. In addition, 95 ancestry-informative markers were genotyped to estimate population admixture proportions.
Results: After adjusting for age, sex and admixture, PNPLA3, LYPLAL1, GCKR and PPP1R3B polymorphisms were associated with higher HTG content (P < 0.05 for PNPLA3, LYPLAL1, GCKR polymorphisms and P = 0.086 for PPP1R3B). The GRS was significantly associated with higher HTG and HTC content (P = 1.0 x 10(-4) and 0.048, respectively), steatosis stage (P = 0.029), and higher ALT levels (P = 0.002). Subjects with GRS >= 6 showed a significantly increased risk of NASH (OR = 2.55, P = 0.045) compared to those with GRS <= 5. However, the GRS did not predict NASH status, as AUC of ROC curves was 0.56 (P = 0219).
Conclusion: NAFLD associated loci in Europeans and a GRS based on these loci contribute to the accumulation of hepatic lipids and NASH in morbidly obese Mexican individuals.

• 出版日期2015-4