A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease

• DOI: 10.1007/s00439-012-1141-y
• Publication Date: 2012-01-18T04:10:37Z
• Authors: Shamsul Mohd Zain; Rosmawati Mohamed; Sanjiv Mahadeva; Phaik Leng Cheah; Sanjay Rampal; Roma Choudhury Basu; Zahurin Mohamed
• Keywords: Liver Cirrhosis; Male; 0301 basic medicine; Genotype; 610; R Medicine; Polymorphism, Single Nucleotide; Body Mass Index; 03 medical and health sciences; Gene Frequency; Non-alcoholic Fatty Liver Disease; Genetics; Humans; Genetics(clinical); Genetic Predisposition to Disease; Alleles; Triglycerides; Original Investigation; Genetic Variation; Membrane Proteins; Lipase; Middle Aged; 3. Good health; Fatty Liver; Liver; Case-Control Studies; Female

The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.