Original Investigation

Human Genetics

, Volume 131, Issue 7, pp 1145-1152

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Shamsul Mohd ZainAffiliated withThe Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya Email author 
  • , Rosmawati MohamedAffiliated withDepartment of Medicine, Faculty of Medicine, University of Malaya
  • , Sanjiv MahadevaAffiliated withDepartment of Medicine, Faculty of Medicine, University of Malaya
  • , Phaik Leng CheahAffiliated withDepartment of Pathology, Faculty of Medicine, University of Malaya
  • , Sanjay RampalAffiliated withDepartment of Social and Preventive Medicine, Faculty of Medicine, Julius Centre University of Malaya, University of Malaya
  • , Roma Choudhury BasuAffiliated withClinical Investigation Centre, University Malaya Medical Centre
  • , Zahurin MohamedAffiliated withThe Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya Email author 

Abstract

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 occurence of fibrosis in patients with NAFLD.