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

Zain, Shamsul Mohd and Mohamed, Rosmawati and Mahadeva, Sanjiv and Cheah, Phaik Leng and Rampal, Sanjay and Basu, Roma Choudhury and Mohamed, Zahurin (2012) A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Human Genetics, 131 (7). pp. 1145-1152. ISSN 0340-6717, DOI https://doi.org/10.1007/s00439-012-1141-y.

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Official URL: https://doi.org/10.1007/s00439-012-1141-y


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. © 2012 The Author(s).

Item Type: Article
Uncontrolled Keywords: Adiponutrin; liver protein; unclassified drug; adult; allele; blood sampling; Polymorphism; Single Nucleotide; Triglycerides
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms Haslinda Lahuddin
Date Deposited: 07 Mar 2013 04:12
Last Modified: 08 Feb 2021 07:53
URI: http://eprints.um.edu.my/id/eprint/5032

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