Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene

Cheah, P.L. and Zain, S.M. and Mohamed, Z. and Mahadeva, S. and Rampal, S. and Chin, K.F. and Mahfudz, A.S. and Basu, R.C. and Tan, H.L. and Mohamed, R. (2013) Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene. Journal of Gastroenterology and Hepatology, 28 (5). pp. 873-9. ISSN 0815-9319

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Abstract

Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor(LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3(PNPLA3/adiponutrin) are associated with risk of NAFLD.A total of 144 biopsy-proven NAFLD and 198 controls were genotyped using the Sequenom MassARRAY platform. We observed a significant association between the LEPR rs1137100 and rs1137101 with susceptibility to NAFLD (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.18-2.28, P = 0.003; and OR 1.61, 95% CI 1.11-2.34, P = 0.013, respectively) and to non-alcoholic steatohepatitis (OR 1.49,95% CI 1.05-2.12, P = 0.026; and OR 1.57, 95% CI 1.05-2.35, P = 0.029, respectively). The LEPR rs1137100 is also associated with simple steatosis (OR 2.27, 95% CI 1.27-4.08, P = 0.006). Analysis of gene-gene interaction revealed a strong interaction between the LEPR and PNPLA3 genes(empirical P = 0.001). The joint effect of LEPR and PNPLA3 greatly exacerbated the risk of NAFLD(OR 3.73, 95% CI 1.84-7.55, P < 0.0001). The G allele of rs1137100 is associated with lower fibrosis score (OR 0.47, 95% CI 0.28-0.78, P = 0.001).We report an association between variants of LEPR rs1137100 and rs1137101 with risk of NAFLD. This study suggests that rs1137100, specifically the G allele, is associated with a less severe form of liver disease in patients with NAFLD. The interaction between LEPR and PNPLA3 genes showed increased risk of NAFLD compared to either gene alone.

Item Type: Article
Additional Information: The Pharmacogenomics Laboratory, Department of Pharmacology, University of Malaya
Uncontrolled Keywords: Non-alcoholic fatty liver disease; leptin receptor gene; adiponutrin gene
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Suhaila Syakila Alby
Date Deposited: 20 Oct 2014 03:15
Last Modified: 21 Dec 2014 08:01
URI: http://eprints.um.edu.my/id/eprint/10065

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