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I mpact of leptin receptor gene variants on risk of non‐alcoholic fatty liver disease and its interaction with adiponutrin gene
Author(s) -
Zain Shamsul Mohd,
Mohamed Zahurin,
Mahadeva Sanjiv,
Cheah PhaikLeng,
Rampal Sanjay,
Chin KinFah,
Mahfudz Anis Shafina,
Basu Roma Choudhury,
Tan HwaLi,
Mohamed Rosmawati
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12104
Subject(s) - medicine , leptin receptor , steatohepatitis , fatty liver , allele , odds ratio , endocrinology , leptin , steatosis , genotype , polymorphism (computer science) , gastroenterology , disease , gene , biology , obesity , genetics
Background and Aim 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 . Methods A total of 144 biopsy‐proven NAFLD and 198 controls were genotyped using the Sequenom MassARRAY platform. Results 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). Conclusions 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.