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- Title
Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene.
- Authors
Zain, Shamsul Mohd; Mohamed, Zahurin; Mahadeva, Sanjiv; Cheah, Phaik‐Leng; Rampal, Sanjay; Chin, Kin‐Fah; Mahfudz, Anis Shafina; Basu, Roma Choudhury; Tan, Hwa‐Li; Mohamed, Rosmawati
- Abstract
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.
- Subjects
LEPTIN receptors; FATTY liver; LIVER diseases; PHOSPHOLIPASES; GENETIC polymorphisms; GENETICS
- Publication
Journal of Gastroenterology & Hepatology, 2013, Vol 28, Issue 5, p873
- ISSN
0815-9319
- Publication type
Academic Journal
- DOI
10.1111/jgh.12104