title: Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene.
abstract: OBJECTIVE
  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.
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. soulz712@gmail.com
authors.forename: Shamsul Mohd
authors.initials: SM
authors.lastname: Zain
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Mahadeva
authors.forename: Phaik-Leng
authors.initials: PL
authors.lastname: Cheah
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rampal
authors.forename: Kin-Fah
authors.initials: KF
authors.lastname: Chin
authors.forename: Anis Shafina
authors.initials: AS
authors.lastname: Mahfudz
authors.forename: Roma Choudhury
authors.initials: RC
authors.lastname: Basu
authors.forename: Hwa-Li
authors.initials: HL
authors.lastname: Tan
authors.forename: Rosmawati
authors.initials: R
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D004198:Disease Susceptibility; D004843:Epistasis, Genetic / Q000235:genetics*; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011110:Polymorphism, Genetic; D054411:Receptors, Leptin / Q000235:genetics*; D012306:Risk
chemical_list: D008565:Membrane Proteins; D054411:Receptors, Leptin; C436316:adiponutrin