title: Interactions of smoking with rs833061 polymorphism on the risk of non-alcoholic fat liver disease in Hubei Han population: a preliminary case-control study.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) has biological actions on energy homeostasis, inflammation and insulin resistance. The present study aimed to investigate the association between VEGF -460 T/C (rs833061), and +936 C/T (rs3025039) polymorphism and risk of non-alcohol fatty liver disease (NAFLD) in Hubei Han population and to further explore the interactions of smoking with rs833061 and rs3025039.
  
  
  METHODS
  341 healthy controls and 246 cases were recruited. Two variants, rs833061 and rs3025039, were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The unconditional logistic regression (ULR) was performed to assess the association of the two variants with risk of NAFLD. Gene-environment interactions on the risk of NAFLD were preliminarily explored by generalized multifactor dimensionality reduction (GMDR) and further confirmed by ULR methods.
  
  
  RESULTS
  After adjusting for covariates, increased risk of NAFLD was observed in patients carrying CT/CC genotypes in rs833061 and rs3025039 (ORa=1.80, 95% confidence interval (CI): 1.51, 2.36, Pa =0.000; ORa=1.89, 95% CI: 1.41, 2.82, Pa =0.000, respectively). Interaction of smoking with rs833061 was found by GMDR, with maximum prediction accuracy (67.91%) and a maximum cross-validation consistency (10/10). ULR method confirmed that, smoking-positive patients with genotype CT/CC had 4.93 times risk of NAFLD compared to smoking-negative participants with genotype TT (ORadd (a)=4.93, 95% CI: 2.91, 8.54, P add (a)=0.000), which further confirmed synergistic effects.
  
  
  CONCLUSIONS
  The results indicated that both rs833061 and rs3025039 are associated with NAFLD risk. Furthermore, rs833061 is likely to have an interaction with smoking, and they have synergistic effects on risk of NAFLD in Hubei Han population.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang Road, Wuhan, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Tongcheng, Minzhu Road 120, Hubei, China.
authors.forename: Yonglong
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang Road, Wuhan, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang Road, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang Road, Wuhan, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yongxiang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang Road, Wuhan, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Fang
keywords: Interactions; NAFLD; Polymorphisms; Smoking; VEGF