Interactions of smoking with rs۸۳۳۰۶۱ polymorphism on the risk of non-alcoholic fat liver disease in Hubei Han population: a preliminary case–control study

Objective(s):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 -۴۶۰ T/C (rs۸۳۳۰۶۱), and +۹۳۶ C/T (rs۳۰۲۵۰۳۹) polymorphism and risk of non-alcohol fatty liver disease (NAFLD) in Hubei Han population and to further explore the interactions of smoking with rs۸۳۳۰۶۱ and rs۳۰۲۵۰۳۹. Materials and Methods:۳۴۱ healthy controls and ۲۴۶ cases were recruited. Two variants, rs۸۳۳۰۶۱ and rs۳۰۲۵۰۳۹, 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 rs۸۳۳۰۶۱ and rs۳۰۲۵۰۳۹ (ORa=۱.۸۰, ۹۵% confidence interval (CI): ۱.۵۱, ۲.۳۶, Pa=۰.۰۰۰; ORa=۱.۸۹, ۹۵% CI: ۱.۴۱, ۲.۸۲, Pa=۰.۰۰۰, respectively). Interaction of smoking with rs۸۳۳۰۶۱ was found by GMDR, with maximum prediction accuracy (۶۷.۹۱%) and a maximum cross-validation consistency (۱۰/۱۰). ULR method confirmed that, smoking-positive patients with genotype CT/CC had ۴.۹۳ times risk of NAFLD compared to smoking-negative participants with genotype TT (ORadda=۴.۹۳, ۹۵% CI:۲.۹۱, ۸.۵۴, Padda=۰.۰۰۰), which further confirmed synergistic effects. Conclusion: The results indicated that both rs۸۳۳۰۶۱ and rs۳۰۲۵۰۳۹ are associated with NAFLD risk. Furthermore, rs۸۳۳۰۶۱ is likely to have an interaction with smoking, and they have synergistic effects on risk of NAFLD in Hubei Han population.

Keywords:

Interactions , NAFLD , Polymorphisms , Smoking , VEGF