Objective  To explore the association of G > A variation in promoter region-2548 of leptin gene (LEP G2548A) and generelevant factor interaction with nonalcoholic fatty liver disease (NAFLD) in Chinese population.

  Methods  A total of 200 cases of NAFLD were recruited from health examinees at a general hospital in Xiamen city between March 2015 and February 2016 and 400 gender- and age-matched (1:2) controls were enrolled simultaneously. Genotyping for single nucleotide polymorphisms (SNPs) of LEP G2548A was conducted with LightCycler480 PCR platform using high resolution melting (HRM) approaches and the detection results were then validated through direct sequencing. Chi-square test was used to evaluate the correlation between SNPs of LEP G2548A and NAFLD; univariate and multivariate logistic regression were applied to explore relevant factors of NAFLD; and crossover analysis was adopted to assess interactive effects of LEP G2548A mutation and relevant risk factors.

  Results  The results of multivariate conditional logistic regression revealed that high serum total cholesterol (TC), leptin, and fasting blood glucose (FBG) and smoking were the risk factors of NAFLD, with the odds ratio (OR) (95% confidence interval 95% CI) of 1.609 (1.104 – 2.347), 1.510 (1.025 – 2.224), and 2.381 (1.182 – 4.797) and 1.717 (1.074 – 2.748), respectively. However, keeping frequent physical exercise was a protection factor against NAFLD (OR = 0.666, 95% CI: 0.461 – 0.961). Crossover analysis indicated that the participants with AA type of LEP G2548A were at a higher risk of NAFLD when having a high level of serum LEP (OR = 2.247, 95% CI:1.349 – 3.743) or FBG (OR = 4.202, 95% CI:1.810 – 9.755), suggesting significantly positive interactions between G > A mutation of LEP G2548A and serum LEP and FBG (both P < 0.01).

  Conclusion  High serum leptin level, AA genotype and A allele of LEP G2548A are risk factors of NAFLD, and the interaction between SNPs of LEP G2548A and serum leptin and FBG level increases the risk of NAFLD.