Genetic variants in promoter region of TFR2 is associated with the risk of non-alcoholic fatty liver disease in a Chinese Han population: A case-control study

Abstract

Background: Iron overload is frequently observed in non-alcoholic fatty liver disease (NAFLD). Transferrin receptor 2 (TFR2) is an important key factor in iron regulation. We aimed to investigate whether TFR2 single nucleotide polymorphisms (SNPs) contribute to susceptibility to NAFLD in a Chinese Han population. Methods: Five tag SNPs (rs10247962, rs4434553, rs2075672, rs1052897, and rs3757859) in the TFR2 gene were selected and genotyped in a case-control study on participants who visited two affiliated hospitals of Fujian Medical University between June 2011 and August 2017. Propensity score matching and inverse probability of treatment weighting analyses were used to verify the risk associated with TFR2 SNPs. Results: Logistic regression analyses suggested that subjects with the rs4434553 GA or GG genotype had a lower risk of NAFLD than those carrying the AA genotype (odds ratio = 0.630, 95% confidence interval = 0.504-0.788). Moreover, the rs4434553 GA or GG genotype was negatively correlated with body mass index, hepatic steatosis index, and serum ferritin (b =-0.363, P = 0.008; b =-1.040, P = 0.009; b =-35.258, P = 0.015, respectively), and positively associated with serum hepcidin level (b = 35.308, P < 0.001). Moreover, rs10247962 and rs1052897 had multiplicative interactions with age in relation to the risk of NAFLD (P for interactions, 0.041 and 0.034, respectively). The cumulative effects of the rs10247962, rs1052897, and rs4434553 SNPs were positively associated with the risk of NAFLD (adjusted Ptrend = 0.012). Conclusions: In this Chinese Han population, the rs4434553 polymorphism in TFR2 may be an independent influencing factor associated with the susceptibility to NAFLD. The ageing effect on the development of NAFLD may be inhibited by SNPs rs10247962 and rs1052897.