Association between TM6SF2 rs58542926 polymorphism and non-alcoholic fatty liver disease in Qingdao Han population and molecular mechanism / 解放军医学杂志

ABSTRACT

Objective To investigate the association between the TM6SF2 rs58542926 polymorphism and non-alcoholic fatty liver disease (NAFLD) in Qingdao Han Population, and the molecular mechanism of TM6SF2 167 locus polymorphism affecting lipid metabolism. Methods We genotyped a cohort of NAFLD patients (NAFLD group) treated in Qingdao Municipal Hospital from Octorber 2016 to November 2017 and 451 healthy controls (control group) matched for age and sex by polymerase chain reaction and direct sequencing. Distribution of genotypes and allele frequencies of TM6SF2 rs58542926 and the relative risk of NAFLD were assessed. In addition, we concentrated the lentivirus of TM6SF2-mutant type and TM6SF2-wild type and transfected into Hepa1-6 cells. The concentration of lipid indicators and the expressions of SREBP-1c mRNA and protein were determined. Results There were significant differences in the genotype and allele frequencies of TM6SF2 rs58542926 polymorphism between the NAFLD and control group (P<0.001). Carriers of T allele had significantly increased susceptibility to NAFLD (OR=2.327, 95%CI: 1.542-3.513, P<0.001). Total cholesterol (TC) and triglyceride (TG) contents of the TM6SF2-mutant type group were both increased to high levels when compared with the TM6SF2-wild type group (P<0.001). Furthermore, the expression levels of sterol regulatory element-binding transcription factor 1c (SREBP-1c) mRNAs and protein of the TM6SF2-mutant type group were significantly increased when compared with either of the TM6SF2-wild type group (P<0.001). Conclusions The TM6SF2 rs58542926 polymorphism is associated with risk of NAFLD in Qingdao Han Population. Furthermore, the mutant T allele at TM6SF2 167 locus may regulate the hepatic lipid metabolism through increasing the expression of SREBP-1c.