Association Between Sort1 Gene Rs646776 Polymorphisms With Non-alcoholic Fatty Liver Disease

Background:Nonalcoholic fatty liver disease(NAFLD)is an increasingly serious medical problem around the world and may develop into cirrhosis and hepatocellular carcinoma.In order to clarify the prevention and treatment of NAFLD,It is of great important clinical significance to research the pathogenesis of NAFLD.At present,the incidence of NAFLD is the result of multiple factors,in which genetic factors play an important role.Sorting protein 1(Sort1)is a lipid metabolism regulatory gene,which encodes sortilin that is the intracellular receptor of apolipoprotein.The polymorphism of Sort1 gene has been proved to be related to lipid metabolism,but there is still no correlation between Sort1 and NAFLD.Objective:To investigate the effect of Sort1 single nucleotide polymorphism(SNP)rs646776 gene polymorphism on serum lipid levels and its association with the risk of NAFLD.Methods:This study is based on a case control study of Han nationality in northern china.Blood samples were collected from the Qingdao Municipal Hospital of 294 NAFLD patients and 296 normal person,and given them to the biotechnology company for gene testing of Sort1 rs646776.The Hardy-Weinberg equilibrium(H-W)method was used to analysis whether the genotype of the case group and the control group were representative.The clinical and serum biochemical indexes of the two groups were measured.The differences of clinical data between NAFLD group and normal control group,genotype and allele frequencies of Sort1 rs646776 were compared.In this study,the statistical analysis package SPSS 20.0 was used for the statistical analysis.Pearson chi-square test and t test were used to compare counting data and measurement data respectively.The odds ration(OR)and 95%confidence interval(95%CI)was calculated via the non conditional logistic regression analysis.Results:The age,BMI and blood pressure of NAFLD group were higher than those of control group(P<0.05).In the laboratory examination,ALT,AST,GGT,ALP,FPG,TG,TC and LDL in NAFLD group were higher than those in control group,the difference was statistically significant(P<0.05);HDL was lower than the control group,the difference was statistically significant(P<0.05).There were significant differences in the frequencies of rs646776 genotype and allele between the NAFLD and control subjects(?2=5.389,P=0.020;?2=6.572,P=0.037).Non conditional Logistic regression analysis showed that in contrast with C allele,there was an increased risk of NAFLD for rs646776 T allele(OR=1.521,95%CI:1.089?2.123,P=0.014).Logistic regression analysis adjusted for confounding factors(just like gender,age,body mass index and so on)showed that the risk of T allele with NAFLD is 1.443 times higher than that of C allele carriers(OR=1.443,95%CI=0.812?2.564,P>0.05),no statistical significance.In the combined population,CC genotype had higher HDL-C level(P=0.000)than the TC/TT genotype,and had lower TG level(P=0.042).The level of TC+TT in HDL-C was higher than that of TG(P=0.000;P=0.030).Conclusion:The polymorphism of Sort1 gene rs646776 is associated with serum lipid levels,but is not associated with the risk of NAFLD in northern Chinese Han population.