Association Bewteen TRIB1 Rs17321515 And Rs2954029 Gene Polymorphisms And Non-alcoholic Fatty Liver Disease

Background:Non-alcoholic fatty liver disease(NAFLD)has become the world's largest liver disease and a common cause of chronic aminotransferase elevations and cirrhosis.The pathogenesis of NAFLD is not clear.At present,the"second hits"hypothesis and the"multiple parallel"hypothesis are widely accepted.Numerous studies have shown that genetic susceptibility exerts an active role in the occurrence and progress of NAFLD.Currently,more researches are on transmembrane 6 superfamily member 2(TM6SF2)and patatin-like phospholipase domain-containing protein 3(PNPLA3).The study of genetic susceptibility provides new perspectives and ideas for the diagnosis and treatment of NAFLD.Tribbles homotog1(TRIB1)encodes tribbles protein,which belongs to pseudokinase.Foreign scholars have confirmed that the TRIB1 gene polymorphism is related to circulating blood lipid levels,but the correlation between the TRIB1 gene polymorphisms and NAFLD susceptibility and circulating blood lipid levels in the Han population have not been reported.Objective:Among the Han population,we attempted to investigate the association between TRIB1 rs17321515 and rs2954029 gene polymorphisms and the risk of developing NAFLD in the Qingdao population,and to test the effect of TRIB1 gene polymorphisms on serum lipid levels.Methods:In Qingdao Municipal Hospital from June 2018 to February 2019,a total of 200 NAFLD patients and 230 healthy controls were selected.Fasting venous blood was collected and averagely put into two EDTA anticoagulant tubes,one was sent for the detection of biochemical test kit,and the other was later used for the genotype determination of TRIB1 rs17321515 and rs2954029.Genotype determination included steps such as primer design and synthesis,DNA extraction,PCR amplification reaction,product alkaline phosphatase treatment,single base extension reaction,resin purification,chip spotting,and mass spectrometry detection.The Hardy-Weinberg equilibrium and comparison of categorical data between groups were tested by the chi-square test.The comparison of continuous data between two groups were tested by t-test.Binary logistic regression model was used to estimated the association between TRIB1 rs17321515 and rs2954029 gene polymorphisms and the relative risk of developing NAFLD,through computing odds ratio(OR)and its 95%confidence interval(CI).Results:Three genotypes of GG,GA and AA were found in TRIB1 rs17321515,and three genotypes of TT,TA and AA were found in rs2954029.The genotype distributions and allele distributions of TRIB1 rs17321515 and rs2954029 were significantly different between the NAFLD patients and healthy controls(genotype distributions of rs17321515:?~2=8.527,P=0.014;allele distributions of rs17321515:?~2=9.150,P=0.002;genotype distributions of rs2954029:?~2=7.339,P=0.025;allele distributions of rs2954029:?~2=7.556,P=0.006).The results analyzed by the logistic regression model showed that TRIB1 rs17321515 GA+AA genotype and TRIB1 rs2954029 TA+AA genotype markedly increase the NAFLD risk(OR=1.714,95%CI:1.142?2.537,P=0.009;OR=1.664,95%CI:1.106?2.503,P=0.015,respectively),after adjusting for age and gender,the NAFLD risk was still significant(OR=1.988,95%CI:1.164?3.394,P=0.008;OR=1.924,95%CI:1.149?3.221,P=0.013,respectively).In addition,TRIB1rs17321515 A carriers possessed higher BMI,serum TC and TG levels(P<0.05).TRIB1rs2954029 A carriers possessed higher serum FPG and LDL levels(P<0.05).Conclusion:In the Han population,TRIB1 rs17321515 A allele and rs2954029 A allele increase the risk of developing NAFLD;the TRIB1 rs17321515 A allele carriers possess higher BMI and higher serum TC and TG levels;the TRIB1 rs2954029 A allele carriers possess higher serum FPG and LDL levels.