Association Of GRK5 Rs10886471 Polymorphism With Non-alcoholic Fatty Liver Disease And Coronary Atherosclerotic Heart Disease

Objective:The rs10886471 polymorphism of G protein coupled receptor kinase 5(GRK5)is associated with the risk of type 2 diabetes mellitus(T2DM)in a Chinese Han population.There are currently no studies on the association of GRK5 rs10886471 polymorphism with non-alcoholic fatty liver disease(NAFLD)and coronary atherosclerotic heart disease(CAD).In this paper,we aimed to analyze the association between GRK5 rs10886471 polymorphism and NAFLD and CAD.Methods:Methods:(1)grouping situation: a total of 656 individuals were included in this study and divided into four groups: 144 subjects in the NAFLD group;255 healthy control subjects;147 subjects in the CAD group;110 subjects in the NAFLD + CAD(NAFLD combined with CAD)group.The NAFLD + CAD group was divided into 2 groups: 75 subjects from the G0 group(mild fatty liver group);35 G1 group(moderate severe fatty liver group)subjects.(2)Information was collected: basic information from questionnaires,body mass index(BMI)was calculated by measuring height weight;Biochemical indexes: a fasting venous blood sample was drawn to detect renal function: to the indexes are fasting plasma glucose(FPG),lipid levels: to the indexes are total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),Liver function: the indicators used were alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamine transpeptidase(GGT),alkaline phosphatase(AFP),total bilirubin(TBIL);DNA extraction and genotyping: GRK5 rs10886471 was genotyped by polymerase chain reaction.(3)Data analysis: with SPSS 23.0 statistical software.Methods of analysis between groups used were chi square,t-test,or nonparametric,and logistic regression models were used to correct for confounders and to analyze associations.P < 0.05 indicated that the data were statistically significant.Results:(1)Age,BMI,FPG,TC,TG,HDL,LDL,ALT,GGT,ALP were the indicators that were statistically different between the healthy control,NAFLD,CAD and NAFLD + CAD groups(all P < 0.05).There was a statistical difference in BMI between the G0 and G1groups(P < 0.05).(2)The healthy control,NAFLD and CAD groups were compared with the NAFLD + CAD group(healthy control vs NAFLD + CAD,NAFLD vs NAFLD + CAD,and CAD vs NAFLD + CAD),and statistically significant differences were observed between genotype distributions and allele frequencies(all P < 0.05).In the comparison between the G0 and G1 groups,there were significant differences in the genotype distribution and allele frequencies(all P < 0.05).(3)The minor allele(T)was a risk factor for the development of NAFLD combined with CAD in the three groups: healthy controls,NAFLD and CAD(all OR > 1,P < 0.05).After adjusting for confounders(age,gender and BMI),in a recessive genetic model for T,the TT genotype was a risk factor for the development of NAFLD combined with CAD in healthy controls group(OR = 3.616,95% CI: 1.152-11.348,P = 0.028);In the dominant genetic model of T,TT + TC were risk factors for NAFLD in CAD group(OR = 2.340,95% CI: 1.356-4.037,P = 0.002).(4)The minor allele(T)was a risk factor for the development of moderate to severe fatty liver in the G0 group(OR = 1.989,95% CI: 1.186-3.338,P = 0.009).After adjusting for confounders(age,gender and BMI),the TT + TC genotype was a risk factor for progression to moderate to severe fatty liver disease in G0 group under the dominant genetic model of T(OR = 3.318,95% CI: 1.409-7.813,P = 0.006).(5)In healthy controls,the TT / TC genotype of GRK5 rs10886471 had higher BMI,TC and LDL levels than the CC genotype(all P < 0.05,OR > 1).After adjusting for confounding factors(age,gender),the levels of BMI,TC and LDL of TT / TC genotype were still higher than those of CC genotype,and the differences were statistically significant(all P < 0.05,OR > 1).Conclusion:(1)The T allele of GRK5 rs10886471 was associated with the risk of NAFLD with CAD in the healthy population and with the risk of NAFLD in the CAD population.(2)The T allele of GRK5 rs10886471 was associated with the risk of progression from mild fatty liver to moderate severe fatty liver in the NAFLD with CAD population.(3)The GRK5 rs10886471 T allele was associated with increased BMI,TC and LDL levels in healthy individuals.