Association Between Polymorphisms Of MTHFR,MTRR Gene And Nonalcoholic Fatty Liver Disease In Uygur Population Of Xinjiang

Objective: To correlate the relationship between Methylenetetrahydrofolate reductase(MTHFR)and methionine synthase reductase(MTRR)genes polymorphism withand non-alcoholic fatty liver disease(NAFLD)in Uygurs.Methods: 325 cases of NAFLD patients were recruited in NAFLD group and 325 healthy examination individuals were selected as control.Clinical data and blood sample were collected from each subject,genomic DNA was extracted from whole peripheral blood leukocytes.The MTHFR,MTRR gene polymorphism was detected by improved multiple ligase detection reaction(iMLDR).We analyse the relationship between susceptibility to NAFLD and different genotypes.Results: 1)The weight,WC,SBP,DBP,BMI,WHtR of the NAFLD group were higher than those of the control group,the difference was statistically significant(P<0.05).2)The levels of ALT、TC、AST、TG、FPG、LDL-C、UA、HbA1c were higher than the control group,the difference was statistically significant(P<0.05).3)NAFLD group and control group,there were significant differences in the incidence of hypertension,diabetes and coronary heart disease(P<0.05);In the comparison of family history,hypertension,diabetes,coronary heart disease and cancer in the two groups had statistically significant difference(P<0.05).4)Multivariate logistic regression analysis showed that,the risk of obesity in patients with NAFLD increased 4.005 times(OR=4.005,95%CI=2.138-7.499);The risk of obesity in patients with abdominal NAFLD increased 6.396 times(OR=6.396,95%CI=2.394-17.085);The risk of hyperglycemia in patients with NAFLD increased 8.045 times(OR=8.045,95%CI=1.889-34.258);High triglycerides with an increased risk of NAFLD increased 2.770 times(OR=2.770,95%CI=1.329-5.775);Low HDL levels in patients with high risk of developing NAFLD increased 6.908 times(OR=6.908,95%CI=2.000-23.864);High LDL levels in patients with risk of NAFLD increased by 3.344 times(OR=3.344,95%CI=1.228-9.103);Abnormal ALT in patients with NAFLD the risk increased 3.795 times(OR=3.795,95%CI=1.500-9.603).5)The MTHFR rs1801131 gene and NAFLD have no significant difference of distribution(χ2=1.776,P=0.411;χ2=1.520,P=0.218;P>0.05).In the female population,the risk of NAFLD was significantly higher in the individuals with AA genotype of additive genetic model,which was a risk factor for NAFLD(GG,GA vs AA,OR=2.699,95%CI =1.243-5.859,P =0.010);In the recessive inheritance model,the risk of NAFLD was significantly higher in AA genotype carriers(GG + GA vs AA,OR =2.444,95%CI=1.158-5.158,P=0.016);In the allele,the risk of NAFLD was significantly higher in the A allele carriers(G vs A,OR=1.473,95%CI=1.068-2.031,P=0.018)and male populations were not susceptible to genetic models and alleles with NAFLD(P> 0.05).In NAFLD patients,AA genotype FPG was significantly higher than that of GG and GA(AA>GG>GA)genotype;AA genotype AST was significantly higher than that of GG and GA(AA>GA>GG)genotype.In male,GG as carriers of DBP were significantly higher than that of GA and AA(GG>GA>AA)genotype;AA genotype AST was significantly higher than that of GA and GG(AA>GA>GG)genotype;In female,AA genotype BMI,waist circumference and DBP levels were significantly higher GA and GG(AA>GA>GG)genotype;AA genotype FPG was significantly higher than that of GG and GA(AA>GG>GA)genotype,the differences were statistically significant(P<0.05).Other clinical biochemical indexes among different genotype were no statistical significance(P>0.05).6)The MTHFR rs1801131 gene and NAFLD have no significant difference of distribution(χ2=1.187,P=0.552;χ2=0.004,P=0.951;P>0.05).In NAFLD patients,GG genotype TC was significantly higher than that of TT and GT GG>TT>GT)genotype.In male,GG genotype TC was significantly higher than that of TT and GT(GG>TT>GT)genotype.In female,GG genotype LDL-C was significantly higher than that of TT and GT GG>TT>GT)genotype,the differences were statistically significant(P<0.05),other clinical and biochemical indexes in different genotypes showed no significant difference(P>0.05).7)The MTRR rs1801394 gene and NAFLD have no significant difference of distribution(χ2=1.179,P=0.555;χ2=0.911,P=0.340;P>0.05).Conclusion: 1)BMI,WC,WHtR and NAFLD have correlation in Uygur population.Obesity,abdominal obesity,high uric acid,low HDL levels,high LDLlevels and abnormal ALT were risk factors of NAFLD.2)MTHFR rs1801133 gene is associated with the occurrence of nonalcoholic fatty liver in Uygur population in Xinjiang.Particularly in the female population,the risk of developing nonalcoholic fatty liver in individuals with the A allele and the mutant homozygous AA gene was significantly higher.MTHFR gene rs1801133 polymorphism loci affected FPG,AST,DBP,BMI,WC levels.3)The MTHFR gene rs1801131 polymorphism was no correlation with NAFLD in Uygur population.MTHFR gene rs1801133 polymorphism has an effect on TC and LDL-C levels.4)The MTRR rs1801394 gene polymorphism was no correlation with NAFLD in Uygur population.