Association Of The Polymorphism Of MTRR Gene With The Efficacy Of Folic Acid Therapy In The Treatment Of Hyperhomocysteinemia

Hyperhomocysteinaemia(HHcy) is an independent risk factor for cardiovascular disease, and is also a risk factor of birth defects, peripheral vascular disease, nervous system degenerative disease, chronic kidney disease and other diseases. Oral folic acid can reduce plasma Hcy concentration, and it is recommended for the treatment of HHcy therapy. But with adequate dose and time of folic acid intervention, the Hcy concentration of patients are still higher than the normal value, so we need to explore this phenomenon from the perspective of genetics. Methionine synthase reductase(MTRR) transfers methyl from methylation Vitamin B12 to Hcy, contributes to complete the Hcy methylation metabolic process, catalyzes the regeneration of Vitamin B12 activity, maintains the activated state of MTR, plays an important role in the metabolism of methionine and folic acid, and is an important determinant of the concentration of plasma Hcy. In view of the above ideas, this study aims to explore the relationship between MTRR gene polymorphisms and the efficacy of folic acid treatment.ObjectiveExplore the relationship between MTRR gene polymorphisms and the efficacy of folic acid therapy in the treatment of hyperhomocysteinemia, and the role of gene-environment interaction in the treatment efficacy.MethodWe chose the patients who examined the plasma Hcy level between July and September 2014 in the fifth affiliated hospital of Zhengzhou University. Those patients(Hcy≥15μmol/L) entered into queue and were treated with folic acid(5mg/d) for an intervention. After observation period of three months, telephone was used to follow up their plasma Hcy levels. According to the review results, a total of 186 cases(Hcy≥15μmol/L) were divided into the failure group, and a total of 198 cases(Hcy<15μmol/L) were divided into the success group. The data was collected by the questionnaire survey. The genotypes of three SNPs of MTRR gene(rs1801394, rs162036, rs10380) were detected by time of flight mass spectrometry biochip systemtime.Database was established through parallel double entry by EpaData3.1. SAS9.1 statistical software was used for data processing and statistical analysis. Independent t test and chi-square test were performed to compare the distribution differences of features of the cases and controls. Unconditioned logistic regression was conducted to assess odds ratios(OR) and 95% confidence interval(95%CI) adjusting for the covariate values. Hardy Weinberg equilibrium was analyzed using IHG on-line software(http://ihg.gsf.de/cgi-bin/hw/hwa1.pl). Haplotype frequencies were estimated using SHEsis(http://analysis.bio-x.cn/my Analysis.php). Gene-environment interaction was evaluated using multifactor dimensionality reduction(MDR) software.Resultrs1801394 AG genotype(OR=3.34, 95%CI: 2.05-5.45),(AG+GG) genotype(OR=3.03, 95%CI:1.90-4.84) and G allele(OR=2.35, 95%CI:1.67-3.31) could increase the risk of the failure of folic acid therapy in the treatment of hyperhomocysteinemia. rs162036 AG genotype(OR=0.32, 95%CI:0.19-0.55),(AG+GG) genotype(OR=0.33, 95%CI:0.20-0.55) and G allele(OR=0.42, 95%CI: 0.28-0.62) could reduce the risk of the failure of folic acid treatment. There was no association between rs10380 and the efficacy of folic acid therapy. Haplotype GA(rs1801394-rs162036) can increase the risk of the failure of folic acid treatment(OR=2.18, 95%CI:1.54-3.09). Haplotype AG(OR=0.34, 95%CI:0.22-0.51) can reduce the risk of the failure of folic acid treatment. The result of gene-environment interaction demonstrated that there was a significantly interaction between rs1801394 and coronary heart disease(OR=4.57, 95%CI:2.97-7.03), it could increase the risk of the failure of folic acid treatment.ConclusionMTRR gene rs1801394 loci and rs162036 loci are associated with the risk of the failure of folic acid therapy in the treatment of hyperhomocysteinemia. The SNP haplotype with MTRR gene is associated with the risk of the failure of folic acid therapy in the treatment of hyperhomocysteinemia. There are significantly interaction between rs1801394 and coronary heart disease in the efficacy of folic acid treatment.