Association Test Of Serum Folic Acid Level, MTHFR C677T And MTRR A66G Polymorphisms, And Triglycerides Level In Mild-to-moderate Hypertensive Patients

Objective To test the inter-relationships of the serum folic acid level and potential risk factors, including MTHFR C677T and MTRR A66G polymorphisms and triglycerides level in mild-to-moderate hypertensive patients.Methods A total of 480 eligible patients with essential hypertension, aged 28-75, from Haerbin, Shenyang, Beijing, Xi'an, Shanghai and Nanjing were recruited, and randomly devided into three groups separately with different drug combination treatments, 10mg enalapril, 10 mg enalapril+0.4 mg folate, and 10 mg enalapril + 0.8 mg folate, for consecutive 8 weeks , where 10mg enalapril treatment group defined as the control group, and combined with different daily dose of 0.4 mg or 0.8 mg folic acid as the trials. In this present study, major variables containing pre- and post-treatment serum folic acid and triglycerides levels, and MTHFR C677T and MTRR A66G genotypic data were collected, and further analyzed for the inter-relationships of the serum folic acid and its potential risk factors C677T polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and A66G polymorphisms in methionine synthase reductase (MTRR), and triglycerides level by general statistical methods (i.e. t-test, ANOVA, and multivariate regression models).Resultsâ‘ The serum folic acid level of the individuals with homozygous TT genotype of MTHFR C677T genetic variate is significantly lower than that of those with homozygous CC or heterozygous CT(P<0.05). Further test results showed that the serum folic acid level of the MTHFR 677 TT genotype has more significantly different distribution in the south chinese or the first two tertile younger groups of age distribution or the middle tertile group of basic folic acid level; However, no significant difference of the serum folic acid level between the individuals with heterozygous CT and those with homozygous CC was observed.â‘¡MTHFR C677T and MTRR A66G polymorphisms can affect therapeutic response to folic acid. There is a joint effect of MTHFR C677T and MTRR A66G polymorphisms on the changes in serum folic acid level before and after treatment of the trial. The folic acid therapeutic effect in subjects with MTRR 66AA genotype is significantly lower than that of those with MTRR 66 GG or GA genotype; But no significant difference of the therapeutic effect on the changes of serum folic acid level between the individuals with homozygous GA and those with heterozygous GG.. Adjusted for multivariables such as age, BMI, different study centers, the therapeutic effect on the folic acid in subjects with MTHFR 677 TT genotype is significantly lower than that of those with MTHFR 677 CT or CC genotype; But no significant difference of the therapeutic effect on the folic acid between the individuals with homozygous CT and those with heterozygous CC.â‘¢The basic serum folic acid level is in significantly inverse correlation with the basic serum triglyerides level in the male, but not in female. There is no significant difference of the changes of the serum triglyerides level in the trial groups compare with the control group. The folic acid can affect the distribution of triglyerides in the organism; but the different folic acid intakes have a different modulating ability and mode on triglyerides in the male and female.Conclusions The basic serum folic acid level in the individuals with homozygous TT genotype of MTHFR C677T is significantly lower than that of those with CC or CT genotype in the mild-to-moderate hypertensive patients. But there is more significant association of the basic serum folic acid level and MTHFR C677T genetype in the different conditional subgroups. MTHFR C677T and MTRR A66G polymorphisms can moderately modify therapeutic effect of the folic acid, and a joint effect on the changes in serum folic acid level between C677T and A66G polymorphisms is detected. The serum folic acid level is tightly associated with triglyerides in the mild-moderate hypertensive patients. The folic acid level can also affect the distribution of triglyerides in the patients, but there is different association of the basic serum folic acid level and triglycerides and that of changes of the serum triglycerides level among the different treatments in the male and female.