| Objective:To investigate distributed characteristic of the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the methionine synthase (MS) A2756G polymorphism and their united genotypes of MTHFR A1298C and MS A2756G in Xinjiang Kazakhs people. And to research the effects of MTHFR A1298C and MS A2756G genetic mutation and united two genotypes on plasma homocysteine level in Xinjiang Kazakhs with essential hypertension (EH). Methods: More than 400 Xinjiang Kazakhs aged more than 30 years old were recruited in this population-based case-control study by cluster sampling who lived in pasture area of Tacheng, Yili, Aretai region in Xinjiang. After questionnaire and physical examination, they were divided into hypertensives group (EH) whose systolic blood pressure (SBP)≥140mmHg and/or diastolic blood pressure (DBP)≥90mmHg and normotensives group (NT) whose blood pressure<140/90mmHg according to the guideline of the hypertensive prevention and treatment of China in 2005. We extracted the genome DNA of peripheral leucocyte by kits or phenol-chloroform, and measured their gene polymorphisms of MTHFR A1298C and MS A2756G by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) method. The level of plasma homocysteine were measured using enzymoimmunoassay. We studied the relationship of the polymorphisms and the united genotypes with EH and plasma homocysteine level and researched the association of the genetypes with EH by SPSS15.0 statistic software. Results: 1) There were three kinds of genotypes and two kinds of alleles of MTHFR gene A1298C polymorphism be detected in Xinjiang Kazakhs. In this population, the frequencies of the genotypes AA, AC, CC were 64.72%, 30.84%, 4.44% and the frequencies of alleles A, C were 80.14%, 19.86%, respectively. The x 2 test for the Hardy-Weinberg equilibrium with polymorphism was not statistically significant ( x 2=0.414, P=0.813). The distributed genotypic frequencies of AA, AC, CC were 67.98%, 28.08%, 3.94% in EH group and 61.78%, 33.33%, 4.89% in NT group, respectively. The distributed allelic frequencies of A, C were 82.02%, 17.98% in EH group and 78.44%, 21.56% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between EH group and NH group ( x 2=1.806, P=0.405 and x 2=1.714, P=0.190). Through to analyze the data stratified with gender (male and female), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P>0.05). There was significant difference in levels of plasma homocysteine between EH group and NT geoup, (14.87±8.76 vs 11.15±5.21, P<0.01). Either EH group or NT group, the level of plasma homocysteine in male was higher than that of female, There was significant difference between male and female (17.26±9.07μmol/L vs 12.65±5.04μmol/L, P<0.01, and 12.75±6.13 vs 9.82±5.09, respectively, P<0.05). Either in male or in female, the level of plasma homocysteine in EH group was higher than that of NT group (17.26±9.07μmol/L vs 12.75±6.13μmol/L, P<0.01, and 12.65±5.04μmol/L vs 9.82±5.09μmol/L, respectively, P<0.05). There was no significant difference in the level of plasma homocysteine among subjects with the AA, AC and CC genotypes (13.19±8.90μmol/L, 12.24±4.77μmol/L and 11.99±5.40μmol/L, P>0.05). There was no significant difference in age, BMI, SBP, DBP, FBG, BUN, Cr, UA, TC, TG, HDL, LDL, Apo-a among subjects with the AA, AC and CC genotypes (P>0.05). Age and BMI were independent risk factors for essential hypertension in Xinjiang Kazakhs. The genotypes of the MTHFR A1298C polymorphism and the level of plasma homocysteine were excluded as independent variables which related to the blood pressure of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 2) There were three kinds of genotypes and two kinds of alleles of MS gene A2756G polymorphism be detected in Xinjiang Kazakhs. In this population, the frequencies of the genotypes AA, AG, GG were 78.15%, 20.19%, 1.66% and the frequencies of alleles A, G were 88.24%, 11.76%, respectively. The x 2 test for the Hardy-Weinberg equilibrium with polymor- phism was not statistically significant ( x 2=0.3072, P=0.8576). The distributed genotypic frequencies of AA, AG, GG were 76.12%, 21.39%, 2.49% in EH group and 80.00%, 19.09%, 0.91% in NT group, respectively. The distributed allelic frequencies of A, G were 86.82%, 13.18% in EH group and 89.55%, 10.45% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between EH group and NH group ( x 2=0.926, P=0.336 and x 2=1.508, P=0.219). Through to analyze the data stratified with gender (male and female) , the distribution of genotypic and allelic frequencies had no significant difference between two groups (P>0.05). There was no significant difference in the level of plasma homocysteine among subjects with the AA, AG and GG genotypes (12.74±7.88μmol/L, 12.95±5.04μmol/L and 13.38±5.84μmol/L, respectively, P>0.05). There was no significant difference in age, BMI, SBP, DBP, FBG, BUN, Cr, UA, TC, TG, HDL, LDL, Apo-a among subjects with the AA, AG and GG genotypes (P > 0.05). Age and BMI were independent risk factors for essential hypertension in Xinjiang Kazakhs. The genotypes of the MS A2756G polymorphism and the level of plasma homocysteine were excluded as independent variables which related to the blood pressure of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 3) There were eight kinds united genotype between MTHFR A1298C and MS A2756G: AA/AA, AA/AG, AA/GG, AC/AA, AC/AG, CC/AA, CC/AG, CC/GG, but there was no AC/GG united genotype be detected. There was no significant difference in united genotypes distribution between EH group and NT group (P>0.05). We used an unconditional logistic regression model to analyze the relation between the united genotypes and essential hypertension. When the MTHFR 1298CC/MS 2756AA was defined as the reference, the MTHFR 1298AA/MS 2756GG showed a higher adjusted OR (1.80) , and MTHFR 1298CC/MS 2756AG showed a lower adjusted OR (0.240), but statistical significance were not be found for each combination of alleles (P>0.05). Comparing the level of plasma homocysteine among each combination of alleles, the level of plasma homocysteine in MTHFR 1298AA/MS 2756GG was highest (13.30±3.56μmol/L); the level of plasma homocysteine in MTHFR 1298CC/MS 2756AA was lowest (12.08±4.88μmol/L); but there was no significant difference between the each combination group. Conclusions : 1) There existed A1298C polymorphisms of MTHFR gene and A2756G of MS gene in Xinjiang Kazakhs people. There were three kinds of genotypes AA, AC, CC and two kinds of alleles A, C in A1298C, polymorphisms of MTHFR gene, respectively. There were three kinds of genotypes AA, AG, GG and two kinds of alleles A, G in A2756G polymorphism of MS gene. The genotypic frequencies were in Hardy-Weinberg equilibrium. 2) There was probably no relation between MTHFR A1298C genetic polymorphism and essential hypertension in Xinjiang Kazakhs. The MTHFR A1298C genetic polymorphism probably was not important hereditary factor at affecting the level of plasma homocysteine in Xinjiang Kazakhs. 3) There was probably no relation between MS A2756G genetic polymorphism and essential hypertension in Xinjiang Kazakhs. The MS A2756G genetic polymorphism probably was not important hereditary factor at affecting the level of plasma homocysteine in Xinjiang Kazakhs. 4) The level of plasma homocysteine were significantly higher in EH group than NT group in Xinjiang Kazakhs, and there was significant difference in gender, the level of plasma homocysteine in male was higher than that in female. Higher level of homocysteine was probably an risk factor for hypertension in Xinjiang Kazakhs, but it was not an independent risk factor for hypertension in Xinjiang Kazakhs. 5) There was probably no relation between the combination of MTHFR A1298C and MS A2756G genetic polymorphism and essential hypertension in Xinjiang Kazakhs. The combinations of MTHFR A1298C and MS A2756G genetic polymorphism probably were not important hereditary factors at affecting the level of plasma homocysteine in Xinjiang Kazakhs.
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