Environmental and Genetic Determinants of Hyperhomocysteinemia in Chinese Hypertensives

Background:Hyperhomocysteinemia (HHcy) is a well established and independent risk factor for stroke and cardiovascular disease (CVD). Furthermore, an increased homocysteine (Hcy) level showed a more than multiplicative effect on risk in hypertensive subjects (H-type hypertension) with a relative risk of10-folds for stroke..Objective:To obtain the prevalence of HHcy in rural Chinese hypertensive subjects and to identify the major determiants of HHcy..Methods:We conducted a community-based cross-sectional study in two rural regions of Northern (Lianyungang) and Southern (Anqing) China from2008to2009. The Hcy levels were measured by enzyme immunoassay methods and the methylenetetrahydrofolate reductase (MTHFR)677C/T polymorphism was determined by high-throughput TaqMan allelic discrimination assay. Blood pressure (BP), body mass index (BMI) and other related demographic and lifestyle information were obtained through a standard questionnaire. Multivariate logistic regression model was performed to evaluate the associations of HHcy with the potential risk factors.Results:A total of21,373hypertensive patients with the age range of45to75were available for the data analysis. Overall, the prevalence of HHcy (defined as Hcy≥10.0umol/L) was65.3%in males and43.0%in women in Chinese rural hypertensive patients. Gender, age, alcohol consumption, and MTHFR677C/T were associated with HHcy risk. On the logistic regression analysis, multivariate modeling further identified that among men, the odds ratios of HHcy were significantly increased from1.28to3.01with age groups from50-55to70-75yrs of age, compared with the youngest reference group (45-50yrs of age). Similarly the graded increase in odds ratios of HHcy from1.45to5.74were observed with increased age groups among women. Women in Anqing had a significantly increased prevalence of HHcy than in Lianyungang (OR=0.85;95%CI:0.68-1.07),but not men. The subjects with CT and TT genotype had significantly higher risks of HHcy both in men1.32(95%CI:1.19-1.47) and3.92(95%CI:3.39-4.52) Alcohol consumption is significantly associated was20%reduction in risk of HHcy compared with non-drinkers. Cigarette smoking is not significantly associated with HHcy in this population.Conclusions:our study found that there was a high prevalence of HHcy in rural Chinese hypertensive patients and that the gender, age, and MTHFR677C/T were the major determinants of HHcy. Objective:To evaluate the association of methylenetetrahydrofolate reductase (MTHFR) gene677C/T polymorphism with hyperhomocysteinemia (HHcy) in Chinese hypertensive patients.Methods:We measured plasma tHcy level and677C/T genotype in1058Chinese hypertensive patients from four previous studies. We used10,15,20μmol/L as cut-off values for the definition of mild, modest, and severe HHcy, respectively, to evaluate the association of HHcy with MTHFR677C/T polymorphism and calculate the sensitivity and specificity. Logistic modelswere use to estimate the odds ratios of HHcy with MTHFR677C/T genotypes adjusting for potential confounders. The receiver operating characteristics of the models were evaluated with and without inclusion of age and gender.Results:MTHFR677TT genotype is significantly and consistently associated with a higher Homocysteine across the four studies, with an increase in size ranging from38%to68%in the four studies and51%overall. The677C/T polymorphism independently explained about14%of the total variance of the normalized Hcy. The adjusted Odds Ratios for the TT genotype were3.9(95%CI:2.4-6.4),6.5(95%CI:4.0-10.6), and17.9(95%CI:8.4-38.1) for mild, modest, and severe HHcy, respectively. The predicting performance increased with HHcy severity, with sensitivity improved from31.0%for mild HHcy to70.3%for severe HHcy, and with specificity slightly decreased from85.4%to80.3%. Inclusion of gender and age as predictors significantly improves the sensitivity, especially for predicting mild HHcy. Conclusion:With an excellent specificity and moderate sensitivity, the MTHFR677C/T polymorphism could be a useful screening marker for severe HHcy in hypertensive patients.