Effects of MTHFR and MS gene polymorphisms on baseline blood pressure and Benazepril effectiveness in Chinese hypertensive patients.

The development of essential hypertension (EH) and inter-individual differences in response to antihypertensive treatment may partly result from genetic heterogeneity. In this study, we conducted an investigation of the combined effects of 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase (MS) A2756G polymorphisms on baseline blood pressure (BP) and BP response to antihypertensive Benazepril treatment in 823 Chinese hypertensive patients with a fixed daily dosage of 10 mg for 15 consecutive days. When MTHFR C677T and MS A2756G polymorphisms were modelled together with adjustment for important covariates, only MTHFR C677T was associated with baseline systolic BP (SBP) (ß (s.e.)=2.84 (1.10), P=0.0096) or baseline diastolic BP (DBP) (ß (s.e.)=2.19 (0.65), P=0.0008). Modelled together with adjustment for important covariates, MTHFR C677T and MS A2756G polymorphisms were both independently associated with increased DBP response (baseline minus post-treatment) to Benazepril treatment (C677T: ß (s.e.)=1.58 (0.76), P=0.038; A2756G: ß (s.e.)=2.14 (0.89), P=0.016). Neither polymorphism was associated with SBP response to Benazepril treatment. There were no significant interactions or effect modification between MTHFR C677T and MS A2756G gene polymorphisms in models of baseline SBP, baseline DBP or DBP response to Benazepril treatment. Our results suggest that the effects of MTHFR C677T and MS A2756G gene polymorphisms may have pivotal roles in the aetiology of EH and BP response to Benazepril treatment.

Effects of protein coding polymorphisms in the kallikrein 1 gene on baseline blood pressure and antihypertensive response to irbesartan in Chinese hypertensive patients.

The aim of this study was to determine the association between coding variants in the human tissue kallikrein 1 (KLK1) gene and baseline blood pressure (BP) and antihypertensive response to irbesartan treatment in Chinese hypertensive patients. A total of 1061 hypertensives were recruited and received daily oral dosage of 150 mg irbesartan for 4 weeks. Predose BPs, BPs and blood irbesartan concentrations at postdose on the 28th day were all measured. Common functional single-nucleotide polymorphisms (SNPs) in the KLK1 gene were genotyped. On the basis of the HapMap data of Han Chinese in the Beijing population, two non-synonymous polymorphisms with minor allele frequency>0.1, SNP rs5517 (Glu162Lys) and rs5516 (Gln121Glu), were selected. Those with GG genotype in the rs5516 locus had higher average baseline systolic BP (SBP) than CC subjects (ß±s.e.: 5.0±2.3, P=0.033); and no associations of rs5517 with baseline BP (diastolic BP (DBP) and SBP) and BP responses, or rs5516 with baseline DBP and BP response were observed. In a haplotype-based association test for the KLK1 gene, the Haplo-special score analyses identified that haplotype AG was marginally associated with SBP response (specific score: 1.75 for P=0.08), but not with DBP response. We did not find any associations between haplotypes (GC and AC) and BP responses. The Haplo-GLM analyses showed that, compared with haplotype GC subjects, the subjects with haplotype AG had a marginally greater SBP response (adjusted ß±s.e.: 1.81±0.97, P=0.06), but DBP response did not differ. This study suggests that rs5516 in the KLK1 gene may be involved in the development of essential hypertension and in the regulation of SBP-lowering response to irbesartan in Chinese hypertensives.

Menstrual cycle lengths and bone mineral density: a cross-sectional, population-based study in rural Chinese women ages 30-49 years.

INTRODUCTION: The menstrual cycle involves periodic fluctuations in estrogen and progesterone levels. Longer cycles have been associated with longer follicular phase, delayed estrogen peak and a lower mean oestradiol level of the entire cycle. METHODS: We hypothesized that prolonged menstrual cycle length is associated with decreased bone mineral density (BMD) in a population of pre- and perimenopausal women. This population-based cross-sectional study was conducted in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD measurements were taken at four skeletal sites: whole body, total hip, femoral neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the prior year were assessed by questionnaire. RESULTS: Prolonged menstrual cycle was consistently associated with decreased BMD at whole body, total hip, and femoral neck in both age 30-39, and age 40-49 stratum (p(trend)<0.05). Prolonged menstrual cycle was also associated with decreased lumbar spine BMD for women aged 40-49 (p(trend)<0.05). Among women with normal cycles aged 30-39, menstrual cycle length in the previous year was inversely associated with whole-body BMD (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and femoral neck BMD relative to women with short normal cycles in the 30-39 age group; and had significantly lower whole body and total hip BMD relative to short normal cycles in the 40-49 age group. BMD in polymenorrheic women did not differ from BMD in women with short normal cycles at any of the skeletal sites. CONCLUSIONS: We conclude that prolonged menstrual cycle length is associated with decreased BMD in pre- and perimenopausal women in this population.

Serum DDT, age at menarche, and abnormal menstrual cycle length.

BACKGROUND: Although dichlorodiphenyl trichloroethane (DDT) exposure is known to affect human endocrine function, few previous studies have investigated the effects of DDT exposure on age at menarche or menstrual cycle length. METHODS: A cross sectional study was conducted to study the effects of DDT exposure on age at menarche and menstrual cycle length among 466 newly married, nulliparous female Chinese textile workers aged 20-34 years enrolled between 1996 and 1998. Serum was analysed for DDT and its major metabolites. Multivariate linear regression was used to estimate DDT exposure effects on age at menarche and multivariate logistic regression was used to estimate DDT exposure effects on odds of experiencing short or long cycles. RESULTS: Relative to those in the lowest DDT quartile, the adjusted mean age at menarche was younger in those in the fourth quartile (-1.11 years). Modeled as a continuous variable, a 10 ng/g increase in serum DDT concentration was associated with an adjusted reduction in age at menarche of 0.20 years. Relative to those in the lowest DDT quartile, odds of any short cycle (<21 days) in the previous year were higher for those in the fourth quartile (odds ratio = 2.78; 95% CI 1.07 to 7.14). There were no associations between serum DDT concentrations and odds of experiencing a long cycle (>40 days). CONCLUSION: Results suggest that DDT exposure was associated with earlier age at menarche and increased risk of experiencing a shortened menstrual cycle.

Exposure-response relationship between paternal smoking and children's pulmonary function.

We conducted a cross-sectional study to investigate paternal smoking and children's pulmonary function in rural communities of Anqing, China. Our analysis included 1,718 children 8 to 15 yr of age whose mothers were never-smokers. Multiple linear regression models were used to estimate the effect of paternal smoking on children's pulmonary function, with adjustment for children's age, sex, weight, height, square of height, asthma, and father's education. When compared with children of never-smoking fathers, children of smoking fathers had small, but detectable deficits in FEV(1) (-36 ml, SE = 20) and FVC (-37 ml, SE = 22). When children of smoking fathers were subdivided into two subgroups, father smoked < 30 cigarettes/day and >/= 30 cigarettes/day, we found that children whose fathers smoked >/= 30 cigarettes/day had the largest deficits in both FEV(1) (-79 ml, SE = 30) and FVC (-71 ml, SE = 34). This monotonic exposure-response relationship remained in all strata when we further stratified our analysis by children's sex and asthma status. Our data also suggested that the relationship was greatest among nonasthmatic girls, although neither sex nor asthma interaction terms were statistically significant. We conclude that there is a monotonic exposure-response relationship between paternal smoking and decline of pulmonary function in children in this rural Chinese population.

Indoor air pollution and respiratory health in urban and rural China.

During the summer of 1999, information about respiratory health outcomes and relevant covariates was collected from 3,709 Chinese adults in Beijing, Anqing City, and rural communities in Anqing Prefecture. Indoor PM10 and SO2 were measured in a random sample of selected households. Using logistic regression and controlling for important covariates (excluding PM10 and SO2) and familial intraclass correlation, highly significant differences were found between study areas in the prevalences of chronic cough, chronic phlegm, wheeze, and shortness of breath, but not physician-diagnosed asthma. Generally, the lowest prevalence of respiratory symptoms was observed in Anqing City, a higher prevalence in rural Anqing, and the highest prevalence in Beijing. Median indoor concentrations of PM10 were similar in Anqing City (239 microg/m3) and rural Anqing (248 microg/m3), but much higher in Beijing (557 microg/m3). Median indoor concentrations of SO2 were similar in all three areas (Beijing: 14 microg/m3, Anqing City: 25 microg/m3, rural Anqing: 20 microg/m3).