BackgroundMethylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms are important genetic determinants for homocysteine (Hcy) levels, and are associated with several disorders. These polymorphisms are heterogeneously distributed worldwide. Our objective was to explore the geographical distributions of these polymorphisms in China.Methodologies15357 healthy adults were recruited from 10 regions. Buccal samples were collected and genomic DNA was isolated. Genotyping was performed using the fluorogenic 5′-nuclease assay.Principal FindingsThe prevalence of the three polymorphisms among different populations from China varied significantly and showed apparent geographical gradients. For MTHFR C677T, the frequencies of the 677T allele and the 677TT genotype were significantly higher among northern populations and ranged from the lowest values (24.0% and 6.4%, respectively) in Hainan (southern) to the highest values (63.1% and 40.8%, respectively) in Shandong (northern). For MTHFR A1298C, the 1298C allele and the 1298CC genotype frequencies were significantly higher among southern populations and increased from low values (13.1% and 1.4%, respectively) in Shandong to high values (25.7% and 6.7%, respectively) in Hainan. For A66G, the 66G allele and the 66GG genotype frequencies increased from lower values (23.7% and 5.4%, respectively) in Shandong to higher values (29.2% and 8.6%, respectively) in Hainan. The overall frequency of the 677T allele, 677TT genotype, 1298C allele, 1298CC genotype, 66G allele and 66GG genotype in the Chinese Han population was 45.2%, 23.2%, 18.6%, 3.9%, 25.7%, and 6.6%, respectively. No gender differences were found in the prevalence of both the MTHFR C677T and MTRR A66G polymorphisms.ConclusionsThis study indicates that there are marked geographical variations in the prevalence of the three polymorphisms among Chinese Han populations. Our baseline data may be useful for future researches in related fields.
Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 μmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3–97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.
BackgroundSeveral epidemiological studies have investigated the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with hypertension (H) or hypertension in pregnancy (HIP). However, the results were controversial. We therefore performed a comprehensive meta-analysis to provide empirical evidences on the associations.MethodologiesThe English and Chinese databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed in our study.Principal FindingsA total of 114 studies with 15411 cases and 21970 controls were included, 111 studies with 15094 cases and 21633 controls for the C677T polymorphism and 21 with 2533 cases and 2976 controls for the A1298C polymorphism. Overall, the C677T polymorphism was significantly associated with H and HIP (H & HIP: OR = 1.26, 95% CI = 1.17–1.34; H: OR = 1.36, 95% CI = 1.20–1.53; HIP: OR = 1.21, 95% CI = 1.08–1.32). Stratified analysis by ethnicity revealed a significant association among East Asians and Caucasians, but not among Latinos, Black Africans, and Indians and Sri Lankans. In the stratified analyses according to source of controls, genotyping method, sample size and study quality, significant associations were observed in all the subgroups, with the exception of population based subgroup in H studies and large sample size and “others” genotyping method subgroups in HIP studies. For the A1298C polymorphism, no significant association was observed either in overall or subgroup analysis under all genetic models.ConclusionsThis meta-analysis suggests that the MTHFR C677T rather than A1298C polymorphism may be associated with H & HIP, especially among East Asians and Caucasians.
Although several studies have investigated the associations of neck circumference (NC) with arterial blood pressures (BPs) and hypertension, no such studies have been conducted among Northern Chinese population. Between April and June 2015, a total of 2631 subjects aged ≥35 years old were recruited from Northeastern China. NC and arterial BPs were measured by trained personnel. Generalized linear and logistic regression analyses were applied to examine the associations of NC with arterial BPs and hypertension risk. The optimal cut-off points of NC for predicting hypertension were assessed by the receiver operating characteristic analysis. We found that NC was significantly associated with arterial BPs and hypertension risk in the Northeastern Chinese adults, even after adjusting for many covariates including body mass index, waist circumference or waist-to-hip ratio. The optimal cut-off values for NC to predict hypertension differed with sex, age, and body mass index. Our study suggests that NC may play an independent role in predicting hypertension beyond the classical anthropometric indices, and that it could be used as a valuable anthropometric measurement for routine assessment in primary care clinics and future epidemiological studies.
BackgroundMethylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, had significant effects on the homocysteine levels. The common functional MTHFR C677T polymorphism had been extensively researched. Several studies had evaluated the relationship between MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM), but the results were still controversial in the Chinese Han population. This meta-analysis was conducted to evaluate the relationship between MTHFR C677T polymorphism and T2DM in the Chinese Han population.MethodsWe searched the relevant studies in multiple electronic databases, which published up to December 2013. We reviewed and extracted data from all the included studies on the relationship between MTHFR C677T polymorphism and T2DM in the Chinese Han population. The odds ratios (ORs) and their 95% confidence intervals (95%CIs) were used to evaluate the relationship. Fixed-effects and random-effects meta-analysis were used to pool ORs by the heterogeneity. Publication bias and sensitivity analysis were also examined.Results29 studies were finally included in our meta-analysis, which contained 4656 individuals with T2DM and 2127 healthy controls. There was a significant relationship between MTHFR C677T polymorphism and T2DM under dominant (OR: 1.70, 95% CI: 1.42–2.02), recessive (OR: 1.48, 95% CI: 1.21–1.80), homozygous (OR: 1.89, 95% CI: 1.47–2.42), heterozygous (OR: 1.58, 95% CI: 1.33–1.87), and additive (OR: 1.46, 95% CI: 1.28–1.68) genetic model in a random-effects model. Subgroup analysis also reached similar results. Sensitivity analysis indicated that the overall result were dependable.ConclusionsThere was a significant relationship between MTHFR C677T polymorphism and T2DM in the Chinese Han population. The results of our meta-analysis suggested that MTHFR 677T allele might be a risk genetic factor of T2DM in the Chinese Han population.
This study aimed to investigate whether conventional predisposing factors modify the associations of homocysteine with blood pressure levels and hypertension. A total of 2615 adults were recruited from Liaoning province. An elevated homocysteine level was significantly associated with increased hypertension risk and blood pressure (all P<.05). Interaction analyses showed that homocysteine acted synergistically with age, overweight/obesity, dyslipidemia, and family history of hypertension to affect hypertension risk, and the relative excess risk due to interaction was 1.21 (95% confidence interval, 0.07–2.35), 0.72 (95% confidence interval, 0.07–1.36), 0.45 (95% confidence interval, 0.06–0.85), and 1.87 (95% confidence interval, 0.77–2.97), respectively. Increases in blood pressure were higher in patients who were overweight/obese or had a family history of hypertension than in their counterparts (all Pinteraction <.05). This study provides some strong evidence for interactions of homocysteine with conventional predisposing factors on hypertension.
Prior evidence indicates that homocysteine plays a role in the development of metabolic syndrome (MetS). Methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms are common genetic determinants of homocysteine levels. To investigate the associations of the MTHFR C677T and MTRR A66G polymorphisms with MetS, 692 Chinese Han subjects with MetS and 878 controls were recruited. The component traits of MetS and the MTHFR C677T and MTRR A66G genotypes were determined. A significant association was observed between the MTHFR 677T allele and increased risk of MetS, high fasting blood glucose, high waist circumference, and increasing number of MetS components. The MTRR A66G polymorphism was associated with an increased risk of MetS when combined with the MTHFR 677TT genotype, although there was no association found between MetS and MTRR A66G alone. Furthermore, the MTRR 66GG genotype was associated with high fasting blood glucose and triglycerides. Our data suggest that the MTHFR 677T allele may contribute to an increased risk of MetS in the northern Chinese Han population. The MTRR A66G polymorphism is not associated with MetS. However, it may exacerbate the effect of the MTHFR C677T variant alone. Further large prospective population-based studies are required to confirm our findings.
Numerous studies have investigated the distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and their associations with diseases in China. In this study we conducted a systematic review and meta-analysis of these studies (715 eligible studies in total).Results revealed that the frequencies of the MTHFR C677T and A1298C polymorphisms varied markedly in different areas and ethnicities, and even showed geographical gradients. The MTHFR C677T polymorphism was significantly associated with 42 clinical disorders (p < 0.05), mostly relating to the diseases of circulatory system, birth defects and cancers. The association of the A1298C polymorphism with three diseases (coronary heart disease, breast cancer and neural tube defects fathers) was statistically significant (p < 0.05). However, according to the Venice criteria, only the associations of the C677T polymorphism with breast and ovarian cancers were assessed as having strong epidemiological credibility. This is the first study to provide a comprehensive assessment of the current status and gaps in genetic epidemiological study of the two polymorphisms in China, and its findings may be useful for medical and public health practices. Future studies are warranted to focus on the interactions of MTHFR genes with environmental exposure and with other genes, and to improve their methodological quality and reporting of findings.
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