Interactions of arsenic metabolism with arsenic exposure and individual factors on diabetes occurrence: Baseline findings from Arsenic and Non-Communicable disease cohort (AsNCD) in China.

The interaction between arsenic metabolism and potential modifiers on the risk of diabetes is unclear. This research aimed to investigate arsenic metabolism and diabetes prevalence and to identify the interactive effects of arsenic metabolism with some risk factors on diabetes in a Chinese population. A baseline cross-sectional survey was performed in two areas with groundwater arsenic contamination in China. Arsenic levels in water and arsenic metabolites in urine were analyzed. The proportions of each arsenic metabolite (inorganic arsenic [iAs%], monomethylarsonic acid [MMA%], and dimethylarsinic acid [DMA%]) were computed to evaluate arsenic metabolism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between arsenic and diabetes. Interaction on the additive scale between arsenic methylation index and effect modifier was evaluated by calculating the relative excess risk due to interaction (RERI). Compared with participants in the lower tertile of MMA%, participants in the middle and upper tertiles of MMA% were less prone to diabetes (OR: 0.47 and 0.31, respectively). However, participants in the upper tertiles of urinary DMA% (OR: 3.18) were more likely to have diabetes than those participants in the lower tertiles. The stratified analyses revealed that a one-unit increase in DMA% was associated with higher odds of diabetes in females (OR: 1.06, 95% CI: 1.01, 1.11), older people (OR: 1.05, 95% CI: 1.00, 1.10), and subjects with body mass index (BMI) under 25 kg/m2 (OR: 1.07, 95% CI: 1.01, 1.14). The additive interactions between DMA% and female gender (RERI: 0.40, 95% CI: 0.01, 11.88), DMA% and age (RERI: 0.02, 95% CI: 0.01, 8.85), as well as DMA% and BMI (RERI: 0.49, 95% CI: 0.01, 9.62), were statistically significant. In conclusion, efficient arsenic metabolism is associated with higher odds of diabetes. Urinary DMA% and individual factors interact to synergistically influence diabetes occurrence in the Chinese population.

Gender Stratified Analyses of the Association of Skinfold Thickness with Hypertension: A Cross-Sectional Study in General Northeastern Chinese Residents.

The association of hypertension with skinfold thickness (ST) in adults is not clear. Our study was aimed at finding out the association of hypertension with ST in different gender and obesity categories. This is a cross-sectional study based on 2336 Chinese residents (767 men). Both subscapular skinfold thickness (SST) and tricep skinfold thickness (TST) were examined. We estimated the association of hypertension with per SD increase of SST and TST using multivariable logistic regression analyses in men and women. Six subgroups were stratified using cutoff points of body mass index (BMI) and ST: larger and smaller ST in normal weight (BMI < 24 kg/m²), overweight (24 kg/m² ≤ BMI < 28 kg/m²) and obesity (BMI ≥ 28 kg/m²), respectively. The association of hypertension with ST was only shown in women after adjustment for other risk factors. Among women of the normal weight subgroup, higher prevalence of hypertension was shown in those with larger ST. No difference of the prevalence of hypertension was found between women with larger ST in the normal weight subgroup and those with smaller ST in overweight or obesity subgroups. Our study suggested that even for people with normal weight, it was necessary to monitor the subcutaneous fat using ST for preventing hypertension at least in general Chinese women.

Interactions of homocysteine and conventional predisposing factors on hypertension in Chinese adults.

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.

Neck circumference associated with arterial blood pressures and hypertension: A cross-sectional community-based study in northern Han Chinese.

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.

Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes.

Although both methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms have been associated with type 2 diabetes (T2D), their interactions with being overweight/obesity on T2D risk remain unclear. To evaluate the associations of the two polymorphisms with T2D and their interactions with being overweight/obesity on T2D risk, a case-control study of 180 T2D patients and 350 healthy controls was conducted in northern China. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). After adjustments for age and gender, borderline significant associations of the MTHFR C677T and MTRR A66G polymorphisms with T2D were observed under recessive (OR = 1.43, 95% CI: 0.98-2.10) and dominant (OR = 1.43, 95% CI: 1.00-2.06) models, respectively. There was a significant interaction between the MTHFR 677TT genotype and being overweight/obesity on T2D risk (AP = 0.404, 95% CI: 0.047-0.761), in addition to the MTRR 66AG/GG genotypes (RERI = 1.703, 95% CI: 0.401-3.004; AP = 0.528, 95% CI: 0.223-0.834). Our findings suggest that individuals with the MTHFR 677TT or MTRR 66AG/GG genotypes are more susceptible to the detrimental effect of being overweight/obesity on T2D. Further large-scale studies are still needed to confirm our findings.

Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms: A cross-sectional descriptive study of 13,473 Chinese adult women.

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited.We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms.In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D' and r values were 0.883 and 0.143, respectively.In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs.

Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population.

BACKGROUND: Little is known regarding the interactions of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with overweight/obesity on serum lipid profiles. The aim of the current study was to explore interactions between the two polymorphisms and overweight/obesity on four common lipid levels in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. METHODS: A total of 2239 participants (750 females and 1489 males) were enrolled into this study. The genotypes of the MTHFR C677T and MTRR A66G were determined by a TaqMan assay. Overweight and obesity were defined as a body mass index between 24 and 27.99 and ≥ 28 kg/m2, respectively. The interactions were examined by factorial design covariance analysis, and further multiple comparisons were conducted by Bonferroni correction. RESULTS: There was no significant difference in the genotypic and allelic frequencies between females and males (MTHFR 677 T allele: 54.47 % for females and 54.40 % for males; MTRR 66G allele: 24.73 % for females and 24.71 % for males). Interaction between the MTHFR C677T polymorphism and overweight/obesity on serum triglyceride levels, and interaction between the MTRR A66G polymorphism and overweight/obesity on serum high-density lipoprotein cholesterol levels were detected in women (P = 0.015 and P = 0.056, respectively). For female subjects with overweight/obesity, the serum triglyceride levels in MTHFR 677TT genotype [1.09 (0.78-1.50) mmol/L] were significantly higher as compared with MTHFR 677CC genotype [0.90 (0.60-1.15) mmol/L, P = 0.007], and the MTRR 66GG genotype carriers had higher serum high-density lipoprotein cholesterol levels than those with MTRR 66AG genotype (1.46 ± 0.50 vs. 1.19 ± 0.31 mmol/L, P = 0.058). Furthermore, in male subjects with overweight/obesity, the MTHFR 677CT genotype carriers had higher low-density lipoprotein cholesterol levels than those with MTHFR 677TT genotype (2.96 ± 1.07 vs. 2.74 ± 0.88 mmol/L, P = 0.015). CONCLUSIONS: Our results indicate that there exist interactive effects of the MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on some lipid traits in Chinese Han population, and the effects were gender-specific.

Interactions of Methylenetetrahydrofolate Reductase C677T Polymorphism with Environmental Factors on Hypertension Susceptibility.

Hypertension is considered to be the result of genes, environment, and their interactions. Among them age, sex, tobacco use, alcohol consumption, and being overweight/obesity are well documented environmental determinants, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is nominated as a potential genetic candidate. However, the synergistic effect of the MTHFR C677T polymorphism with these environmental factors on the risk of hypertension has received little attention. The aim of this study was to explore the associations of the MTHFR C677T polymorphism, environmental factors, and their interactions with hypertension predisposition in a Northern Chinese Han population. A total of 708 participants were enrolled in the study. The genotypes of the MTHFR C677T were determined by a TaqMan assay. We found that participants of an older age, being overweight/obesity, with a smoking habit, drinking habit, or carrying the 677T allele were at an increased risk of hypertension. Additionally, there existed marginally significant interactions of the polymorphism with age and overweight/obesity. However, future large, well-designed studies in Chinese and other populations, as well as mechanistic studies, are still needed to validate our findings, especially considering that the interactions observed in our study were only marginally significant.

Chronic Arsenic Poisoning Probably Caused by Arsenic-Based Pesticides: Findings from an Investigation Study of a Household.

In addition to naturally occurring arsenic, man-made arsenic-based compounds are other sources of arsenic exposure. In 2013, our group identified 12 suspected arsenicosis patients in a household (32 living members). Of them, eight members were diagnosed with skin cancer. Interestingly, all of these patients had lived in the household prior to 1989. An investigation revealed that approximately 2 tons of arsenic-based pesticides had been previously placed near a well that had supplied drinking water to the family from 1973 to 1989. The current arsenic level in the well water was 620 µg/L. No other high arsenic wells were found near the family's residence. Based on these findings, it is possible to infer that the skin lesions exhibited by these family members were caused by long-term exposure to well water contaminated with arsenic-based pesticides. Additionally, biochemical analysis showed that the individuals exposed to arsenic had higher levels of aspartate aminotransferase and γ-glutamyl transpeptidase than those who were not exposed. These findings might indicate the presence of liver dysfunction in the arsenic-exposed individuals. This report elucidates the effects of arsenical compounds on the occurrence of high levels of arsenic in the environment and emphasizes the severe human health impact of arsenic exposure.

Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects.

Several studies have examined the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with being overweight/obesity. However, the results are still controversial. We therefore conducted a case-control study (517 cases and 741 controls) in a Chinese Han population and then performed a meta-analysis by combining previous studies (5431 cases and 24,896 controls). In our case-control study, the MTHFR C677T polymorphism was not significantly associated with being overweight/obesity when examining homozygous codominant, heterozygous codominant, dominant, recessive and allelic genetic models. The following meta-analysis confirmed our case-control results. Heterogeneity was minimal in the overall analysis, and sensitivity analyses and publication bias tests indicated that the meta-analytic results were reliable. Similarly, both the case-control study and meta-analysis found no significant association between the MTRR A66G polymorphism and being overweight/obesity. However, sensitivity analyses showed that the associations between the MTRR A66G polymorphism and being overweight/obesity became significant in the dominant, heterozygous codominant and allelic models after excluding our case-control study. The results from our case-control study and meta-analysis suggest that both of the two polymorphisms are not associated with being overweight/obesity. Further large-scale population-based studies, especially for the MTRR A66G polymorphism, are still needed to confirm or refute our findings.

Use status and metabolism of realgar in Chinese patent medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar is widely used in combination with other herbs as Chinese patent medicine to treat a wide range of diseases in China. It is also a well known arsenical toxicant. Chronic arsenic poisoning events caused by long-term usage of realgar-containing medicines have been reported in literatures. Given to the paradoxical role of realgar, comprehensive outline of its usage status in Chinese patent medicine might provide basal data for evaluating its toxicology risks in populations. Unfortunately, the relevant information is limited. Also, a metabolic process after intake of realgar-containing medicine in humans is poorly understood. MATERIALS AND METHODS: The Traditional Chinese Patent Medicine Prescription Database was reviewed to get the information on the usage status of realgar. Realgar powder was dissolved in different pH-value solutions (1, 3, 5, 7, 9 and 11) to determine the soluble arsenic concentrations from realgar. Ten volunteers aged 24-26 years old were recruited to take four pills of Niu Huang Jie Du Pian (NHJDP), a very common Chinese patent medicine with realgar, to analyze the arsenic metabolism after exposure to realgar-containing medicine. The four pills were taken according to the medical instruction. Concentrations of soluble arsenic from realgar and urinary arsenic metabolites in humans were determined by hydride generation atomic absorption spectrometry. RESULTS: A total of 191 (2.25%) realgar-containing traditional Chinese patent medicines were obtained from the database, and almost 86.91% of them were for oral application. 73 (38.22%) medicines were found to be available for children. The mass fraction of arsenic in realgar-containing medicine ranged from 0.11% to 27.52%. According to medical instructions, the amount of average daily arsenic intake ranged from 0.47 to 2895.53mg. Nearly 86% medicines with daily intake of arsenic >10mg. Only inorganic arsenic (iAs) was detected from realgar in dissolution experiment and the levels of soluble iAs increased with pH values. After intake NHJDP, arsenic excretion in urine significantly increased, with a maximum excretion of iAs and monomethylarsonic acid at 6h post-ingestion and a peak excretion of dimethylarsinic acid at 9h post-ingestion. Arsenic methylation capacity was decreased after intake NHJDP. Females carried a more efficient arsenic methylation process than males. CONCLUSIONS: Realgar is widely used in traditional Chinese medicine. The arsenic solubility from realgar may be enhanced under alkaline conditions. The levels of urinary arsenic metabolites significantly increased while the arsenic methylation capacity significantly decreased after intaking realgar-containing medicine, which may suggest that a potential health hazard exists if people use arsenical medicines for long-term.

A potential synergy between incomplete arsenic methylation capacity and demographic characteristics on the risk of hypertension: findings from a cross-sectional study in an arsenic-endemic area of inner Mongolia, China.

Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects) residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%), primary methylation index (PMI) and secondary methylation index (SMI) were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI) and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors.

Association of lifetime exposure to fluoride and cognitive functions in Chinese children: a pilot study.

BACKGROUND: A systematic review and meta-analysis of published studies on developmental fluoride neurotoxicity support the hypothesis that exposure to elevated concentrations of fluoride in water is neurotoxic during development. METHODS: We carried out a pilot study of 51 first-grade children in southern Sichuan, China, using the fluoride concentration in morning urine after an exposure-free night; fluoride in well-water source; and dental fluorosis status as indices of past fluoride exposure. We administered a battery of age-appropriate, relatively culture-independent tests that reflect different functional domains: the Wide Range Assessment of Memory and Learning (WRAML), Wechsler Intelligence Scale for Children-Revised (WISC-IV) digit span and block design; finger tapping and grooved pegboard. Confounder-adjusted associations between exposure indicators and test scores were assessed using multiple regression models. RESULTS: Dental fluorosis score was the exposure indicator that had the strongest association with the outcome deficits, and the WISC-IV digit span subtest appeared to be the most sensitive outcome, where moderate and severe fluorosis was associated with a digit span total score difference of -4.28 (95% CI -8.22, -0.33) and backward score with -2.13 (95% CI -4.24, -0.02). CONCLUSIONS: This pilot study in a community with stable lifetime fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail.

Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China.

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.

Differences of urinary arsenic metabolites and methylation capacity between individuals with and without skin lesions in Inner Mongolia, Northern China.

Incomplete arsenic (As) methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%), the primary methylation index (PMI) and secondary methylation index (SMI) were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 µg/g Cr, p = 0.006) and MMA (69.34 vs. 42.85 µg/g Cr, p = 0.016) than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036) and SMI (0.74 vs. 0.81, p = 0.025) were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes mellitus in Chinese population: a meta-analysis of 29 case-control studies.

BACKGROUND: Methylenetetrahydrofolate 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. METHODS: We 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. RESULTS: 29 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. CONCLUSIONS: There 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.

The association between passive smoking and type 2 diabetes: a meta-analysis.

The number of people with diabetes has been exponentially increasing. A number of reports in the literature have suggested that exposure to passive smoke may play a key role in the development of diabetes; however, the association has not been jointly summarized yet. In this meta-analysis, 2 databases were searched to identify studies, and the references of these studies were scanned for further studies. Fourteen studies on the relationship between passive smoking and diabetes were included. After all the studies were pooled, the results showed that passive smoking was significantly associated with an increased risk of type 2 diabetes in a random model. The subgroup analysis results were consistent with overall results regardless of type of study design, age, gender, adjustment of dependent variables, area, or study quality. Sensitivity analysis indicated that the overall results were reliable. There was no publication bias observed in the selected studies.

Joint effects of urinary arsenic methylation capacity with potential modifiers on arsenicosis: a cross-sectional study from an endemic arsenism area in Huhhot Basin, northern China.

A lower arsenic methylation capacity is believed to be associated with various arsenic-related diseases. However, the synergistic effect of the arsenic methylation capacity and potential modifiers on arsenicosis risk is unclear. The current study evaluated the joint effect of the arsenic methylation capacity with several risk factors on the risk of arsenicosis characterized by skin lesions. In total, 302 adults (79 arsenicosis and 223 non-arsenicosis) residing in an endemic arsenism area in Huhhot Basin were included. Urinary levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of arsenic species (iAs%, MMA%, and DMA%), as well as two methylation indices (primary methylation index, PMI, and secondary methylation index, SMI), were calculated to assess the arsenic methylation capacity of individuals. The results showed that a lower methylation capacity, which is indicated by higher MMA% values and lower DMA% and SMI values, was significantly associated with arsenicosis after the adjustment for multiple confounders. The relative excess risk for interactions between higher MMA% values and older age was 2.35 (95% CI: -0.56, 5.27), and the relative excess risk for interactions between higher MMA% values and lower BMI was 1.08 (95% CI: -1.20, 3.36). The data also indicated a suggestive synergistic effect of a lower arsenic methylation capacity (lower DMA% and SMI) with older age, lower BMI, and male gender. The findings of the present study suggest that a lower arsenic methylation capacity was associated with arsenicosis and that certain risk factors may enhance the risk of arsenic-induced skin lesions.

Associations of MTHFR gene polymorphisms with hypertension and hypertension in pregnancy: a meta-analysis from 114 studies with 15411 cases and 21970 controls.

BACKGROUND: Several 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. METHODOLOGIES: The 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 FINDINGS: A 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. CONCLUSIONS: This meta-analysis suggests that the MTHFR C677T rather than A1298C polymorphism may be associated with H & HIP, especially among East Asians and Caucasians.