Association of plasma folate, vitamin B12 levels, and arsenic methylation capacity with developmental delay in preschool children in Taiwan.

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.

Plasma selenium influences arsenic methylation capacity and developmental delays in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in preschool children. Selenium has antioxidant and anti-inflammatory properties that protect experimental animals from chemically induced neurotoxicity. The present study was designed to explore whether plasma selenium levels affects arsenic methylation capacity related to developmental delay in preschool children. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 178 children with a developmental delay and 88 children without a delay were recruited. High-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry were used to determine urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV). Plasma selenium levels were measured by inductively coupled plasma mass spectrometry. As results, plasma selenium concentration was significantly inversely associated with the odds ratio (OR) of developmental delay. Plasma selenium concentration was positively associated with arsenic methylation capacity [percentage of inorganic arsenic and percentage of MMAV (MMAV%) decreased, and percentage of DMAV (DMAV%) increased]. High plasma selenium concentration and high DMA% significantly and additively interacted to decrease the OR of developmental delay; the OR and 95% confidence interval were 0.40 (0.18-0.90). This is the first study to show a combined dose-response effect of plasma selenium concentration and that efficient arsenic methylation capacity decreased the OR of developmental delay in preschool children.

Association of blood heavy metals with developmental delays and health status in children.

The aim of this study was to evaluate the association of blood lead, mercury, and cadmium concentrations with developmental delays and to explore the association of these concentrations with the health status of children. This study recruited 89 children with developmental delays and 89 age- and sex-matched children with typical development. Their health status was evaluated using the Pediatric Quality of Life (PedsQL) Inventory for health-related quality of life (HRQOL) and the Pediatric Outcomes Data Collection Instrument for function. Family function was also evaluated. Blood lead, mercury, and cadmium concentrations were measured using inductively coupled mass spectrometry. The children with developmental delays had a considerably poorer HRQOL, lower functional performance and family function, and a higher blood lead concentration than those with typical development. The blood lead concentration had a significantly positive association with developmental delays [odds ratio (OR) = 1.54, p < 0.01] in a dose-response manner, and it negatively correlated with PedsQL scores (regression coefficient: -0. 47 to -0.53, p < 0.05) in all the children studied. The higher blood cadmium concentration showed a significantly positive association with developmental delays (OR = 2.24, for >1.0 µg/L vs. <0.6 µg/L, p < 0.05). The blood mercury concentration was not associated with developmental delays and health status.

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity.

Association of Arsenic Methylation Capacity with Developmental Delays and Health Status in Children: A Prospective Case-Control Trial.

This case-control study identified the association between the arsenic methylation capacity and developmental delays and explored the association of this capacity with the health status of children. We recruited 120 children with developmental delays and 120 age- and sex-matched children without developmental delays. The health status of the children was assessed using the Pediatric Quality of Life Inventory (PedsQL) and Pediatric Outcomes Data Collection Instrument (PODCI). The arsenic methylation capacity was determined by the percentages of inorganic arsenic (InAs%), monomethylarsonic acid (MMAV%), and dimethylarsinic acid (DMAV%) through liquid chromatography and hydride generation atomic absorption spectrometry. Developmental delays were significantly positively associated with the total urinary arsenic concentration, InAs%, and MMAV%, and was significantly negatively associated with DMAV% in a dose-dependent manner. MMAV% was negatively associated with the health-related quality of life (HRQOL; -1.19 to -1.46, P < 0.01) and functional performance (-0.82 to -1.14, P < 0.01), whereas DMAV% was positively associated with HRQOL (0.33-0.35, P < 0.05) and functional performance (0.21-0.39, P < 0.01-0.05) in all children and in those with developmental delays. The arsenic methylation capacity is dose-dependently associated with developmental delays and with the health status of children, particularly those with developmental delays.

Arsenic methylation capacity and obesity are associated with insulin resistance in obese children and adolescents.

The goal of the present study was to compare the arsenic methylation capacities in elementary school and junior high school students in an area of Taiwan with low arsenic exposure, and explore the influence of both arsenic methylation capacity and obesity on insulin resistance in these children and adolescents using the HOMA-IR index. We recruited 303 elementary school students and 319 junior high school students in Taipei City from September 2007 to November 2011. Concentrations of inorganic arsenic (arsenite + arsenate), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were determined by a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Insulin resistance was determined by HOMA-IR. Elementary school students had significantly lower inorganic arsenic percentage and a higher DMA(V) percentage than junior high school students. It seems that the former had better arsenic methylation capability than the latter. The HOMA-IR value was significantly and positively related to the sum of the urinary inorganic and methylated arsenic (TotalAs) concentrations and also the BMI Z score, with the regression coefficients (ß) being 0.058 (p < 0.001) and 0.001 (p = 0.027), respectively. The higher BMI values and higher TotalAs concentration were associated with higher HOMA-IR values in children and adolescents in Taiwan.

Arsenic methylation capacity and developmental delay in preschool children in Taiwan.

Environmental exposure to lead or mercury can cause neurodevelopmental damage. Arsenic is another neurotoxicant that can affect intellectual function in children. This study was designed to explore the difference of arsenic methylation capacity indices between with and without developmental delay in preschool children. We also aimed to identify whether blood levels of lead or mercury modify the effect of arsenic methylation capacity indices. A cross sectional study was conducted from August 2010 to March 2012. All participants recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In all, 63 children with developmental delay and 35 children without developmental delay were recruited. Urinary arsenic species, including arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were measured with a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Lead and mercury levels of red blood cells were measured by inductively coupled mass spectrometry. All participants underwent developmental assessments to confirm developmental delays, including evaluations of gross motor, fine motor, speech-language, cognition, social, and emotional domains. Urinary total arsenic and MMA(V) percentage were significantly positively associated and DMA(V) percentage was negatively associated with the risk of developmental delay in a dose-dependent manner after adjustment for blood lead or mercury levels and other risk factors. A multivariate regression analysis indicated that blood lead level and arsenic methylation capacity each independently contributed to the risk of developmental delay. This is the first study to show that arsenic methylation capacity is associated with developmental delay, even without obvious environmental arsenic exposure.

Genetic polymorphisms of myeloperoxidase and their effect on hypertension.

Myeloperoxidase (MPO) is a member of the mammalian peroxidase superfamily and plays specific roles in host defense. This study aimed to explore the association between one polymorphism of MPO and hypertension risk. Study subjects were recruited from Taipei City Hospital, Zhongxiao Branch, Taipei Medical University Hospital and Taipei Municipal WanFang Hospital. Participants completed questionnaires and provided blood samples. In this study we considered hypertension to be present among subjects that had blood pressures above 140/90 mmHg, or who had previously received treatment for hypertension. The polymorphism of MPO investigated in this study was constructed by performing a restriction fragment length polymorphism following polymerase chain reaction. This study found the odds ratio and 95% confidence interval for hypertension among subjects with the MPO -463 GA/AA genotype to be 1.97 (1.23-3.16) when compared with those with the GG genotype after multivariate adjustment. Participants with a body mass index (BMI) ≥ 24 kg/m(2) and with MPO -463 GA/AA genotype had a 4.60-fold increased risk of hypertension compared with those with a BMI < 24 kg/m(2) and with the GG genotype. This is the first study to conclude that the MPO -463 GA/AA genotype was associated with hypertension. In addition, we also detected that subjects with the MPO -463 GA/AA genotype that had higher BMIs and positive diabetes status tended to have higher risks of hypertension than subjects with the MPO -463 GA/AA genotype that had normal BMIs and were not diabetic.

The relationship between obesity, insulin and arsenic methylation capability in Taiwan adolescents.

PURPOSE: This study evaluated the arsenic methylation profile of adolescents and explored the influence of body mass index (BMI) on the arsenic methylation profile of adolescents in an area of Taiwan with no-obvious arsenic exposure. METHODS: This study evaluated 202 normal weight students and 101 obese students from eight elementary schools, recruited from September 2009 to December 2009. Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA(5+)) and dimethylarsinic acid (DMA(5+)) were determined by a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. RESULTS: Urinary total arsenic was significantly decreased with increasing BMI, indicating that obese children may retain higher levels of arsenic in the body, as compared to normal weight children. Participants with obesity accompanied by high insulin levels had higher inorganic arsenic, significantly higher MMA percentage and significantly lower DMA percentage than those with obesity and low insulin levels. It seems children with obesity and high insulin levels had lower arsenic methylation capacity than those with obesity and low insulin. CONCLUSIONS: This is the first study to demonstrate that total urinary arsenic is negatively associated with the BMI in adolescents in Taiwan, adjusted for age and sex. Obese adolescents with high insulin levels had significantly higher MMA% and significantly lower DMA% than obese adolescents with low insulin.