Is bisphenol A exposure associated with the development of glucose intolerance and increased insulin resistance in Thais?

Bisphenol A (BPA), the monomeric component of polycarbonate plastics, reportedly possesses endocrine-disrupting effects. Exposure to low levels of BPA during more vulnerable periods leads to abnormalities related to sexual development in experimental animals. Moreover, recently a few epidemiological studies in Caucasians have demonstrated the association of BPA exposure with type 2 diabetes. Therefore, in the present study we examined the association of BPA exposure and abnormal glucose tolerance in Thais. This is a cross-sectional study of 240 participants aged at least 50 years, randomly selected by computer-generated random numbers within each glucose tolerance status from an oral glucose tolerance study of 661 participants. There were 80 participants in each group of type 2 diabetes, impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). Serum BPA was measured by competitive ELISA. The detection rate of BPA was significantly higher in participants with IGT compared to those with NGT ( p < 0.05), while no difference was found between participants with type 2 diabetes and NGT. When participants with type 2 diabetes were stratified into those with fasting plasma glucose (FPG) under the diabetic threshold (<126 mg/dL) and those over (≥126 mg/dL), it was found that those with FPG under the diabetic threshold had measurable rates of BPA comparable to those with IGT, and rates significantly higher than the NGT group ( p < 0.05), while those with FPG over the diabetic threshold did not have higher rates of measurable BPA compared with the NGT group. In conclusion, BPA exposure is not uncommon in Thais. There is an association between BPA exposure and IGT, but not type 2 diabetes.

Vitamin D status is a determinant of skeletal muscle mass in obesity according to body fat percentage.

OBJECTIVES: Vitamin D deficiency is now being recognized as an emerging problem worldwide. Obesity has been found to be associated with lower serum 25-hydroxyvitamin D [25(OH)D] concentrations due to various mechanisms. There is increasing evidence showing the extraskeletal health benefit of vitamin D. Previous studies demonstrated the relationship between vitamin D and adiposity. However, the association between vitamin D status and skeletal muscle mass has not been established in healthy obese individuals in tropical countries. The aim of this cross-sectional study was to assess vitamin D status and its relationship to serum 25(OH)D concentrations and body composition, including skeletal muscle mass (SMM) and adiposity in healthy obese individuals without diabetes who live in Thailand, which is located near the equator. METHODS: We enrolled 163 obese Thai individuals (59.5% women) from the obesity clinic at the Ramathibodi Hospital, Mahidol University, in Bangkok, Thailand. RESULTS: The prevalence of vitamin D deficiency (<20 ng/mL) and vitamin D inadequacy (<30 ng/mL) were 49 (30.1%) and 148 (90.8%), respectively. In all, 98% of the individuals with body mass index >35 kg/m(2) had vitamin D inadequacy. Serum 25(OH)D concentrations were negatively associated with percent body fat (%BF) (r = -0.23; P = 0.003). Moreover, vitamin D status was positively associated with SMM (r = 0.18; P = 0.03) and the association remained after controlling for body fat mass and age (P = 0.003). Interestingly, in the individuals with lowest tertile of %BF, multiple linear regression analysis revealed that the significant positive predictors of %SMM were vitamin D status and male sex; the negative predictor was the body mass index after adjusting for age and exercise duration. CONCLUSIONS: Our study demonstrated the high prevalence of vitamin D deficiency in obese, Thai populations without diabetes. Vitamin D status was an independent predictor of %SMM of patients with lowest tertile of %BF. We speculated that adiposity might play a role in the relationship of vitamin D and SMM.

Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2supplementation.

BACKGROUND: It is not known whether genetic variation in the vitamin D binding protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D3 and 25(OH)D2 in a Thai cohort, according to type of vitamin D supplement (vitamin D3 or D2) and DBP genotype, after receiving vitamin D3 or D2 for 3 months. METHODS: Thirty-nine healthy subjects completed the study. All subjects received 400 IU of either vitamin D3 or D2, plus a calcium supplement, every day for 3 months. Total serum 25(OH)D, 25(OH)D3 and 25(OH)D2 were measured by LC-MS/MS. Individual genotyping of rs4588 in the DBP gene was performed using real-time PCR. RESULTS: Vitamin D3 supplementation of 400 IU/d increased 25(OH)D3 significantly (+16.2 ± 4.2 nmol/L, p <0.001). Vitamin D2 (400 IU/d) caused increased 25(OH)D2 levels (+22.0 ± 2.11 nmol/L, p <0.001), together with a decrease of 25(OH)D3 (-14.2 ± 2.0 nmol/L, p <0.001). At 3 month, subjects in vitamin D3 group tended to have higher total 25(OH)D levels than those in vitamin D2 (67.8 ± 3.9 vs. 61.0 ± 3.0 nmol/L; p = 0.08). Subjects were then classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and the rest (CA or AA). With D3 supplementation, subjects with CA or AA alleles had significantly less increase in 25(OH)D3 and total 25(OH)D when compared with those with the CC allele. However, no difference was found when the supplement was vitamin D2. CONCLUSION: Genetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D3 but not vitamin D2.

A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis.

Several lines of evidence have pointed out that genetic components have roles in thyrotoxic hypokalemic periodic paralysis (TTPP). In this study, for the first time we performed genome-wide association study (GWAS) in male hyperthyroid subjects in order to identify genetic loci conferring susceptibility to TTPP. We genotyped 78 Thai male TTPP cases and 74 Thai male hyperthyroid patients without hypokalemia as controls with Illumina Human-Hap610 Genotyping BeadChip. Among the SNPs analyzed in the GWAS, rs312729 at chromosome 17q revealed the lowest P-value for association (P=2.09 × 10(-7)). After fine mapping for linkage disequilibrium blocks surrounding the landmark SNP, we found a significant association of rs623011; located at 75 kb downstream of KCNJ2 on chromosome 17q, reached the GWAS significance after Bonferroni's adjustment (P=3.23 × 10(-8), odds ratio (OR)=6.72; 95% confidence interval (CI)=3.11-14.5). The result was confirmed in an independent cohort of samples consisting of 28 TTPP patients and 48 controls using the same clinical criteria diagnosis (replication analysis P=3.44 × 10(-5), OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71 × 10(-12), OR=5.47; 95% CI=3.04-9.83).

Association of genetic variants in GABRA3 gene and thyrotoxic hypokalaemic periodic paralysis in Thai population.

BACKGROUND: Genetic predisposition has been suggested to play role in the pathogenesis of thyrotoxic hypokalaemic periodic paralysis (THPP). OBJECTIVES: In this study, we assessed the differences of single-nucleotide polymorphisms (SNP) allelic frequency between THPP patients and well-characterized controls in order to find the susceptibility genetic variants related to THPP using microarray-based assessments on pooled DNA. METHODS: Fifty cases of THPP and 50 male hyperthyroid patients without hypokalaemia as controls were recruited. Equal amounts of individual genomic DNA were pooled from each group. Estimated allele frequencies of SNPs were derived by averaging relative allele signal score obtained by Affymetrix GeneChip(R) Mapping 10K Arrays. RESULTS: Sixty-nine loci that display robust allele frequency differences between THPP and controls were identified. SNP rs750841 (A > T) in intron 3 of the gamma-aminobutyric acid (GABA) receptor alpha3 subunit (GABRA3) gene possessed the most significant difference in allele frequency (27% in THPP case and 5% in controls, P = 0.007). Actual allele frequencies obtained from genotyping in each individual were very similar to the estimated frequency from the pools (28% in THPP and 2% in controls, and P = 0.0002). Nearby DNA sequences of GABRA3 were sequenced and an additional two SNPs were found (A > C at exon 1 and G > T of rs12688128). Allele A of rs750841 and allele G of rs12688128 in intron 3 were predominantly found in THPP with significant genetic relative risk of 19 (P < 0.0002; 95%CI 2.4-151.6). CONCLUSIONS: Whole-genome scanning on pooled DNA provides an accurate, useful screening tool for elucidating genetic underpinnings of THPP. SNPs at intron 3 of GABRA3 are found to be associated with THPP.