Potential causal associations between vitamin D and uric acid: Bidirectional mediation analysis.

Vitamin D deficiency, a major public-health worldwide, is associated with hyperuricemia but casual association is questioned. The study was conducted to determine potential causal associations between 25-hydroxy vitamin D (25(OH)D) and uric acid (UA). A cross-sectional study of the Electricity Generating Authority of Thailand (EGAT3) cohort was conducted. Subjects (n = 2,288) were used to genotype the group-specific component (GC) at rs2282679 and ATP-binding cassette subfamily G member 2 (ABCG2) at rs2231142. Mediation analysis with 1000-replication bootstrap was applied to construct causal pathways i.e., rs2282679 → 25(OH)D → UA and rs2231142 → UA → 25(OH)D: The mediator (i.e., 25(OH)D and UA) was firstly regressed on the studied gene (i.e., rs2282679 and rs2231142). A potential causal effect of C allele on UA through 25(OH)D was -0.0236 (95% CI: -0.0411, -0.0058), indicating every minor C allele resulted in decreasing the 25(OH)D and then significantly decreased the UA by 0.0236 unit. For the second pathway, the mediation effect was 0.0806 (95% CI: 0.0107, 0.1628); every T allele copy for rs2231142 increased UA and thus increased 25(OH)D by 0.0806 unit. Our study suggested potential causal associations between the GC gene and UA through the 25(OH)D mediator, and the ABCG2 and the 25(OH)D through the UA mediator but the absolute effects are very clinically small.

Relationship of vitamin D status and bone mass according to vitamin D-binding protein genotypes.

BACKGROUND: Vitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers. METHODS: This cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1-L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry. RESULTS: The DBP rs2282679 genotype distribution conformed to the Hardy-Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI. CONCLUSIONS: The interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD.

Causal relationship between body mass index and fetuin-A level in the asian population: a bidirectional Mendelian randomization study.

OBJECTIVE: Fetuin-A is associated with body mass index (BMI) as well as components of the metabolic syndrome. However, it is unclear if fetuin-A affects BMI or the other way around. We therefore assessed the causal association between fetuin-A and BMI or vice versa, utilizing a bidirectional Mendelian randomization approach. DESIGN AND METHODS: This was a study of 2558 subjects from the Electricity Generating Authority of Thailand (EGAT) cohort. Two polymorphisms, that is, rs2248690 in the alpha2-Hereman-Schmid glycoprotein (AHSG) gene and rs9939609 in the fat mass and obesity-associated (FTO) gene were genotyped. Bidirectional causal models were constructed using a two-stage least-square instrumental variable (IV) regression. First, rs2248690 locus was used as the instrumental variable for the effect of circulating fetuin-A on BMI, and then, the FTO rs9939609 locus was used as the instrumental variable for the effect of BMI on circulating fetuin-A. RESULTS: Among the 2558 subjects, the prevalence of the minor AHSG (T) and FTO (A) alleles was 17.9% and 22.1%, respectively. The AHSG rs2248690 locus was highly related to serum fetuin-A levels (P < 0.001). Likewise, the FTO rs9939609 locus and BMI were highly associated (P < 0.001). Mendelian randomization analyses showed that circulating fetuin-A, instrumented by the AHSG rs2248690 locus, was associated with BMI (coefficient = 2.26; 95% CI: 0.39, 4.12). In contrast, BMI, instrumented by the FTO rs9939609 locus, was not associated with circulating fetuin-A (coefficient = 0.0007; 95% CI: -0.0242, 0.0256). CONCLUSION: Our findings suggest a causal association leading from circulating fetuin-A to BMI. There was no evidence of reverse causality from BMI to fetuin-A.

Association between inflammatory marker, environmental lead exposure, and glutathione S-transferase gene.

A number of studies suggested that lead is related to the induction of oxidative stress, and alteration of immune response. In addition, modifying these toxic effects varied partly by GST polymorphism. The objectives of this study were to assess the association between the lead-induced alteration in serum hs-CRP, with GSTM1, GSTT1, and GSTP1 Val105Ile genetic variations and the health consequence from environmental lead exposure. The 924 blood samples were analyzed for blood lead, CRP, and genotyping of three genes with real-time PCR. Means of blood lead and serum hs-CRP were 5.45 µ g/dL and 2.07 mg/L. Both CRP and systolic blood pressure levels were significantly higher for individuals with blood lead in quartile 4 (6.48-24.63 µ g/dL) compared with those in quartile 1 (1.23-3.47 µ g/dL, P < 0.01). In particular, in men with blood lead >6.47 µ g/dL the adjusted odds ratio (OR) of CRP levels for individuals with GSTP1 variants allele, GSTM1 null, GSTT1 null, double-null GSTM1, and GSTT1 compared with wild-type allele was 1.46 (95% CI; 1.05-2.20), 1.32 (95% CI; 1.03-1.69), 1.65 (95% CI; 1.17-2.35), and 1.98 (95% CI; 1.47-2.55), respectively. Our findings suggested that lead exposure is associated with adverse changes in inflammatory marker and SBP. GST polymorphisms are among the genetic determinants related to lead-induced inflammatory response.

Validity of the Thai EQ-5D in an occupational population in Thailand.

PURPOSE: To assess the construct validity of the Thai EuroQoL (EQ-5D) among an occupational population in Thailand. METHODS: Data were derived from a large cohort study among employees of the Electricity Generating Authority of Thailand. In 2008 and 2009, 4,850 participants completed the Thai EQ-5D and Short-Form 36 version 2 (SF-36v2). Thai preferences weights were used to convert EQ-5D health states into EQ-5D index scores. Construct validity of the Thai EQ-5D was examined by specifying and testing hypotheses about the relationships between the EQ-5D, SF-36v2, and participants' demographic and medical characteristics. RESULTS: Construct validity of the Thai EQ-5D was supported by expected relationships with SF-36v2 scale and summary scores. For example, SF-36v2 scores on the mental health scale were much lower for participants who reported having problems on the EQ-5D anxiety/depression dimension compared to those reporting no problems (mean norm-based SF-36v2 scores: 52.9 vs. 41.8, p < 0.001). Additionally, reporting a problem in a given EQ-5D dimension was generally associated with lower SF-36v2 summary scores. The EQ-5D index score distinguished between groups of participants in the expected manner, on the basis of sex, age, education and self-reported health, thus providing evidence of known-groups validity. CONCLUSION: The study demonstrated good construct validity of the Thai EQ-5D in a large occupational population in Thailand.

Serum uric acid levels in relation to bone-related phenotypes in men and women.

Serum uric acid levels have recently been found to be associated with bone mineral density (BMD) in elderly males. The purpose of the present study was to investigate the relationship between bone-related phenotypes and serum uric acid levels in young and middle-aged males and females. Subjects consisted of 1320 males and 485 females aged 25-54 yr. Bone densitometry and quantitative ultrasonometry (QUS) were performed on each subject. Serum uric acid and biochemical markers of bone turnover were measured in fasting serum samples. When adjusted for covariates including age, body weight, and serum creatinine in multiple linear regression models, it was found that there was a positive association between uric acid levels and BMD in males at the lumbar spine (p < 0.05). The association between uric acid levels and BMD was found in females after controlling for age, body weight, and serum creatinine at the femoral neck, but in the opposite direction (p < 0.05). Uric acid levels were related to the stiffness index (SI) as assessed by QUS in males, independent of age, body weight, and serum creatinine (p < 0.05). No association between uric acid and SI in females was found. The present study demonstrated a positive association in males between serum uric acid levels and BMD, and SI from QUS, suggesting a beneficial influence of uric acid on both the quantity and quality of bone in males.

Causal inference of the effect of adiposity on bone mineral density in adults.

OBJECTIVE: The causal effect of adipose tissue on bone mass and the direction of its net influence have not been directly assessed in adult humans. Using the Mendelian randomization analysis, we assessed the causality of adiposity in measurements of bone mass in adult males and females. DESIGN AND METHODS: Subjects consisted of 2154 adults aged 25-54 years from a cross-sectional cohort of the employees of the Electricity Generating Authority of Thailand. Body composition was determined after at least 3 h of fasting using multifrequency bioelectrical impedance analysis. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. A polymorphism in the fat mass and obesity-associated gene (FTO rs9939609) was used as an instrument in the Mendelian randomization analysis. RESULTS: The genotype distribution of the FTO rs9939609 polymorphism was 61·1% TT, 33·9% AT and 5·0% AA. The average body mass index (BMI), body fat mass and percentage body fat were 23·9 kg/m(2) (SD = 3·6), 17·9 kg (SD = 6·6) and 26·8% (SD = 7·2), respectively. The FTO rs9939609 polymorphism was significantly correlated with BMI (coefficient = 0·673 kg/m(2) , P < 0·001), body fat mass (coefficient = 0·948 kg, P < 0·001) and percentage body fat (coefficient = 0·759%, P < 0·01). An instrumental variable (IV) regression model, using BMI as the intermediate phenotype, suggested that FTO was a strong IV. Also, the FTO-BMI polymorphism was significantly associated with total hip and femoral neck BMD but was not correlated with total spine BMD, with estimated correlation coefficients of 0·0189 (95% CI: 0·0046, 0·0332), 0·0149 (95% CI: 0·0030, 0·0268) and 0·0025 (95% CI: -0·0131, 0·0136) g/cm(2) , respectively. The variances of BMDs explained by the FTO-BMI were 19·0%, 21·3% and 1·1%, respectively. Similar trends were also observed for the FTO-body fat mass and FTO-percentage body fat correlations. CONCLUSIONS: Mendelian randomization analysis suggests that adiposity might be causally related to BMD at the femur but not at the spine.

Association between cigarette smoking and the intraoral distribution of periodontal disease in Thai men over 50 years of age.

AIM: This study aimed to investigate the effects of cigarette smoking on periodontal conditions in specific tooth regions of older Thai men. METHODS: There were 272 current smokers, 714 former smokers, and 477 non-smokers enrolled in the present study. Differences between groups in the mean probing depth or attachment loss were compared using ancova. The relationship between smoking exposure or cessation duration and periodontal conditions was examined using linear trend analysis. RESULTS: Smokers had deeper pockets and attachment loss than non-smokers. The greatest differences between smokers and non-smokers were observed in the maxillary posterior palatal region, where current smokers had 0.88 mm greater attachment loss than non-smokers, compared to 0.36-0.60 mm observed in other tooth regions. Among the current smokers, there was a trend towards an increase in attachment loss with increasing smoking exposure in the maxillary posterior regions. However, it was not statistically significant. Among the former smokers, a better periodontal condition was observed, depending on the length of time since smoking cessation; this was most pronounced in the maxillary posterior palatal region. CONCLUSIONS: The palatal site of maxillary posterior teeth was the area most affected by cigarette smoke. The results suggest a possible local effect of smoking in addition to its systemic effects.

Blood pressure, cholesterol and cardiovascular disease in Thailand.

BACKGROUND: Although associations between risk factors such as hypertension and hypercholesterolaemia, and cardiovascular disease (CVD) are well-established it is not known to what extent these associations are similar in people from different ethnicities or regions. This study aims to measure the contributions of systolic blood pressure (SBP) and total cholesterol (TC) to ischaemic heart disease (IHD) and stroke in the Thai population. METHODS AND RESULTS: Data from a Thai cohort study were used for analyses. Participants were 2702 males and 797 females aged between 35 and 54 years at the start of study in 1985. Cox Proportional Hazards Models were used to assess RRs of IHD or stroke associated with SBP or TC stratified by age at the time of an event of 30-44, 45-59, and 60-69 years. During the 17 years of follow-up, 96 IHD (40 non-fatal, 56 fatal), 69 strokes (32 non-fatal and 37 fatal) occurred. Each 1 mmol/l increase in TC was associated with a fivefold increase in IHD risk in people aged 30-44 years, but not with significant increase in stroke risk in any age group. The RRs (95% CIs) of IHD per 10 mm Hg increase in SBP were 1.31 (1.04 to 1.64) and 1.46 (1.15 to 1.87), and of stroke, 1.40 (1.10 to 1.79) and 1.85 (1.40 to 2.45) in people aged 45-59 and 60-69 years, respectively. CONCLUSIONS: Increases in IHD and stroke risks associated with these two risk factors observed in Thailand are comparable with those in the Asia Pacific and western populations.

Associations between serum lipids and causes of mortality in a cohort of 3,499 urban Thais: The Electricity Generating Authority of Thailand (EGAT) study.

The association between serum lipids and mortality has not previously been established in Thailand. Baseline data from the Electricity Generating Authority of Thailand (EGAT) cohort study, plus a resurvey of the cohort 15 years later were analyzed. Participants were employees of EGAT: 2,702 men and 797 women. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were taken as predictive variables; age, sex, hypertension, diabetes, cigarette smoking, alcohol drinking, and body mass index were taken as confounders. Dependent variables were all-causes and specific causes of mortality over 17 years of follow-up. The major cause of death among men was cardiovascular disease (CVD); among women, it was cancer. Relative risks (RR) for specific causes of death, for a mmol/L increase in each lipid, were estimated after adjustment for confounding factors using Cox proportional hazards regression. TC and LDL-C were negatively associated with liver cirrhosis mortality, although it was likely that the low cholesterol concentration was a consequence of the disease. HDL-C was negatively associated with CVD mortality (RR = 0.59; 95% confidence interval [CI], 0.39-0.93), coronary heart disease (CHD) mortality (RR = 0.36; 95% CI, 0.17-0.75) and all cause-mortality (RR = 0.68; 95% CI, 0.54-0.87). TG was not associated with mortality. HDL-C is an important risk factor for CVD in middle-class urban Thais. Health promotion programs to improve lipid profiles, such as effective exercise campaigns and dietary advice, are required to increase HDL-C and to help prevent CVD and premature death in Thailand.