Independent and Opposite Associations Between Branched-Chain Amino Acids and Lysophosphatidylcholines With Incident Diabetes in Thais.

Branched-chain amino acids (BCAAs) and lysophosphatidylcholines (LPCs) have been reported to be associated with diabetes. The purpose of the present study was to investigate the relative contributions of BCAAs and LPCs to the progression of prediabetes to diabetes using a targeted metabolomic approach. This study was part of a health survey of employees of the Electricity Generating Authority of Thailand (n = 79; nine females and 70 males). A targeted metabolomics analysis was performed using an AbsoluteIDQ® p180 kit, flow injection analysis, and liquid chromatography-tandem mass spectrometry. The highest variable importance in projection (VIP) scores for the progression to diabetes of the amino acids and phospholipids were associated with isoleucine and LPC acyl C28:1, respectively. Using logistic regression analysis, we found that high baseline isoleucine concentration was associated with a higher incidence of diabetes, while high LPC acyl 28:1 was associated with a lower incidence. Isoleucine and LPC acyl 28:1 were independently associated with incident diabetes in a model that also included conventional risk factors for diabetes (baseline fasting plasma glucose (FPG), age, sex, and body mass index (BMI)). In addition, isoleucine and LPC acyl 28:1 were independently associated with serum HbA1c 5 years later in a robust regression model that also included baseline FPG, age, sex, and BMI. Isoleucine, LPC acyl 28:1, age, and FPG were significantly associated with HbA1c at this time. In conclusion, these results provide evidence that isoleucine and LPC acyl C28:1 have respective positive and negative independent associations with incident diabetes.

Environmental lead exposure, catalase gene, and markers of antioxidant and oxidative stress relation to hypertension: an analysis based on the EGAT study.

Lead has been linked to the development of hypertension via oxidative stress. Catalase plays an important role in the disposal of hydrogen peroxide in erythrocyte and its activity was determined by CAT gene. The aims of this study were to investigate (1) the association between blood levels of antioxidant markers such as catalase, superoxide dismutase, glutathione, glutathione peroxidase, oxidative stress-marker (malondialdehyde), and blood lead level and (2) the influence of genetic polymorphism of CAT gene (rs769217) on change in blood pressure in general population of EGAT study project. This is a cross-sectional study of 332 normotensive, 432 prehypertensive, and 222 hypertensive male subjects. Hypertensive subjects had significantly higher blood lead level (5.28 µg/dL) compared to normotensive (4.41 µg/dL) and prehypertensive (4.55 µg/dL) subjects (P < 0.05). These significant findings are also found in MDA levels. Moreover, individuals with TT genotype in hypertensive group had significantly higher blood lead and MDA levels (6.06 µg/dL and 9.67 µmol/L) than those with CC genotype (5.32 µg/dL and 8.31 µmol/L, P < 0.05). Our findings suggested that decreased blood catalase activity in this polymorphism together with low level lead exposure induced lipid peroxidation may be responsible for hypertension.

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.

Genetic variations of glutathione s-transferase influence on blood cadmium concentration.

The glutathione S-transferases (GSTs) are involved in biotransformation and detoxification of cadmium (Cd). Genetic polymorphisms in these genes may lead to interindividual variation in Cd susceptibility. The objective of this study was to assess the association of GSTs (GSTT1, GSTM1, and GSTP1 Val105Ile) polymorphisms with blood Cd concentrations in a nonoccupationally exposed population. The 370 blood samples were analyzed for Cd concentration and polymorphisms in GSTs genes. Geometric mean of blood Cd among this population was 0.46 ± 0.02 µg/L (with 95% CI; 0.43-0.49 µg/L). Blood Cd concentrations in subjects carrying GSTP1 Val/Val genotype were significantly higher than those with Ile/Ile and Ile/Val genotypes. No significant differences in blood Cd concentrations among individual with gene deletions of GSTT1 and GSTM1 were observed. GSTP1/GSTT1 and GSTP1/GSTM1 combinations showed significantly associated with increase in blood Cd levels. This study indicated that polymorphisms of GSTP1 combined with GSTT1 and/or GSTM1 deletion are likely to influence on individual susceptibility to cadmium toxicity.

Correlation between myocardial perfusion imaging findings and cardiac events.

OBJECTIVE: The excellent prognostic value of a normal or near normal stress myocardial perfusion imaging (MPI) has been confirmed in numerous studies. The aim of the present study was to determine the association of MPI findings and cardiac events. MATERIAL AND METHOD: Consecutive patients referred from January 2003 to December 2004 by Nuclear Medicine Unit in Ramathibodi Hospital for myocardial perfusion imaging were studied. Visual scoring of perfusion images used 17-segments and a scale of 0-4 was done. Sum stress score (SSS) was generated Cardiac death, death from any cause and nonfatal acute myocardial infarction (MI) were considered major cardiac events, and chest pain and late revascularization > 60 days after testing were considered minor cardiac events. RESULTS: Of the 320 patients studied, 218 subjects who had complete 1-year follow-up, were enrolled. There were 99 patients with normal MPI (SSS < or = 3) and 119 patients with abnormal MPI (SSS > 3). Statistical significance between cardiac events in two groups (p < 0.001) was detected. Among hard events, there were three cardiac deaths (of these, 1 occurred in a patient with normal MPI and 2 in those with abnormal MPI) and no patients had non-fatal MI in both groups. Among minor cardiac events, 17 patients developed chest pain and 11 patients underwent late revascularization. No patient with normal MPI underwent revascularization (included early and late revascularization) was found. CONCLUSION: These results show that SSS can be used to provide incremental prognostic information beyond clinical data, which confirms the conclusions drawn from the results of previous studies by using nuclear stress test results.