Low folate status, and MTHFR 677C > T and MTR 2756A > G polymorphisms associated with colorectal cancer risk in Thais: a case-control study.

Folate plays essential roles in DNA synthesis, repair, and methylation; thus, folate status may affect carcinogenesis. Genetics polymorphisms involved in folate metabolisms have been linked with colorectal cancer (CRC) development. Therefore, we hypothesized that low folate status and related genetic polymorphisms are associated with higher risk of CRC. This case-control study enrolled 105 new cases of CRC, 101 of colorectal adenoma (CRA), and 182 controls from hospitals in Bangkok, Thailand, to examine the association between folate status and methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine synthase (MTR) 2756A > G, and methionine synthase reductase (MTRR) 66A > G with the risk of CRC and CRA. Regarding CRC risk, the lowest quartile group of serum folate and folate intake had higher risk of CRC than the highest quartile group (odds ratio [OR] = 11.45, 95% confidence interval [CI] = 4.43-29.59) and (OR = 10.29, 95% CI = 4.17-25.41). The lowest quartile group of folate intake also had a higher risk of CRA (OR = 5.22, 95% CI = 2.19-6.09). Low red blood cell folate combined with MTHFR 677C > T polymorphism statistically increased CRC risk (OR = 10.00, 95% CI = 1.36-73.42). Low folate status combined with MTR 2756A > G significantly increased CRA risk (OR = 6.43, 95% CI = 1.38-29.94). Moreover, the risk of CRC was elevated with alcohol consumption and low exercise activity when combined with low folate status (P < .05). This study supported the hypothesis that, in Thais, low folate status is associated with a higher risk of CRC, particularly among those with polymorphisms of the MTHFR 677C > T and MTR 2756 A > G genes.

Association of Tumor Necrosis Factor Alpha, Interleukin 6, and C-Reactive Protein with the Risk of Developing Type 2 Diabetes: A Retrospective Cohort Study of Rural Thais.

The linkage of obesity, inflammation, and type 2 diabetes mellitus (T2DM) has been extensively investigated for over a decade. However, the association between inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α), and T2DM is still inconsistent and limited. Thus, this study is aimed at elucidating the association between inflammatory marker levels and the risk of developing T2DM in many aspects. Among 296 subjects enrolled in 2013, 248 non-T2DM subjects who were completely reinvestigated in 2014 and 2015 were included in a 2-year retrospective analysis. Multivariate logistic regression was performed to evaluate the association of baseline inflammatory marker levels and variation with incidence of T2DM. After the 2-year follow-up, 18.6% of total subjects had developed T2DM. The risk of developing T2DM was significantly increased in subjects with a high level of baseline CRP (OR = 4.02, 95% CI: 1.77-9.12, P = 0.001), and a stronger impact was found with the combination of high CRP and IL-6 levels (OR = 5.11, 95% CI: 1.27-20.49, P = 0.021). One-year inflammatory marker variation analysis also revealed the significant association of elevated TNF-α and risk of developing T2DM (OR = 4.88, 95% CI: 1.01-23.49, P = 0.048). In conclusion, besides consideration of CRP levels alone, our findings suggested that IL-6 outstandingly plays a contributing role in T2DM progression and elevated TNF-α levels over time could be a potential predictor of T2DM.

Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk.

BACKGROUND: Retinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand. METHODS: We measured the serum RBP4, TTR, glucose, triglyceride and insulin levels, and glucose tolerance of 167 volunteers from Sung Noen District, Nakhon Ratchasima Province, Thailand. Student's t-test, Pearson's correlation and logistic regression analysis were used to evaluate the relationships between RBP4, TTR and type 2 diabetes markers. RESULTS: RBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r = 0.26, p < 0.01) levels, as well as HOMA-IR values (r = 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95% CI =1.42-9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95% CI = 1.30-9.20, p = 0.01) and 3.6 (95% CI = 1.33-9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r = 0.18, p < 0.05), but not found this relationship in RBP4. CONCLUSIONS: The associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.

Elevated C-reactive protein, interleukin 6, tumor necrosis factor alpha and glycemic load associated with type 2 diabetes mellitus in rural Thais: a cross-sectional study.

BACKGROUND: The elevated levels of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL6) are supposed to be associated with type 2 diabetes mellitus (T2DM). Frequent high glycemic load (GL) consumption, central obesity, and a lack of physical activity are considered to be T2DM risk factors. This study aimed to determine the difference of these inflammatory markers as well as GL in individuals with versus those without T2DM in rural Thais. METHODS: A total of 296 participants aged 35-66 living in Sung Noen District, Nakhon Ratchasima Province, Thailand, were recruited. Blood was collected to evaluate blood glucose levels, lipid profiles, and inflammatory markers. A Semi-food frequency questionnaire was utilized to assess GL followed by socioeconomic and anthropometric assessment. Statistical analysis was subsequently performed. RESULTS: Elevated CRP and IL6 levels were associated with increased risk of developing T2DM [OR (95% CI): 7.51 (2.11, 26.74) and 4.95 (1.28, 19.11)], respectively. There was a trend towards increased risk of T2DM with elevated TNF-α levels [OR (95% CI): 1.56 (0.39, 6.14)]. GL correlated significantly with fasting blood glucose (r = 0.289, P = 0.016), suggesting that it is involved in T2DM in this study group. CONCLUSION: In this study, CRP, IL6, and TNF-α associated with T2DM. Our findings suggested that these inflammatory markers, especially CRP, may initiate T2DM.