Interleukin-6 gene polymorphisms correlate with the progression of nephropathy in Chinese patients with type 2 diabetes: A prospective cohort study.

AIMS: Interleukin-6 (IL-6), an inflammatory cytokine, is considered a candidate gene possibly involved in susceptibility to nephropathy in diabetes. This study aimed to examine whether IL-6 polymorphisms predict the progression of nephropathy in a prospective Chinese cohort of patients with type 2 diabetes. METHODS: A total of 568 type 2 diabetic patients with normoalbuminuria at baseline were followed up for a mean of 5.3±1.5years. Urinary albumin-to-creatinine ratio (ACR) ⩾30mg/g in two consecutive urine tests were defined as progression to diabetic nephropathy (n=143). Five polymorphisms of IL-6 gene, rs1800795, rs1800796, rs1524107, rs2069837, and rs2069840, were genotyped. Cox proportional hazard models were used to estimate hazard ratio (HR) and 95% CI of progression to diabetic nephropathy under different genetic models. RESULTS: Almost all patients (99.6%) carried the rs1800795 GG homozygous genotypes. In the Cox proportional models adjusted for multiple covariates, the HR under recessive model was 2.02 for rs1800796 GG (vs. CC+CG, 95% CI: 1.08-3.75, p=0.027), 2.37 for rs2069837 GG (vs. AA+AG, 95% CI: 1.15-4.87, p=0.019), and 2.08 for rs1524107 CC (vs. TT+TC, 95% CI: 1.12-3.89, p=0.021). These associations remained significant for rs1800796 and rs1524107 after correction for multiple testing (α=0.017). Overall, our results suggest that rs1800796 GG and rs1524107 CC homozygous genotypes may confer a greater risk for development of nephropathy in type 2 diabetes. CONCLUSIONS: IL-6 gene polymorphisms rs1800796 and rs1524107 may serve as predictors of progression of nephropathy in Chinese patients with type 2 diabetes.

High serum folate might have a potential dual effect on risk of colorectal cancer.

BACKGROUND & AIMS: The possible dual role of serum folate in the development and progression of colorectal cancer (CRC) has not been well established in human studies. This study investigated the association between serum folate and the risk of CRC in subjects with CRC or colorectal adenomatous polyps (AP, a precursor of CRC), and healthy subjects. METHODS: This study has a case-control design. Two hundred and thirty-seven men and 171 women were recruited with 156 subjects in the CRC group, 70 subjects in the AP group and 182 healthy subjects in the control group. RESULTS: The risk of CRC was significantly increased in the third (OR, 3.46; 95% CI, 1.16-10.34) and fourth (OR, 4.86; 95% CI, 1.42-16.58) quartiles of serum folate concentration after adjusting for potential confounders among subjects with AP or CRC. Furthermore, serum folate concentration had no significant effect on the risk of CRC among subjects in the control and CRC groups. CONCLUSIONS: Higher serum folate concentration was significantly correlated with increased CRC risk in subjects with AP, while serum folate had no effect on CRC risk in healthy controls. Serum folate might possess potential dual modulatory effects on the risk of CRC.

The metabolic syndrome is associated with an increased risk of colorectal polyps independent of plasma homocysteine.

BACKGROUND/AIMS: The links between the metabolic syndrome and homocysteine in relation to the risk of colorectal polyps are not understood. The purpose of this study was to investigate the association between the metabolic syndrome and homocysteine and further analyze the relationship between these two factors and the risk of colorectal polyps. METHODS: This was a case-control study. A total of 135 participants with colorectal polyps (cases) and 110 participants without polyps (controls) were recruited. RESULTS: There were 59 participants with the metabolic syndrome in the case group and 36 participants with the metabolic syndrome in the control group. The metabolic syndrome and its individual components, except for serum triglycerides, and homocysteine were associated with the risk of colorectal polyps. When the association of the metabolic syndrome and homocysteine with the risk of colorectal polyps was simultaneously considered, the association between homocysteine and the risk of colorectal polyps disappeared, but waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, and the metabolic syndrome itself were still significant risk factors for the development of colorectal polyps. CONCLUSION: Although the metabolic syndrome and plasma homocysteine were individually related to the risk of colorectal polyps, the metabolic syndrome was a major contributing factor in relation to the risk of colorectal polyps independent of plasma homocysteine.

Higher plasma homocysteine is associated with increased risk of developing colorectal polyps.

Colorectal adenomas are considered to be precursors of colorectal cancer. B-vitamins (i.e., folate, vitamin B(6) and B(12)) are involved in homocysteine metabolism and play an important role as coenzymes in 1-carbon metabolism, which is thought to have a critical role in the progression of colorectal polyps. The purpose of this study was to examine the effects of B-vitamins and homocysteine on the risk of developing colorectal polyps. Forty-eight participants with colorectal polyps [29 adenomatous polyps (AP), 19 hyperplastic polyps (HP)], and 96 age- and sex-matched healthy controls were recruited. Fasting blood was drawn from each participant to measure hematological parameters, plasma pyridoxal 5'-phosphate (PLP), serum folate and vitamin B(12), and plasma homocysteine. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy controls. There was no significant difference in serum folate and vitamin B(12) and plasma PLP among the 3 groups. B-vitamins had no significant effect on the risk of colorectal polyps. However, participants with higher plasma homocysteine [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.13, 3.08) level exhibited significantly increased risk of colorectal polyps after adjusting for potential confounders. Plasma homocysteine was a strong predictor of the risk of colorectal polyps in participants with adequate B-vitamins status.