Transcription factor 7-like 2 (TCF7L2) gene polymorphism and clinical phenotype in end-stage renal disease patients.

Variants of the transcription factor 7-like 2 gene (TCF7L2) have been associated with type 2 diabetes and cardiovascular disease in different populations. Here we investigated the potential association of the rs7903146 polymorphism in the TCF7L2 gene with clinical profile of end-stage renal disease (ESRD) patients. We examined a cohort of 1065 ESRD patients with diabetic and non-diabetic renal disease. The control group consisted of 924 healthy individuals. All subjects were genotyped for the rs7903146 single nucleotide polymorphism by polymerase chain reaction. The genotype distribution and allele frequencies were significantly different between ESRD patients and controls (p < 0.01). The OR for the TT genotype was 2.81 (95% CI 2.08-3.79). Genotype and allele frequencies were compared between subgroups of patients with different clinical phenotypes. The frequency of the T allele was significantly higher in patients with diabetic nephropathy versus non-diabetic renal disease (p = 0.007, OR 1.70, 95% CI 1.36-2.11). The statistically significant differences were demonstrated between patients with and without cardiovascular disease, with the OR for T allele 1.57 (95% CI 1.31-1.90). The odds ratio for TT genotype was 2.38 (95% CI 1.62-3.51). In our study the T allele of the rs7903146 SNP in the TCF7L2 gene confers the risk of developing diabetic nephropathy. We described for the first time a strong relationship between the TCF7L2 gene variant rs7903146 and cardiovascular disease in end-stage renal disease patients.

Calpain-10 gene polymorphisms in type 2 diabetes and its micro- and macrovascular complications.

Genetic variations in the calpain 10 gene (CAPN10) were previously implicated with increased risk of type 2 diabetes (T2DM). We studied the association of single nucleotide polymorphisms in the CAPN10 gene, SNP -43, SNP -19 and SNP -63, with T2DM and its complications. Overall, we examined 1440 individuals: 880 patients with diabetes and 560 healthy subjects, all Caucasians of Polish origin. All subjects were genotyped for the CAPN10 SNPs by polymerase chain reaction (PCR). The frequencies of alleles, genotypes and haplotypes at three studied loci were similar between the groups. However, the -43 SNP was significantly more frequent in T2DM patients with coexisting cardiovascular disease (CVD) than in patients without CVD (p=0.001). The -43 SNP was still significantly associated with the risk of CVD after adjusting for potential risk factors including male gender, age, BMI, dyslipidemia and hypertension. The odds ratio for G allele for CVD+ versus CVD- patients was 1.89, 95% CI 1.52-2.35. None of the studied SNPs was significantly associated with microvascular diabetic complications. There was a tendency to increased frequency of SNP -43 1/1 homozygotes in patients with diabetic retinopathy (p=0.057). The homozygous haplotype combination 121/121 was more frequent in T2DM patients than in non-diabetic controls (18.4% vs 10.5%, p=0.019). In conclusion, the results of our study suggest the significant association of SNP -43 with the risk of CVD coexisting with T2DM. We also observed that 121/121 haplotype was associated with T2DM in the studied population.

Transcription factor 7-like 2 (TCF7L2) gene polymorphism and complication/comorbidity profile in type 2 diabetes patients.

Transcription factor 7-like 2 gene (TCF7L2) has been associated with type 2 diabetes. We investigated the association of the rs7903146 SNP in this gene with clinical profile of type 2 diabetes (T2DM) patients. The study involved 980 patients with diabetic nephropathy (44%), diabetic retinopathy (42%), CVD (65%) and early onset of diabetes (45%) and 924 healthy controls. Subjects were genotyped for rs7903146 by PCR-RFLP. Genotype frequencies significantly differed between T2DM patients and controls (p<0.01, odds ratio (OR) for TT genotype 2.49 (95% confidence interval (CI) 1.84-3.39). An association was observed between rs7903146 and nephropathy (p<0.001), with 22% of TT homozygotes in this subgroup vs. 11% in patients without nephropathy (p=0.006, OR for TT 2.83, 95% CI 1.94-4.13). Association was stronger in patients with early onset of diabetes (34% of TT vs. 12% in the late onset, p<0.001). In DN group 71% of TT homozygotes had an early onset (OR 7.64, 95% CI 4.98-11.73 vs. controls). Our results confirm association of rs7903146 in the TCF7L2 gene with increased risk of type 2 diabetes. The T allele is strongly associated with nephropathy, especially in early onset of diabetes.