Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population

Aims/hypothesis The gene encoding transcription factor 7-like 2 (TCF7L2) has been related to type 2 diabetes in multiple ethnic groups. Here, we investigate whether three single nucleotide polymorphisms (SNPs) in the TCF7L2 gene are associated with an impaired proinsulin:insulin ratio. Methods In this study we examined the associations between SNPs rs7901695, rs7903146 and rs12255372 in the TCF7L2 gene and metabolic variables affecting type 2 diabetes in a population-based study of 706 unrelated individuals (47% men and 53% women; aged 35-74 years) from the province of Segovia in central Spain (Castille), including 180 individuals with type 2 diabetes. Results The minor allele frequency of rs7901695, rs7903146 and rs12255372 was significantly higher in diabetic patients compared with that in non-diabetic individuals. The T (minor) allele of the variant rs7903146 was significantly associated with a greater OR for type 2 diabetes adjusted for age, sex and BMI in logistic regression analysis: OR 1.29 (95% CI 1.06-1.57, p=0.01). This risk allele was also associated with an increased proinsulin:insulin ratio after OGTT. Similar results were obtained for the other TCF7L2 SNPs. Conclusions/interpretation Our results provide further evidence supporting the belief that the TCF7L2 gene is a major determinant of type 2 diabetes risk in Spain, as in other southern European populations. The association with increased proinsulin:insulin ratio after an OGTT suggests that TCF7L2 might be involved in insulin synthesis and processing.