Genetic variations in TCF7L2 influence therapeutic response to sulfonylureas in Indian diabetics

Sulfonylureas are widely used to treat type 2 diabetes, with considerable inter-individual variation in the hypoglycaemic response to sulfonylureas. Genetic variants in the gene encoding for transcription factor-7-like 2 (TCF7L2) have been associated with type 2 diabetes. This study aimed to study the effect of variations in TCF7L2 on therapeutic response to sulfonylureas in Type 2 diabetes mellitus patients. The effect of TCF7L2 rs12255372, rs7903146 and rs4506565 genotypes on glycaemic response was observed in 250 diabetic patients treated with sulfonylureas and sulfonylureas along with metformin. The genotyping tests were done by allele-specific multiplex PCR. Glycated haemoglobin (HbA1c) levels were used as phenotypic marker. 60% of sulfonylurea users did not achieve a target HbA1c levels of ⩽6.5% (48 mmol/mol) (which denotes good control in diabetics). Genotype influenced response to sulfonylureas, with more treatment failure in the TT homozygotes in case of rs12255372 and rs4506565. The GG genotype at rs12255372 favourably influences treatment success with sulfonylurea therapy in patients with type 2 diabetes (p ⩽ 0.05). At rs12255372, 70.5% GT or TT genotype failed to achieve therapeutic target, an absolute difference of 19% compared to GG homozygotes. Our preliminary data show that genetic variation at rs12255372 has a direct correlation with therapeutic success with sulfonylureas in type 2 diabetes, hence paving the way for better treatment outcomes in diabetics.