IGF2BP2 gene variants influence repaglinide efficacy for treating Type 2 diabetes
MedWire News: Study results show that risk alleles of two variants of the insulin-like growth factor 2 mRNA-binding protein 2 gene (IGF2BP2) are present at a higher frequency and reduce the efficacy of repaglinide therapy in Chinese patients with Type 2 diabetes.
Zhao-qian Liu (Central South University, Changsha, China) and colleagues investigated whether risk alleles of two variants of IGF2BP2 – rs1470579 and rs4402960 – are associated with increased prevalence of Type 2 diabetes by genotyping 350 Chinese patients with Type 2 diabetes and 207 healthy controls.
Forty-two of the Type 2 diabetes patients were then randomly assigned to take repaglinide 3 mg/day for 8 weeks to determine if their IGF2BP2 genotype influenced the efficacy of the drug in reducing fasting and postprandial plasma glucose (F/PPG) levels.
As reported in the journal Acta Pharmacologica Sinica, frequencies of the risk-associated C allele of rs1470579 and T allele of rs4402960 were significantly higher in patients with Type 2 diabetes than controls, at 30.29% versus 24.64% and 27.14% versus 21.26%, respectively.
The team found that diabetics who were carriers of the C allele of rs1470579 had a significantly reduced repaglinide effect on FPG and PPG, with decreases of 1.19 and 2.84 mmol/l, respectively, over the 8 weeks compared with corresponding decreases of 2.55 and 5.26 mmol/l in A allele homozygotes with diabetes.
Conversely, repaglinide had an enhanced effect on postprandial serum insulin levels in Type 2 diabetics who were carriers of the T allele of rs4402960 compared with those who were GG homozygotes, with increases of 32.37 and 13.16 mU/l, respectively, over the 8 weeks.
The authors conclude that “variants in the IGF2BP2 gene are associated with Type 2 diabetes mellitus, and also associated with reduced therapeutic efficacy of repaglinide treatment.”
They add: “Understanding the biological mechanism by which variants in IGF2BP2 could mediate these effects on the biphasic pattern of insulin secretion will require further investigation.”
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By Helen Albert