Novel polymorphisms in the GCKR gene and their influence on glucose and insulin levels in a Danish twin population

Aim The glucokinase regulatory protein gene is a candidate gene for Type 2 diabetes. This study reveals three new polymorphisms and examines the impact of one new and one known polymorphism on insulin secretion and parameters associated with the insulin resistance syndrome in Danish twins with different degrees of glucose tolerance. Methods Single nucleotide polymorphism detection was performed in 20 healthy subjects and in 20 subjects with Type 2 diabetes. The effect of the polymorphisms on lipid, glucose and insulin measures was studied in 566 same-sex twins aged 55-74 years. Results The new nucleotide (nt) 363 polymorphism was found only in subjects with impaired glucose tolerance and Type 2 diabetes. The nt 11216 polymorphism influenced insulin measured at 120 min during an oral glucose tolerance test (OGTT). Subjects with genotype C11216C/T11216C had 21% higher insulin values (P < 0.05) than subjects with genotype T11216T. In twins discordant for this genotype, the C-allele was associated with significantly higher plasma insulin levels at all time points during the OGTT, higher beta-cell function and lower plasma glucose levels during the OGTT. Conclusion The C-allele of nt 11216 polymorphism was associated with increased insulin secretion, and may therefore exert a potentially protective effect against Type 2 diabetes. This remains to be shown in a larger study population.