Variants in the sulphonylurea receptor gene: association of the exon 16-3tvariant with Type II diabetes mellitus in Dutch Caucasians

Aims/hypothesis. We have analysed to what extent two previously reported si ngle nucleotide polymorphisms in the sulphonylurea receptor gene (SUR1) are associated with Type II (non-insulin-dependent) diabetes mellitus in The N etherlands. Furthermore, we estimated haplotype frequencies in control and diabetic populations, including data extracted from three other studies. Methods. Subjects with Type II diabetes (n = 388) and normoglycaemic subjec ts (n = 336) were randomly selected from two population-based studies, the Hoorn and Rotterdam studies. DNA was typed for variants in exon 16 (-3-->t variant in the splice acceptor site) and exon 18 (Thr(759)Thr, ACC-->ACT). Results. The genotype frequencies in both populations were similar. We obse rved an association of the exon 16-3t variant with Type II diabetes (allele frequencies 0.41 % vs 0.45 % in NGT and Type II diabetes, respectively, p = 0.01). There was no association between Type II diabetes and the variant in exon 18 or the combination of both variants (p > 0.5). A strong linkage disequilibrium between the exon 16 and exon 18 variants was observed in the diabetic groups but not, or less pronounced, in the control groups from th e different studies. Haplotype estimation shows that several different risk haplotypes exist in different Caucasian populations. Conclusion/interpretation. The exon 16-3t allele of the SUR1 gene is associ ated with Type II diabetes in the Netherlands. Based on estimated haplotype frequencies in different Caucasian populations we conclude that multiple h aplotypes on the SUR1 gene seem to confer a risk for developing Type II dia betes in Caucasians.