Association of calpain-10 gene with microvascular function.

Abstract

Genotype could influence vascular function. In some populations, Calpain 10 gene polymorphisms increase susceptibility to diabetes or insulin resistance. Alterations in microvascular function could contribute to insulin resistance. This study investigated whether polymorphisms in the Calpain-10 gene influence microvascular function. Skin maximum microvascular hyperaemia to local heating on the dorsum of the foot (30 min at 43 degrees C) was measured by Laser Doppler Fluximetry in 37 healthy volunteers. All were normoglycaemic according to World Health Organisation criteria, normotensive and not on any medication. Four polymorphisms in the calpain-10 gene were typed: SNP-44, SNP-43, SNP-19, SNP-63. The SNP common to all the described high risk haplotypes is the G-allele at SNP-43. This intron 3 polymorphism appears to influence gene expression. Microvascular function was examined in relation to polymorphisms at this site alone as well as the effects of the known extended high risk haplotypes using the SNP's above. Maximum microvascular hyperaemia was increased in the 21 subjects with G/G genotypes at SNP-43 compared to the combined group of subjects ( G/ A genotype at SNP-43 ( n=12) + A/ A genotype at SNP-43 ( n=4)), and the minimum microvascular resistance was reduced 49.4 (39.6-94.2) vs 67.5 (39.1-107.3) mmHg/V, p=0.007). Haplotype analysis of the hyperaemic response revealed no significant differences between haplotypes. The two groups did not differ in terms of anthropometric measures, blood pressure, insulin resistance or glucose. The polymorphism that confers susceptibility to Type II (non-insulin-dependent) diabetes mellitus in some populations is associated in United Kingdom Caucasians with enhanced microvascular function in the presence of normoglycaemia.