Association of the calpain-10 gene with microvascular function

Abstract

Aims/hypothesis. 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. Methods. Skin maximum microvascular hyperaemia to local heating on the dorsum of the foot (30 min at 43°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. Results. 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. Conclusions/interpretation. 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. [Diabetologia (2002) 45:899-904]

Differences in the association between type 2 diabetes and impaired microvascular function among Europeans and African Caribbeans

“…Polymorphisms in the Calpain 10 gene on a region of chromosome 2q37 are associated with risk of developing type 2 diabetes [38]. The polymorphism that confers susceptibility to type 2 diabetes is associated with altered microvascular function [39]. Although the prevalence of this gene has not been studied in African Caribbeans to date, it is reasonable to expect that this or other similar genes may play a dual role in the high incidence of diabetes and attenuated microvascular function.…”

Linkage of Calpain 10 to Type 2 Diabetes

“…In contrast, Haddad et al (18) reported no association of CAPN10 variation with PCOS. Shore et al (19) …”

“…They reported a 1.8-fold difference in expression of calpain 10 depending on the allele found at a synonymous polymorphism at CAPN10 (UCSNP-48). The UCSNP-48 site is in strong linkage disequilibrium with one of the sites (19) included in the polymorphisms defining the haplotype combination that is high risk for type 2 diabetes in the original studies on Mexican Americans. Ongoing studies are focused on identifying the particular variation(s) affecting this expression phenotype.…”

Type 2 diabetes candidate gene CAPN10: First, but not last

“…An association with microvascular function has been published [8], as have two studies on human adipocyte metabolism, -adrenoreceptor function [9], and glucose uptake [10] in human adipocytes. Surprisingly, the latter study suggested that UCSNP-43 carriers of the "protective" A allele had a lower insulin-stimulated glucose uptake in adipocytes than carriers of the G/G "risk" genotype.…”