A polymorphism (D20S32e) close to the human melanocortin receptor 3 is associated with insulin resistance but not the metabolic syndrome

Abstract

Insulin resistance (IR) is postulated to underlie diabetes, the metabolic syndrome (MS) and cardiovascular disease (CVD). The D20S32e marker close to the melanocortin receptor-3 ( hMC3-R) has been shown to be associated with IR in a large New Zealand Māori kindred, a population at high risk for MS and CVD. Here we examine the potential association of the D20S32e marker with the MS in this 60 member Māori kindred. There was a significant association between the D20S32e “B” allele and the fasting insulin component under both polygenic ( β = −5.3077; p = 0.008) and common sibship effect ( β = −4.2161; p = 0.03) models. No significant association between the same allele of D20S32e and the MS was observed after adjusting for age under a polygenic ( p = 0.103) or sibling ( p = 0.09) correlation model. We conclude that in this Māori kindred, the D20S32e polymorphism is significantly associated with insulin resistance but not with MS. Our data supports the hypothesis that multiple gene variants are necessary for the development of the MS.