Melanocortin-3 receptor gene variants in a Maori kindred with obesity and early onset type 2 diabetes

Diabetes Res Clin Pract. 2002 Oct;58(1):61-71. doi: 10.1016/s0168-8227(02)00126-2.

Abstract

Genetic studies suggest a diabetes susceptibility locus on human chromosome 20, near the melanocortin receptor-3 (MC3-R) gene. We examined the MC3-R as a candidate gene for type 2 diabetes in 12 members of a large Maori kindred with multiple affected members. The coding region of the MC3-R gene was sequenced for both diabetic and non-diabetic individuals. Two separate single base pair substitutions were found in the MC3-R coding sequence and these resulted in amino acid changes, Lysine6Threonine and Isoleucine81Valine. Neither of these MC3-R variants tracked with the presence of diabetes. Furthermore, the variant and wild type MC3-R showed similar functional coupling to adenylyl cyclase. A polymorphic marker (D20S32e) close to the human MC3-R (hMC3-R) coding sequence was investigated in a 60-member pedigree for association with diabetes and other metabolic parameters. There was an association between D20S32e genotype and fasting insulin (P=0.0085) and the insulin resistance index, HOMA-R (P=0.0042). An association was also found between genotype and HDL levels during oral glucose tolerance testing (P=0.0037). These associations were independent of BMI, age, gender and diabetes. Our data do not support a role for variations in the coding region of the hMC3-R in the development of type 2 diabetes in this Maori kindred, but suggest that a locus on chromosome 20 q, close to D20S32e, may contribute to both insulin secretion and action in the Maori kindred.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Mass Index
  • Cell Line
  • Chromosomes, Human, Pair 20
  • Cloning, Molecular
  • DNA Primers
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / physiopathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Glucose Tolerance Test
  • Humans
  • Middle Aged
  • New Zealand
  • Obesity*
  • Pedigree
  • Polymerase Chain Reaction
  • Receptor, Melanocortin, Type 3
  • Receptors, Corticotropin / genetics*
  • Transfection
  • White People*

Substances

  • Blood Glucose
  • DNA Primers
  • Receptor, Melanocortin, Type 3
  • Receptors, Corticotropin