Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2

Am J Hum Genet. 2003 Aug;73(2):323-35. doi: 10.1086/377139. Epub 2003 Jul 8.

Abstract

We report a genomewide linkage study of type 2 diabetes (T2D [MIM 125853]) in the Icelandic population. A list of type 2 diabetics was cross-matched with a computerized genealogical database clustering 763 type 2 diabetics into 227 families. The diabetic patients and their relatives were genotyped with 906 microsatellite markers. A nonparametric multipoint linkage analysis yielded linkage to 5q34-q35.2 (LOD = 2.90, P=1.29 x 10(-4)) in all diabetics. Since obesity, here defined as body mass index (BMI) > or =30 kg/m(2), is a key risk factor for the development of T2D, we studied the data either independently of BMI or by stratifying the patient group as obese (BMI > or =30) or nonobese (BMI <30). A nonparametric multipoint linkage analysis yielded linkage to 5q34-q35.2 (LOD = 3.64, P=2.12 x (10)-5) in the nonobese diabetics. No linkage was observed in this region for the obese diabetics. Linkage analysis conditioning on maternal transmission to the nonobese diabetics resulted in a LOD score of 3.48 (P=3.12 x 10(-5)) in the same region, whereas conditioning on paternal transmission led to a substantial drop in the LOD score. Finally, we observed potential interactions between the 5q locus and two T2D susceptibility loci, previously mapped in other populations.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 5 / genetics*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genomic Imprinting
  • Humans
  • Iceland
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Obesity / complications
  • Obesity / pathology
  • Pedigree
  • Phenotype