Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males

Hum Mol Genet. 2001 Jul 1;10(14):1491-501. doi: 10.1093/hmg/10.14.1491.


We previously demonstrated an association between the insulin-like growth factor 2 (IGF2) gene 3'-untranslated region (3'-UTR) ApaI polymorphism and body mass index (BMI) in over 2500 middle-aged Caucasoid males. In the same cohort, we have now tested association with 11 more markers, including seven novel single nucleotide polymorphisms (SNPs), spanning >30 kb across the IGF2 gene. Three SNPs showed significant positive associations with BMI: 6815 A/T in the IGF2 P1 promoter (P = 0.00012, n = 2394) and the newly identified SNPs 1156 C/T in intron 2 (P = 0.017, n = 1567) and 1926 C/G in the 3'-UTR (P = 0.0062, n = 1872). There was strong pairwise linkage disequilibrium (LD) between the ApaI and 1926 C/G sites, whereas LD between ApaI and 6815 A/T, and between ApaI and 1156 T/C, was minimal. Univariately 6815 A/T, 1156 T/C and ApaI explained 1.03, 1.02 and 0.67% of the variation in BMI. Multi-way analysis of variance (ANOVA) models showed that 6815 A/T and 1156 T/C explained a further 0.4 and 0.8% of the variation beyond that accounted for by ApaI and the association of 1926 C/G with BMI disappeared after adjustment. The 6815 A/T, 1156 T/C and ApaI markers in effect constitute independent affirmations of our original hypothesized candidate gene region. In a stepwise multi-way ANOVA model, all three terms were significantly independently associated with BMI. The total proportion of BMI variance explained by this model was 2.25%, strongly suggesting that IGF2 genetic variation is a significant determinant of body weight in middle-aged males.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Biomarkers / analysis*
  • Body Mass Index*
  • Cohort Studies
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Gene Amplification
  • Genotype
  • Humans
  • Insulin / genetics*
  • Insulin-Like Growth Factor II / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Sequence Alignment


  • 3' Untranslated Regions
  • Biomarkers
  • Insulin
  • Insulin-Like Growth Factor II
  • Deoxyribonucleases, Type II Site-Specific