Journal Article

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

Tom R. Gaunt, Jacqueline A. Cooper, George J. Miller, Ian N.M. Day and Sandra D. O’Dell

in Human Molecular Genetics

Volume 10, issue 14, pages 1491-1501
Published in print July 2001 | ISSN: 0964-6906
Published online July 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.14.1491
Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males

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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.

Journal Article.  9068 words.  Illustrated.

Subjects: Genetics and Genomics

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