Human Molecular Genetics, 2001, Vol. 10, No. 14 1491-1501
© 2001 Oxford University Press
Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males
Human Genetics Research Division, University of Southampton School of Medicine, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton S016 6YD, UK and 1MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, St Bartholomew’s and The Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, Charterhouse Square, London EC1M 6BQ, UK
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.
+ To whom correspondence should be addressed. Tel: + 44 23 8079 6425; Fax: + 44 23 8079 4264; Email: S.D.O’Dell@soton.ac.uk
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