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Author(s): Gaunt TR; Cooper JA; Miller GJ; Day INM; O'Dell SD
Title: Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males
Source: HUMAN MOLECULAR GENETICS 10 (14): 1491-1501
Date: 2001 JUL 1
Document Type: Journal : Article
Language: English
Comment:
Address: Univ Southampton, Sch Med, Human Genet Res Div, Southampton Gen Hosp, Southampton SO16 6YD, Hants, England.
Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, MRC,Epidemiol & Med Care Unit, Wolfson Inst Prevent Med, London EC1M 6BQ, England. Reprint: O'Dell, SD, Univ Southampton, Sch Med, Human Genet Res Div, Southampton
Gen Hosp, Duthie Bldg,MP 808,Tremona Rd, Southampton SO16 6YD, Hants, England. Abstract: 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 AIT in the IGF2 P1 promoter (P = 0.00012, n = 2394) and the newly identified SNPs 1156 CIT 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 Al T, and between ApaI and 1156 TIC, was minimal. Univariately 6815 AIT, 1156 TIC 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 AIT and 1156 TIC 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 AIT, 1156 TIC 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.
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