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Study of Association between Common Variation in the Insulin-Like Growth Factor 2 Gene and Indices of Obesity and Body Size in Middle-Aged Men and Women

Medical Research Council Epidemiology Unit (B.H., K.K.O., N.J.W., M.S.S.), Strangeways Research Laboratory, Cambridge CB1 8RN, United Kingdom; Institut National de la Santé et de la Recherche Médicale U780-IFR69 (B.H.), Faculté de Médecine Paris Sud, 94807 Villejuif, France; and Departments of Paediatrics (K.K.O.), and of Public Health and Primary Care (R.L., M.S.S.), Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, United Kingdom

Address all correspondence and requests for reprints to: Barbara Heude, Institut National de la Santé et de la Recherche Médicale U780, 16 Avenue Paul Vaillant Couturier, 94807 Villejuif cedex, France. E-mail: heude{at}vjf.inserm.fr.

Context: The IGF2 gene (IGF2) plays a key role in growth and is a candidate for association with obesity. Previous studies have reported that polymorphisms in IGF2 are associated with body weight and body mass index (BMI), but the results have been inconsistent.

Objectives: The aim of this study was primarily to confirm the association with BMI and, secondarily, to study the associations with other indices of body size.

Methods: In a sample of 2797 women and 2203 men aged 39–79 participating in the Norfolk arm of the European Prospective Investigation of Cancer, we genotyped three single nucleotide polymorphisms (SNPs) in the IGF2 gene that were previously associated with BMI [6815 A/T, 1156 T/C (G/A), and 820 G/A (ApaI)].

Results: No significant associations were observed between these SNPs and BMI. However, all three SNPs were significantly associated with height (P = 0.03 to 0.001). In a backward elimination regression analysis, two SNPs, 1156 T/C (G/A) and 820 G/A, remained independently associated with height (P = 0.003 and P = 0.038, respectively). Haplotype analysis of these two SNPs showed that carriers of the GA haplotype were shorter than carriers of each of the other three haplotypes (P < 0.001 for all comparisons).

Conclusions: We did not confirm the previously reported associations between IGF2 polymorphisms and BMI. However, our results suggest that common variation in the IGF2 gene may be associated with adult height. IGF2 could be considered as a candidate gene for future research on mechanisms for the association between height and chronic diseases, such as cancer, diabetes, and coronary heart disease.