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Association between an IGF-I gene polymorphism and body fatness: differences between generations

Department of Pediatric Endocrinology, Canisius-Wilhelmina Hospital, PO Box 9015, 6500 GS Nijmegen, The Netherlands, ¹ Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, ² Institute for Research in Extramural Medicine, VU University Medical Centre, Amsterdam, The Netherlands and ³ Department of Pediatric Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands

(Correspondence should be addressed to P G Voorhoeve; Email: p.voorhoeve{at}cwz.nl)

Objective: A polymorphism near the promoter region of the IGF-I gene has been associated with serum IGF-I levels, body height and birth weight. In this study, we investigated whether this polymorphism is associated with body composition in young healthy subjects in two cohorts of different generations.

Design: Observational study with repeated measurements.

Methods: The study group consisted of two comparable young Dutch cohorts with a generational difference of around 20 years. The older cohort consisted of 359 subjects born between 1961 and 1965. Measurements were performed from 13 until 36 years of age. The younger cohort consisted of 258 subjects born between 1981 and 1989. Measurements were performed from 8 until 14 years of age. Height, body mass index (BMI), fat mass, fat-free mass, waist and hip circumference were compared between wild-type carriers and variant type carriers of the IGF-I polymorphism.

Results: In the younger cohort, body weight, BMI, fat mass and waist circumference were significantly higher in female variant carriers of the IGF-I polymorphism. A similar trend was observed in male variant carriers. In contrast, these differences were not observed in the older cohort. Irrespective of genotype, the younger cohort showed a significantly higher total fat mass, body weight and BMI compared with the older cohort.

Conclusions: Because the differences between both genotypes were small, it seems likely that the genetic variability due to this IGF-I polymorphism impacts only slightly on body composition. Importantly, our study suggested that associations between this IGF-I promoter polymorphism and body composition possibly reflect a gene–environmental interaction of this polymorphism and that an environment that promotes obesity leads to a slightly more pronounced fat accumulation in variant carriers of this IGF-I polymorphism.