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

Abstract

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.

Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients

“…This finding does not seem to be influenced either by rhGH replacement or by severity of GHD (no difference in GH peak at stimulation test) or by primary pituitary pathology (no higher prevalence of craniopharyngioma in the noncarrier group). Even though the relatively small number of patients in each group does not allow us to draw consistent conclusions on this topic, the result of a less favorable metabolic profile in noncarriers of the WT allele is in agreement with previous studies in far larger cohorts reporting a higher prevalence of type 2 diabetes and an increased risk of fat accumulation in this genotype (10,28).…”

Family-based association study of IGF1 microsatellites and height, weight, and body mass index

“…23 Another Netherlands (Amsterdam) study found that homozygous carriers of 5¢CA-19, 5¢CA-20 or 5¢CA-19/20 heterozygotes had significantly higher BMI than women with other genotypes, for one of two cohorts examined. 27 We did not investigate these allele groupings specifically, but, inconsistent with these results, grouping 5¢CA-19 and 20 alleles did not yield a significant association with weight or BMI when tested under a recessive model (data not shown). Our study may not, however, have been sufficiently powered to detect the small differences (3 kg) in weight found in the Rotterdam study (n¼2590 women).…”

Insulin VNTR and IGF-1 Promoter Region Polymorphisms Are Not Associated with Body Composition in Early Childhood: The Generation R Study

“…We have previously found an association of INS VNTR with a gestational duration but not with birth weight [4]. A common promoter region polymorphism of the IGF1 gene, which is associated with circulating IGF-1 levels, has been suggested to affect birth weight, adult height and the risk of type 2 diabetes [1,7,8,9,10,11]. We and others could not replicate an association between variants of the IGF1 promoter region and birth weight [1,12,13].…”

“…Both polymorphisms have also been suggested to be associated with various measures of body composition, such as body mass index (BMI), fat mass and waist circumference [1,3,5,11,14,15]. To our knowledge, no studies have examined the associations of these common polymorphisms with body composition in infancy and early childhood.…”