A polymorphic CA repeat in the IGF-I gene is associated with gender-specific differences in body height, but has no effect on the secular trend in body height.
Rietveld I., Janssen JA., van Rossum EF., Houwing-Duistermaat JJ., Rivadeneira F., Hofman A., Pols HA., van Duijn CM., Lamberts SW.
OBJECTIVE: A polymorphism near the promoter region of the IGF-I gene has been associated with serum IGF-I levels, age-related decline of serum IGF-I levels, body height, birth weight and intima media thickness in hypertensive subjects. DESIGN AND METHODS: We investigated the association between the length of the IGF-I alleles of this promoter polymorphism and IGF-I levels and body height. Furthermore, we investigated the potential influence of this polymorphism on final height in relationship to the secular trend of individuals born between 1917 and 1945. All subjects were participants of the Rotterdam Study. RESULTS: We observed, in analyses including only homozygous carriers, the highest IGF-I levels in homozygous carriers of the 192-bp allele (18.7 nmol/l +/- 0.6) and homozygous carriers of the 194-bp allele (17.7 nmol/l +/- 1.4). IGF-I levels were significantly lower in individuals with homozygous longer alleles [> 194-bp (12.0 nmol/l +/- 1.2; P < 0.001)] and homozygous shorter alleles [< 192-bp (15.6 nmol/l +/- 1.4; P < 0.05)] compared to homozygous carriers of the 192-bp and the 194-bp allele. In males and females separately, an optimum for serum IGF-I was also observed in homozygous carriers of the 192-bp and 194-bp allele. Only in males, homozygous carriers of the 192-bp allele were significantly taller than homozygous carriers of the shorter alleles (174.9 cm +/- 0.2 vs. 171.5 cm +/- 1.4; P = 0.01). When all subjects genotyped for the IGF-I promoter polymorphism were included in the analysis, a clear optimum for IGF-I levels and body height was observed in carriers of the 192-bp and/or 194-bp allele in the total population. Between 1917 and 1945, a secular trend in body height was observed in our Dutch population. Mean final body height was significantly higher in carriers of the most frequent alleles (192-bp and/or the 194-bp), than carriers of the remaining shorter and longer genotypes (P-trend < 0.01). CONCLUSIONS: In conclusion, we observed an optimum in IGF-I levels and final body height for the 192-bp and 194-bp allele of the IGF-I gene. A gender-specific effect of the IGF-I alleles on body height was observed. The secular trend in body height observed in our elderly Dutch population was similar for the different genotypes; carriers of the 192-bp and/or the 194-bp allele remained significantly taller throughout time.