Relations Between IGFBP-3 Promoter Polymorphism and Body Composition Parameters and Obesity

Park, Jong Suk; Chang, Yoon Soo; Yoo, Kyeong Nam; Nam, Joo Young; Kim, Chul Sik; Kim, Dol Mi; Cho, Min Ho; Park, Jina; Ahn, Chul Woo; Cha, Bong Soo; Lim, Sung Kil; Kim, Kyung Rae; Lee, Hyun Chul

Abstract

BACKGROUND: Insulin-like growth factor(IGF) binding protein-3(IGFBP-3), which binds to the IGFs in the circulation and acts as a main reservoir of them, regulates their biologic activities either in a IGF receptor dependent or independent manner. Circulating levels of IGF-1 and IGFBP-3 vary considerably among individuals and have been implicated in various medical conditions.
METHODS
Single nucleotide polymorphism at the-202 locus of the IGFBP-3 promoter, which influences transcriptional activities and is related with circulating IGFBP-3 levels, was genotyped for 262 samples from a study population who is older than 40 years.
RESULTS
The frequency of each polymorphic variation at the-202 locus in these study population was AA =115(43.9%), AC=125(47.7%), and CC=22(8.4%). In both genders, the subjects with the CC genotype were taller, whereas those with AC genotype had higher weight, BMI and BSA comparing those with the other genotypes, but these facts did not reach statistical significance. The prevalence of type 2 DM and the mean fasting blood glucose level did not differ among genotypes in the female gender. In the male population, however, the prevalence of type 2 DM was higher in the subjects with the AC genotype(p=0.016, chi-square-test), which is reflected by the elevated mean fasting glucose level (p=0.106, One-way ANOVA).
CONCLUSION
IGFBP-3 promoter-202 locus A/C polymorphism, which reflects its serum level and further implicates IGFs bioactivity, was associated with a higher prevalence of type 2 DM in the male gender. Although it did not reach statistical significance, the subjects with the CC genotype were the tallest among the genotypes and the subjects with the AC genotype had the highest BMI and weight, suggesting that IGFBP-3 might well play a role in body composition.