Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density.

TitleAssociation between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density.
Publication TypeJournal Article
Year of Publication1998
AuthorsRosen, CJ, Kurland, ES, Vereault, D, Adler, RA, Rackoff, PJ, Craig, WY, Witte, S, Rogers, J, Bilezikian, JP
JournalJ Clin Endocrinol Metab
Volume83
Issue7
Pagination2286-90
Date Published1998 Jul
ISSN0021-972X
KeywordsAged, Alleles, Bone Density, Dinucleotide Repeats, Female, Gene Frequency, Genotype, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Phenotype, Polymorphism, Genetic
Abstract

We recently demonstrated that insulin growth factor-I (IGF-I) cosegregates with bone mineral density (BMD) in progenitor crosses of two inbred strains of mice. Additionally, we reported that men with idiopathic osteoporosis (IOM) have low serum IGF-I levels, which can be related to BMD and bone turnover. In this study, we considered the possibility that serum IGF-I levels are influenced by molecular genetic variation in the IGF-I structural gene, and that a polymorphic microsatellite (CA repeat) in this locus can be used as a genetic marker for such comparisons. We studied 171 men and women, classified according to the trial in which they were participating. First, in 25 Caucasian men with IOM we noted a very high frequency (64%) of homozygosity for the most common allele (192 bp) in a dinucleotide repeat 1 kb upstream from the transcription start site of the IGF-I gene. This compared with a frequency of only 32% in healthy populations (both men and women) (P < 0.004). Next, we determined that for 116 healthy Caucasian men and women the 192/192 genotype was associated with lower serum IGF-I levels than all other genotypes (192/192: 129 +/- 7 ng/mL vs. others: 154 +/- 7 ng/mL, P = 0.03). We also noted that subjects possessing one 194-bp allele exhibited serum IGF-I levels 25% higher than those homozygous for 192 bp (192/192), (P < 0.005) even after correction for age and sex. Similarly, for men with the 192/192 genotype, serum IGF-I concentrations were lower than any other genotype (145 +/- 10 ng/mL vs. 183 +/- 9 ng/ml P < 0.02). In conclusion, low serum IGF-I levels found in men with IOM are associated with homozygosity for a specific allele of the IGF-I microsatellite (192/192), and individual variation in serum IGF-I levels is influenced by genetic factors and may be specifically influenced by variation at the IGF-I structural locus. Further family and pedigree studies are needed to characterize the relationship of bone mass acquisition to the IGF-I genotype.

DOI10.1210/jcem.83.7.4964
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID9661596