The exon 3 polymorphism of the growth hormone receptor is a severity-related factor for osteoporosis

Endocrine. 2014 Apr;45(3):487-96. doi: 10.1007/s12020-013-0004-1. Epub 2013 Jun 28.

Abstract

The purpose of this study was to investigate the association between the GHR exon 3 fl/d3 polymorphism and body composition traits in Brazilian cohorts of normal post-menarche adolescent girls and in post-menopausal women with and without osteoporosis. First, multiplex PCR and quantitative PCR (TaqMan) were used with 105 DNA samples from the general Brazilian population to validate the SNP rs6873545 as a surrogate marker for the GHR polymorphism. Subsequently, genotyping was carried out to evaluate associations for this polymorphism in 136 post-menarche adolescents and 175 post-menopausal women, who were evaluated for body composition traits such as bone mineral density and fat-free mass. Statistical analysis used an independent sample t test, one-way ANOVA test and post hoc Tukey HSD test. Significant values were assumed by p < 0.05. Genotyping indicated complete linkage disequilibrium between the GHR polymorphism and the SNP alleles (r(2) = 1.0). Adolescents and healthy post-menopausal women showed no genotype associations for body composition traits or osteoporosis. However, a lower total body bone mineral density was observed in fl/fl post-menopausal women with osteoporosis (p = 0.0004). These results suggest that the SNP rs6873545 can be used as a surrogate for the GHR fl/d3 polymorphism due to linkage disequilibrium in the Brazilian population and that the fl/fl genotype is a severity-related risk factor for osteoporosis, but did not appear to be associated with disease status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthropometry
  • Body Composition / genetics*
  • Body Composition / physiology
  • Bone Density / genetics*
  • Bone Density / physiology
  • Brazil / epidemiology
  • Carrier Proteins
  • Child
  • Exons / genetics
  • Female
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Menarche / physiology
  • Menopause / genetics
  • Middle Aged
  • Osteoporosis / epidemiology
  • Osteoporosis / genetics*
  • Polymorphism, Genetic / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Growth Factor / genetics*
  • Severity of Illness Index
  • Young Adult

Substances

  • Carrier Proteins
  • Receptors, Growth Factor
  • somatotropin-binding protein