The exon 3 polymorphism of the growth hormone receptor is a severity-related factor for osteoporosis
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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.
KeywordsGrowth hormone receptor Polymorphism Growth Fat-free mass Bone mineral density Osteoporosis
This work was supported, in part, by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq:MCT/CNPq-02/2006-Universal-475438/2006-0), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and by the Fundação de Apoio à Pesquisa do Distrito Federal (FAP-DF).
All individuals, or their legal representatives, signed an informed consent allowing the use of their DNA for research purposes. The research protocol was approved by the Institutional Ethics Committee.
Conflict of interest
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