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The exon 3 polymorphism of the growth hormone receptor is a severity-related factor for osteoporosis
Felipe Albuquerque Marques1, Túlio Cesar Lins, Ricardo Moreno Lima
1Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, SGAN 916, Asa Norte, Brasília, DF, 70790-160, Brazil, felipe.marques@catolica.edu.br.
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.
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