[No authors listed]
BACKGROUND:To date, more than 150 candidate genes related to osteoporosis have been described, but osteoporosis has increasingly been considered a polygenic disease modulated by environmental factors. It is thought that osteoporosis predisposition, pathology, and treatment response depend on the interaction between different genes or between genes and environmental factors. OBJECTIVE:The aim of this study was to evaluate the relationship between the presence of single nucleotide polymorphisms (SNPs) in the estrogen metabolic pathway and the development of osteoporosis and to determine whether this relationship is monogenic or whether interactions between genes exist. MATERIALS AND METHODS:A multicentric study with 1980 postmenopausal Spanish women in five Spanish communities was conducted. The women completed a specific questionnaire that inquired about risk factors for osteoporosis. Data on participants' bone mineral density were obtained with dual-energy X-ray densitometers, and genetic data were obtained from frozen peripheral blood. RESULTS:The digenic protection combinations indicated involvement of the wild-type genotype (WT) of the 3'UTR marker for the CYP19A1 gene, the IVS4 marker of the same gene, and the BMP15 and FSHR genes. Among patients who carried two or more of the genotypes considered 'risky', the triple combination among markers of the ESR2 and NRIP1 genes with any of the two mutations of the analyzed markers of the BMP15 gene gave a mean T-score value of -2.32±0.91 (p = 0.02). CONCLUSION:Variants of the new candidate genes (NRIP and BMP15) can predispose patients to osteoporosis.
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