Association with replication between estrogen‐related receptor γ (ESRRγ) Polymorphisms and bone phenotypes in women of European ancestry |
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| Authors: | Latifa Elfassihi Sylvie Giroux Alexandre Bureau Nathalie Laflamme David EC Cole François Rousseau |
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| Affiliation: | 1. Centre de Recherche de l'H?pital St‐Fran?ois d'Assise du Centre Hospitalier Universitaire de Québec, Quebec, Canada;2. Faculté de Médecine, Université Laval, Quebec, Canada;3. Direction de la surveillance de l'état de santé de la population, Direction générale de la santé publique, Ministère de la santé et des services sociaux, Quebec, Canada;4. Centre de recherche Université Laval Robert‐Giffard, Quebec, Canada;5. Department of Clinical Pathology, Sunnybrook Health Sciences Centre and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;6. Centre for the Development, Evaluation and Rational Implementation of New Diagnostic Tools in Medicine (CEDERINDT)/The CanGèneTest Research Consortium on Genetic Laboratory Services, Quebec, Canada |
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| Abstract: | Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen‐related receptor γ (ESRRγ) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRγ sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual‐energy X‐ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRγ in the determination of bone density in women. © 2010 American Society for Bone and Mineral Research |
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| Keywords: | SNP polymorphism association bone density QUS |
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