title: Association with replication between estrogen-related receptor gamma (ESRRgamma) polymorphisms and bone phenotypes in women of European ancestry.
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 gamma (ESRRgamma) 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 ESRRgamma 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 ESRRgamma in the determination of bone density in women.
authors.affiliation: Centre de Recherche de l'Hôpital St-François d'Assise du Centre Hospitalier Universitaire de Québec, Quebec, Canada.
authors.forename: Latifa
authors.initials: L
authors.lastname: Elfassihi
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giroux
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bureau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Laflamme
authors.forename: David Ec
authors.initials: DE
authors.lastname: Cole
authors.forename: François
authors.initials: F
authors.lastname: Rousseau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000473:pathology; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006365:Heel / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011792:Quebec / Q000453:epidemiology; D011960:Receptors, Estrogen / Q000235:genetics*; D014463:Ultrasonography
chemical_list: C490917:ESRRG protein, human; D011960:Receptors, Estrogen