title: Assessment of linkage and association of 13 genetic loci with bone mineral density.
abstract: Bone mineral density (BMD), an important risk factor for osteoporosis, is a complex trait likely affected by multiple genes. The linkage and/or association of 13 polymorphic loci of seven candidate genes (estrogen receptor alpha [ERalpha] and beta [ERbeta], calcium-sensing receptor, vitamin D receptor, collagen type 1alpha1, low-density lipoprotein [LDL] receptor-related protein 5 [LRPS], and transforming growth factor beta1) were evaluated in 177 southern Chinese pedigrees of 674 subjects, with each pedigree identified through a proband having a BMD Z score of -1.28 or less at the hip or spine. A suggestive linkage was detected between the IVS1-351A/G polymorphism of ERalpha and spine BMD, and between the 1082G/A, 1730G/A, and D14S1026 polymorphisms of ERbeta and BMD at both spine and hip. The quantitative transmission disequilibrium test (QTDT) detected total family association between 1730G/A of ERbeta and BMD at spine and hip; between D14S1026 of ERbeta and hip BMD; and between the 266A/G and 2220C/T polymorphisms of LRP5 and hip BMD. Similar total family associations were detected when only the females were analyzed. In addition, the IVS1-397T/C polymorphism of ERalpha was associated with spine BMD, and the 266A/G and 2220C/T polymorphisms of LRP5 were associated with femoral neck BMD in the females. A within-family association was detected with the IVS1-397T/C polymorphism of ERalpha, and the 266A/G and 2220C/T polymorphisms of LRP5 in the females. The effect of each polymorphism on BMD variance ranged from 1% to 4%. In conclusion, ERalpha, ERbeta and LRP5 are important candidate genes determining BMD variation, especially in females.
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
authors.forename: Helen H L
authors.initials: HH
authors.lastname: Lau
authors.forename: Mandy Y M
authors.initials: MY
authors.lastname: Ng
authors.forename: William M W
authors.initials: WM
authors.lastname: Cheung
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.forename: Keith D K
authors.initials: KD
authors.lastname: Luk
authors.forename: Vivian
authors.initials: V
authors.lastname: Chan
authors.forename: Annie W C
authors.initials: AW
authors.lastname: Kung
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: C095550:CASR protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D016212:Transforming Growth Factor beta