title: Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.
abstract: Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.
authors.affiliation: The First Department of Orthopedics, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Zhang's Orthopaedic Hospital, Taizhou, Zhejiang, China.
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Zhang's Orthopaedic Hospital, Taizhou, Zhejiang, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: The First Department of Orthopedics, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Division of Biology &Biomedical Sciences, Washington University in Saint Louis, MO, USA.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.|Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.|Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.|Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine &Forensics, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Dongke
authors.initials: D
authors.lastname: Fu
authors.affiliation: The First Department of Orthopedics, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: KunZheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015519:Bone Density; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D058574:Integrin-Binding Sialoprotein; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein