Association analyses of RANKL/RANK/OPG gene polymorphisms with femoral neck compression strength index variation in caucasians

Shan Shan Dong, Xiao Gang Liu, Yuan Chen, Yan Guo, Liang Wang, Jian Zhao, Dong Hai Xiong, Xiang Hong Xu, Robert R. Recker, Hong Wen Deng

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Femoral neck compression strength index (fCSI), a novel phenotypic parameter that integrates bone density, bone size, and body size, has significant potential to improve hip fracture risk assessment. The genetic factors underlying variations in fCSI, however, remain largely unknown. Given the important roles of the receptor activator of the nuclear factor-κB ligand/receptor activator of the nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) pathway in the regulation of bone remodeling, we tested the associations between RANKL/RANK/OPG polymorphisms and variations in fCSI as well as its components (femoral neck bone mineral density [fBMD], femoral neck width [FNW], and weight). This was accomplished with a sample comprising 1873 subjects from 405 Caucasian nuclear families. Of the 37 total SNPs studied in these three genes, 3 SNPs, namely, rs12585014, rs7988338, and rs2148073, of RANKL were significantly associated with fCSI (P = 0.0007, 0.0007, and 0.0005, respectively) after conservative Bonferroni correction. Moreover, the three SNPs were approximately in complete linkage disequilibrium. Haplotype-based association tests corroborated the single-SNP results since haplotype 1 of block 1 of the RANKL gene achieved an even more significant association with fCSI (P = 0.0003) than any of the individual SNPs. However, we did not detect any significant associations of these genes with fBMD, FNW, or weight. In summary, our findings suggest that the RANKL gene may play an important role in variation in fCSI, independent of fBMD and non-fBMD components.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalCalcified Tissue International
Volume85
Issue number2
DOIs
StatePublished - Aug 2009

Fingerprint

Femur Neck
Genes
Bone Density
Single Nucleotide Polymorphism
Cytoplasmic and Nuclear Receptors
Haplotypes
Osteoprotegerin
Weights and Measures
Bone Remodeling
Linkage Disequilibrium
Hip Fractures
Body Size
Nuclear Family
Neck
Ligands
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Association analyses of RANKL/RANK/OPG gene polymorphisms with femoral neck compression strength index variation in caucasians. / Dong, Shan Shan; Liu, Xiao Gang; Chen, Yuan; Guo, Yan; Wang, Liang; Zhao, Jian; Xiong, Dong Hai; Xu, Xiang Hong; Recker, Robert R.; Deng, Hong Wen.

In: Calcified Tissue International, Vol. 85, No. 2, 08.2009, p. 104-112.

Research output: Contribution to journalArticle

Dong, Shan Shan ; Liu, Xiao Gang ; Chen, Yuan ; Guo, Yan ; Wang, Liang ; Zhao, Jian ; Xiong, Dong Hai ; Xu, Xiang Hong ; Recker, Robert R. ; Deng, Hong Wen. / Association analyses of RANKL/RANK/OPG gene polymorphisms with femoral neck compression strength index variation in caucasians. In: Calcified Tissue International. 2009 ; Vol. 85, No. 2. pp. 104-112.
@article{abcf3405a88140dd9ec989c197b65982,
title = "Association analyses of RANKL/RANK/OPG gene polymorphisms with femoral neck compression strength index variation in caucasians",
abstract = "Femoral neck compression strength index (fCSI), a novel phenotypic parameter that integrates bone density, bone size, and body size, has significant potential to improve hip fracture risk assessment. The genetic factors underlying variations in fCSI, however, remain largely unknown. Given the important roles of the receptor activator of the nuclear factor-κB ligand/receptor activator of the nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) pathway in the regulation of bone remodeling, we tested the associations between RANKL/RANK/OPG polymorphisms and variations in fCSI as well as its components (femoral neck bone mineral density [fBMD], femoral neck width [FNW], and weight). This was accomplished with a sample comprising 1873 subjects from 405 Caucasian nuclear families. Of the 37 total SNPs studied in these three genes, 3 SNPs, namely, rs12585014, rs7988338, and rs2148073, of RANKL were significantly associated with fCSI (P = 0.0007, 0.0007, and 0.0005, respectively) after conservative Bonferroni correction. Moreover, the three SNPs were approximately in complete linkage disequilibrium. Haplotype-based association tests corroborated the single-SNP results since haplotype 1 of block 1 of the RANKL gene achieved an even more significant association with fCSI (P = 0.0003) than any of the individual SNPs. However, we did not detect any significant associations of these genes with fBMD, FNW, or weight. In summary, our findings suggest that the RANKL gene may play an important role in variation in fCSI, independent of fBMD and non-fBMD components.",
author = "Dong, {Shan Shan} and Liu, {Xiao Gang} and Yuan Chen and Yan Guo and Liang Wang and Jian Zhao and Xiong, {Dong Hai} and Xu, {Xiang Hong} and Recker, {Robert R.} and Deng, {Hong Wen}",
year = "2009",
month = "8",
doi = "10.1007/s00223-009-9255-5",
language = "English",
volume = "85",
pages = "104--112",
journal = "Calcified Tissue International",
issn = "0171-967X",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Association analyses of RANKL/RANK/OPG gene polymorphisms with femoral neck compression strength index variation in caucasians

AU - Dong, Shan Shan

AU - Liu, Xiao Gang

AU - Chen, Yuan

AU - Guo, Yan

AU - Wang, Liang

AU - Zhao, Jian

AU - Xiong, Dong Hai

AU - Xu, Xiang Hong

AU - Recker, Robert R.

AU - Deng, Hong Wen

PY - 2009/8

Y1 - 2009/8

N2 - Femoral neck compression strength index (fCSI), a novel phenotypic parameter that integrates bone density, bone size, and body size, has significant potential to improve hip fracture risk assessment. The genetic factors underlying variations in fCSI, however, remain largely unknown. Given the important roles of the receptor activator of the nuclear factor-κB ligand/receptor activator of the nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) pathway in the regulation of bone remodeling, we tested the associations between RANKL/RANK/OPG polymorphisms and variations in fCSI as well as its components (femoral neck bone mineral density [fBMD], femoral neck width [FNW], and weight). This was accomplished with a sample comprising 1873 subjects from 405 Caucasian nuclear families. Of the 37 total SNPs studied in these three genes, 3 SNPs, namely, rs12585014, rs7988338, and rs2148073, of RANKL were significantly associated with fCSI (P = 0.0007, 0.0007, and 0.0005, respectively) after conservative Bonferroni correction. Moreover, the three SNPs were approximately in complete linkage disequilibrium. Haplotype-based association tests corroborated the single-SNP results since haplotype 1 of block 1 of the RANKL gene achieved an even more significant association with fCSI (P = 0.0003) than any of the individual SNPs. However, we did not detect any significant associations of these genes with fBMD, FNW, or weight. In summary, our findings suggest that the RANKL gene may play an important role in variation in fCSI, independent of fBMD and non-fBMD components.

AB - Femoral neck compression strength index (fCSI), a novel phenotypic parameter that integrates bone density, bone size, and body size, has significant potential to improve hip fracture risk assessment. The genetic factors underlying variations in fCSI, however, remain largely unknown. Given the important roles of the receptor activator of the nuclear factor-κB ligand/receptor activator of the nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) pathway in the regulation of bone remodeling, we tested the associations between RANKL/RANK/OPG polymorphisms and variations in fCSI as well as its components (femoral neck bone mineral density [fBMD], femoral neck width [FNW], and weight). This was accomplished with a sample comprising 1873 subjects from 405 Caucasian nuclear families. Of the 37 total SNPs studied in these three genes, 3 SNPs, namely, rs12585014, rs7988338, and rs2148073, of RANKL were significantly associated with fCSI (P = 0.0007, 0.0007, and 0.0005, respectively) after conservative Bonferroni correction. Moreover, the three SNPs were approximately in complete linkage disequilibrium. Haplotype-based association tests corroborated the single-SNP results since haplotype 1 of block 1 of the RANKL gene achieved an even more significant association with fCSI (P = 0.0003) than any of the individual SNPs. However, we did not detect any significant associations of these genes with fBMD, FNW, or weight. In summary, our findings suggest that the RANKL gene may play an important role in variation in fCSI, independent of fBMD and non-fBMD components.

UR - http://www.scopus.com/inward/record.url?scp=69249215226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69249215226&partnerID=8YFLogxK

U2 - 10.1007/s00223-009-9255-5

DO - 10.1007/s00223-009-9255-5

M3 - Article

C2 - 19458885

AN - SCOPUS:69249215226

VL - 85

SP - 104

EP - 112

JO - Calcified Tissue International

JF - Calcified Tissue International

SN - 0171-967X

IS - 2

ER -