Association Analyses of RANKL/RANK/OPG Gene Polymorphisms with Femoral Neck Compression Strength Index Variation in Caucasians

• Published in: Calcified tissue international Vol. 85; no. 2; pp. 104 - 112
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.08.2009; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Biochemistry; Biomedical and Life Sciences; Bone Density; Cell Biology; Compressive Strength; Endocrinology; Female; Femur Neck - diagnostic imaging; Femur Neck - physiology; Genetic Variation; Genotype & phenotype; Humans; Life Sciences; Male; Middle Aged; Neck; Orthopedics; Osteoporosis; Osteoprotegerin - genetics; Polymorphism; Polymorphism, Single Nucleotide; Radiography; RANK Ligand - genetics; Receptor Activator of Nuclear Factor-kappa B - genetics; Risk factors; United States; White People; United States; Femoral neck compression strength index; Femoral neck bone mineral density; gene; Femoral neck width; Quantitative transmission disequilibrium test
• ISSN: 0171-967X; 1432-0827; 1432-0827
• DOI: 10.1007/s00223-009-9255-5

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.