Abstract
Aim:
To simultaneously investigate the contribution of the alpha 1 chain of collagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the variation of bone geometric parameters in both Caucasians and Chinese.
Methods:
Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chinese subjects from 400 nuclear families were genotyped at the AHSG-SacI, COL1A1-PCOL2 and Sp1 polymorphisms using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). 5 FN bone geometric parameters were calculated based on bone mineral density and bone area of femoral neck (FN) measured by dual energy X-ray absorptiometry. Population stratification, total family association, within-family association, and linkage tests were performed by the quantitative transmission disequilibrium test program.
Results:
The t-test showed the significant differences of all bone geometric phenotypes (except ED) between Caucasians and Chinese in the offspring using both unadjusted and adjusted (by age, height, weight, and gender) data. In Caucasians, we found significant within-family association results between the COL1A1-Sp1 polymorphism (rs1800012) and cross sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR) (P = 0.018, 0.002, 0.023, and 0.001, respectively); the COL1A1-Sp1 polymorphism also detected significant linkage with BR (P = 0.039). In the population of China, the within-family associations between the COL1A1-PCOL2 polymorphism (rs1 107946) and CT, BR were significant (P = 0.012 and 0.008, respectively). Furthermore, evidence of linkage were observed between the AHSG-SacI polymorphism (rs4918) and CT, BR (P = 0.042 and 0.014, respectively) in Caucasians, but not in Chinese.
Conclusion:
Our results suggest that the COL1A1 gene may have significantly association with bone geometry in both Caucasians and Chinese, and the AHSG gene may be linked to bone geometry in Caucasians, but not in Chinese. This study represents our first efforts on investigating the importance of the COL1A1 and AHSG genes on bone geometry in both Caucasians and Chinese.
Similar content being viewed by others
Article PDF
References
Reginster JY, Burlet N . Osteoporosis: a still increasing prevalence. Bone 2006; 38: S4–9.
Ammann P, Rizzoli R . Bone strength and its determinants. Osteoporos Int 2003; 14 Suppl 3: S13–8.
Bouxsein ML . Bone quality: where do we go from here? Osteoporos Int 2003; 14 Suppl 5: 118–27.
Pulkkinen P, Partanen J, Jalovaara P, Jamsa T . Combination of bone mineral density and upper femur geometry improves the prediction of hip fracture. Osteoporos Int 2004; 15: 274–80.
Looker AC, Beck TJ . Maternal history of osteoporosis and femur geometry. Calcif Tissue Int 2004; 75: 277–85.
Peacock M, Turner CH, Econs MJ, Foroud T . Genetics of osteoporosis. Endocr Rev 2002; 23: 303–26.
Gnudi S, Ripamonti C, Gualtieri G, Malavolta N . Geometry of proximal femur in the prediction of hip fracture in osteoporotic women. Br J Radiol 1999; 72: 729–33.
Gnudi S, Malavolta N, Testi D, Viceconti M . Differences in proximal femur geometry distinguish vertebral from femoral neck fractures in osteoporotic women. Br J Radiol 2004; 77: 219–23.
Malavolta N, Frigato M, Mule R, Ripamonti C . Femoral neck morphology differentiates femoral neck from vertebral or hip osteoporotic fracture. Reumatismo 2003; 55: 93–7. Italian.
Koller DL, Liu G, Econs MJ, Hui SL, Morin PA, Joslyn G, et al. Genome screen for quantitative trait loci underlying normal variation in femoral structure. J Bone Miner Res 2001; 16: 985–91.
Slemenda CW, Turner CH, Peacock M, Christian JC, Sorbel J, Hui SL, et al. The genetics of proximal femur geometry, distribution of bone mass and bone mineral density. Osteoporos Int 1996; 6: 178–82.
Kannus P, Parkkari J, Sievanen H, Heinonen A, Vuori I, Jarvinen M . Epidemiology of hip fractures. Bone 1996; 18: 57S–63S.
Ross PD, Norimatsu H, Davis JW, Yano K, Wasnich RD, Fujiwara S, et al. A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians. Am J Epidemiol 1991; 133: 801–9.
Lei SF, Chen Y, Xiong DH, Li LM, Deng HW, Yan L, et al. Ethnic difference in osteoporosis-related phenotypes and its potential underlying genetic determination. J Musculoskelet Neuronal Interact 2006; 6: 36–46.
Theobald TM, Cauley JA, Gluer CC, Bunker CH, Ukoli FA, Genant HK . Black-white differences in hip geometry. Study of Osteoporotic Fractures Research Group. Osteoporos Int 1998; 8: 61–7.
Mann V, Ralston SH . Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 2003; 32: 711–7.
Ralston SH, Uitterlinden AG, Brandi ML, Balcells S, Langdahl BL, Lips P, et al. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 2006; 3: e90.
Lei SF, Deng FY, Liu XH, Huang QR, Qin Y, Zhou Q, et al. Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity. J Bone Miner Metab 2003; 21: 34–42.
Garcia-Giralt N, Nogues X, Enjuanes A, Puig J, Mellibovsky L, Bay-Jensen A, et al. Two new single-nucleotide polymorphisms in the COL1A1 upstream regulatory region and their relationship to bone mineral density. J Bone Miner Res 2002; 17: 384–93.
Liu PY, Lu Y, Long JR, Xu FH, Shen H, Recker RR, et al. Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their interactive effect influence bone mineral density in Caucasians. Med Genet 2004; 41: 752–7.
Dickson IR, Poole AR, Veis A . Localisation of plasma alpha2HS glycoprotein in mineralising human bone. Nature 1975; 256: 430–2.
Jahnen-Dechent W, Schinke T, Trindl A, Muller-Esterl W, Sablitzky F, Kaiser S, et al. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem 1997; 272: 31496–503.
Malone JD, Teitelbaum SL, Griffin GL, Senior RM, Kahn AJ . Recruitment of osteoclast precursors by purified bone matrix constituents. J Cell Biol 1982; 92: 227–30.
Yang F, Schwartz Z, Swain LD, Lee CC, Bowman BH, Boyan BD . Alpha 2-HS-glycoprotein: expression in chondrocytes and augmentation of alkaline phosphatase and phospholipase A2 activity. Bone 1991; 12: 7–15.
Dickson IR, Gwilliam R, Arora M, Murphy S, Khaw KT, Phillips C, et al. Lumbar vertebral and femoral neck bone mineral density are higher in postmenopausal women with the alpha 2HS-glycoprotein 2 phenotype. Bone Miner 1994; 24: 181–8.
Zmuda JM, Eichner JE, Ferrell RE, Bauer DC, Kuller LH, Cauley JA, et al. Genetic variation in alpha 2HS-glycoprotein is related to calcaneal broadband ultrasound attenuation in older women. Calcif Tissue Int 1998; 63: 5–8.
Nelson DA, Pettifor JM, Barondess DA, Cody DD, Uusi-Rasi K, Beck TJ . Comparison of cross-sectional geometry of the proximal femur in white and black women from Detroit and Johannesburg. J Bone Miner Res 2004; 19: 560–5.
Yan L, Crabtree NJ, Reeve J, Zhou B, Dequeker J, Nijs J, et al. Does hip strength analysis explain the lower incidence of hip fracture in the People's Republic of China? Bone 2004; 34: 584–8.
Deng HW, Shen H, Xu FH, Deng HY, Conway T, Zhang HT, et al. Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. J Bone Miner Res 2002; 17: 678–86.
Duan Y, Beck TJ, Wang XF, Seeman E . Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res 2003; 18: 1766–74.
Beck TJ, Stone KL, Oreskovic TL, Hochberg MC, Nevitt MC, Genant HK, et al. Effects of current and discontinued estrogen replacement therapy on hip structural geometry: the study of osteoporotic fractures. J Bone Miner Res 2001; 16: 2103–10.
QTDT program [updataed by 2006 Jun, cited by 2006 Jul]. Available from: http://www.sph.umich.edu/csg/abecasis/QTDT/.
Wang XF, Duan Y, Beck TJ, Seeman E . Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone 2005; 36: 978–86.
Liu XH, Liu YJ, Jiang DK, Li YM, Li MX, Qin YJ, et al. No evidence for linkage and/or association of human alpha2-HS glycoprotein gene with bone mineral density variation in Chinese nuclear families. Calcif Tissue Int 2003; 73: 244–50.
Xiong DH, Shen H, Xiao P, Guo YF, Long JR, Zhao LJ, et al. Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis. J Bone Miner Res 2006; 21: 424–37.
Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107: 899–907.
Beck TJ, Looker AC, Ruff CB, Sievanen H, Wahner HW . Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey dual-energy X-ray absorptiometry data. J Bone Miner Res 2000; 15: 2297–304.
Osawa M, Umetsu K, Ohki T, Nagasawa T, Suzuki T, Takeichi S . Molecular evidence for human alpha 2-HS glycoprotein (AHSG) polymorphism. Hum Genet 1997; 99: 18–21.
Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH . Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 1996; 14: 203–5.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project partially supported by the Scientific Research Fund of Hu-nan Provincial Education Department (No 05B037, 04B039), and the National Natural Science Foundation of China (No 30600364, 30230210, 30470534). HWD was partially supported by NIH grants (No K01 AR02170-01A2, R01 GM60402 and 5R01 AR050496-02).
Rights and permissions
About this article
Cite this article
Jiang, H., Lei, Sf., Xiao, Sm. et al. Association and linkage analysis of COL1A1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families. Acta Pharmacol Sin 28, 375–381 (2007). https://doi.org/10.1111/j.1745-7254.2007.00522.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00522.x
Keywords
This article is cited by
-
A trans‐ethnic two‐stage polygenetic scoring analysis detects genetic correlation between osteoporosis and schizophrenia
Clinical and Translational Medicine (2020)