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The (GT) n polymorphism and haplotype of the COL1A2 gene, but not the (AAAG) n polymorphism of the PTHR1 gene, are associated with bone mineral density in Chinese

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Abstract

Collagen type I α2 (COL1A2) and parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR1) are two prominent candidate genes for bone mineral density (BMD). To test their importance for BMD variation in Chinese, we recruited 388 nuclear families composed of both parents and at least one healthy daughter with a total of 1,220 individuals, and simultaneously analyzed population stratification, total-family association, and within-family association between BMD at the spine and hip and the (GT) n marker in the intron 1 of the COL1A2 gene and the (AAAG) n marker in the P3 promoter of PTHR1 gene. We also performed these association analyses with haplotypes of the MspI and (GT) n polymorphisms in the COL1A2 gene. Significant within-family association was found between the M(GT) 12 haplotype and trochanter BMD (P<0.001). Individuals with this haplotype have, on average, 9.53% lower trochanter BMD than the non-carriers. Suggestive evidence of the within-family association was detected between the (GT) 17 allele and BMD at the spine (P=0.012), hip (P=0.011), femoral neck (P=0.032), trochanter (P=0.023), and intertrochanter (P=0.034). The association was confirmed by subsequent permutation tests. For the association, the proportion of phenotypic variance explained by the detected markers ranged from 1.2 to 3.9%, with the highest 3.9% at the trochanter for the M(GT) 12 haplotype. This association indicates that there is strong linkage disequilibrium between the polymorphisms (MspI and GT repeat polymorphism) in the COL1A2 gene and a nearby quantitative trait locus (QTL) underlying BMD variation in Chinese, or the markers themselves may have an important effect on the variation of BMD. On the other hand, no significant within-family association, population stratification and total-family association between the PTHR1 polymorphism and BMD were found in our Chinese population.

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Acknowledgements

The study was partially supported by a key project grant (30230210), an Outstanding Young Scientist Award (30025025), a general (30170504) from National Science Foundation of China (NSFC), a project from Scientific Research Fund of Hunan Provincial Education Department (02A027), and a Seed Fund (25000106) and a outstanding young award from Huo Ying Dong education foundation (81017). Investigators (H.-W.D., V.D.) were partially supported by grants from Health Future Foundation of USA, grants of National Health Institute (K01 AR02170-01, R01 GM60402-01A1), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program (LB595) and the State of Nebraska Tobacco Settlement Fund (LB692), and US department of Energy grant (DE-FG03-00ER63000/A00). We thank all the study subjects for volunteering to participate in the study. We thank Ms. Qi-Ren Huang, Ms. Yue-Juan Qin, and Ms. Qi Zhou from the Sixth Hospital of Shanghai, China, for coordinating sample recruitment.

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Authors and Affiliations

  1. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, Peoples’ Republic of China

    Shu-Feng Lei, Fei-Yan Deng, Man-Yuan Liu, Su-Mei Xiao, De-Ke Jiang & Hong-Wen Deng

  2. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, 601N. 30th St., Suite 6730, Omaha, NE, 68131, USA

    Volodymyr Dvornyk & Hong-Wen Deng

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  1. Shu-Feng Lei
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  2. Fei-Yan Deng
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  3. Volodymyr Dvornyk
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  4. Man-Yuan Liu
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  5. Su-Mei Xiao
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  6. De-Ke Jiang
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  7. Hong-Wen Deng
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Correspondence to Hong-Wen Deng.

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S.-F. Lei and F.-Y. Deng contributed equally to this work

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Lei, SF., Deng, FY., Dvornyk, V. et al. The (GT) n polymorphism and haplotype of the COL1A2 gene, but not the (AAAG) n polymorphism of the PTHR1 gene, are associated with bone mineral density in Chinese. Hum Genet 116, 200–207 (2005). https://doi.org/10.1007/s00439-004-1225-4

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  • DOI: https://doi.org/10.1007/s00439-004-1225-4

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