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Menopause:
doi: 10.1097/GME.0b013e3182a34981
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Association of GALNT3 gene polymorphisms with bone mineral density in Chinese postmenopausal women: the Peking Vertebral Fracture study

Li, Nan MD; Wang, Xiran MD; Jiang, Yan MD; Wang, Wenbo MD; Huang, Wei MD; Zheng, Xin MD; Wang, Qiuping MD; Ning, Zhiwei MD; Pei, Yu MD; Li, Chunlin MD; Nie, Min MD; Li, Mei MD; Wang, Ou MD; Xing, Xiaoping MD; He, Shuli MD; Yu, Wei MD; Lin, Qiang MD; Xu, Ling MD; Xia, Weibo MD

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Abstract

Objective: GALNT3 gene encodes the glycosyltransferase polypeptide N-acetylgalactosaminyltransferase-3 (ppGalNacT3), which initiates the O-glycosylation of fibroblast growth factor 23 (FGF23) that is important in phosphorous regulation. Inactivating mutations of the GALNT3 gene can cause familial tumoral calcinosis. The aim of present study is to investigate the association of GALNT3 polymorphisms with osteoporosis phenotypes in Chinese postmenopausal women.

Methods: A community-based population of 1,353 postmenopausal women was randomly selected in Beijing. Bone mineral densities (BMDs) of the lumbar spine, femoral neck (FN), and total hip (TH) were measured by dual-energy x-ray absorptiometry. Vertebral fracture phenotypes were ascertained by vertebral x-ray reading. Osteoporotic fracture phenotypes were obtained from questionnaires. Single nucleotide polymorphisms of GALNT3 were determined by TaqMan allelic discrimination assay. Differences in BMD, serum phosphorus, or serum calcium across diverse genotypes or haplotypes were analyzed by general linear model analysis of covariance. Linear regression or logistic regression was used for association analyses of different osteoporosis phenotypes, phosphorous, or calcium. Partial correlation was used to investigate the relationship between phosphorus or calcium and BMD.

Results: We found that polymorphisms of rs1863196, rs6710518, and rs13429321 were significantly associated with FN BMD (P values of 0.002, 0.003, and 0.002, respectively). Polymorphisms of rs1863196, rs6710518, rs4667492, rs13429321, and rs6721582 were associated with TH BMD (P values of 0.002, 0.004, 0.037, 0.005, and 0.014, respectively). Haplotype-1 additive and dominant models were found to be associated with TH BMD (P values of 0.035 and 0.024, respectively). Haplotype-2 dominant model was found to be associated with FN BMD (P = 0.003) and TH BMD (P = 0.001).

Conclusions: GALNT3 may play a role in genetic susceptibility to osteoporosis among Chinese postmenopausal women. Efforts should be exerted to replicate our findings in other similar and ethnically diverse populations.

(C) 2014 by The North American Menopause Society.

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