Li Nan, Wang Xiran, Jiang Yan, Wang Wenbo, Huang Wei, Zheng Xin, Wang Qiuping, Ning Zhiwei, Pei Yu, Li Chunlin, Nie Min, Li Mei, Wang Ou, Xing Xiaoping, He Shuli, Yu Wei, Lin Qiang, Xu Ling, Xia Weibo
From the 1Department of Geriatric Endocrinology, Chinese PLA General Hospital, Beijing, China; 2Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China; 3Department of Cadre Unit, General Hospital of the Second Artillery Force, Beijing, China; 4Department of Endocrinology, Peking University Shougang Hospital, Beijing, China; 5Department of Endocrinology, Beijing Haidian Hospital, Beijing, China; 6Department of Endocrinology, China Rehabilitation Research Center, Beijing, China; 7Department of Endocrinology, Beijing Liangxiang Hospital, Beijing, China; 8Department of Endocrinology, Beijing Chaoyang Hospital, Beijing, China; and Departments of 9Radiology and 10Gynecology and Obstetrics, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
Menopause. 2014 May;21(5):515-21. doi: 10.1097/GME.0b013e3182a34981.
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.
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.
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).
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.
GALNT3基因编码糖基转移酶多肽N - 乙酰半乳糖胺基转移酶-3（ppGalNacT3），该酶启动成纤维细胞生长因子23（FGF23）的O - 糖基化，而FGF23在磷调节中起重要作用。GALNT3基因的失活突变可导致家族性肿瘤性钙化。本研究的目的是调查GALNT3基因多态性与中国绝经后女性骨质疏松症表型之间的关联。
在北京随机选取1353名社区绝经后女性。采用双能X线吸收法测量腰椎、股骨颈（FN）和全髋（TH）的骨密度（BMD）。通过脊柱X线阅片确定椎体骨折表型。骨质疏松性骨折表型通过问卷调查获得。采用TaqMan等位基因鉴别分析确定GALNT3的单核苷酸多态性。通过协方差的一般线性模型分析不同基因型或单倍型之间BMD、血清磷或血清钙的差异。采用线性回归或逻辑回归分析不同骨质疏松症表型、磷或钙之间的关联。采用偏相关分析研究磷或钙与BMD之间的关系。
我们发现rs1863196、rs6710518和rs13429321的多态性与FN BMD显著相关（P值分别为0.002、0.003和0.002）。rs1863196、rs6710518、rs4667492、rs13429321和rs6721582的多态性与TH BMD相关（P值分别为0.002、0.004、0.037、0.005和0.014）。发现单倍型-1加性和显性模型与TH BMD相关（P值分别为0.035和0.024）。发现单倍型-2显性模型与FN BMD（P = 0.003）和TH BMD（P = 0.001）相关。
GALNT3可能在中国绝经后女性骨质疏松症的遗传易感性中起作用。应努力在其他相似且种族多样的人群中重复我们的研究结果。
