title: Association of GALNT3 gene polymorphisms with bone mineral density in Chinese postmenopausal women: the Peking Vertebral Fracture study.
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.
authors.affiliation: 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.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xiran
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ning
authors.forename: Yu
authors.initials: Y
authors.lastname: Pei
authors.forename: Chunlin
authors.initials: C
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.forename: Shuli
authors.initials: S
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D020868:Gene Silencing; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008159:Lumbar Vertebrae / Q000293:injuries*; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D015663:Osteoporosis, Postmenopausal / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016103:Spinal Fractures / Q000235:genetics*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D000089703:Fibroblast Growth Factor-23; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human