title: A haplotype of MATN3 is associated with vertebral fracture in Chinese postmenopausal women: Peking Vertebral Fracture (PK-VF) study.
abstract: The Matrilin3 gene (MATN3) encodes an extracellular matrix protein, which modulates chondrocyte differentiation. The aim of this study was to test for association of MATN3 polymorphisms with bone mineral density (BMD), fracture, vertebral fracture, bone turnover or 25-hydroxyvitamin D [25(OH)D] in postmenopausal women. A community-based population of 1488 postmenopausal women was randomly selected in Beijing. The history of fracture and vertebral fracture was obtained via questionnaire and vertebral X-ray respectively. BMD of lumbar spine (2-4), femoral neck and total hip were measured by dual energy X-ray absorptiometry. Serum N-terminal procollagen of type 1 collagen (P1NP), β-isomerized type I collagen C-telopeptide breakdown products (β-CTX) and 25(OH)D were quantified. Binary logistic regression revealed that Haplotype-4 was significantly associated with vertebral fracture risk in both additive model (p=0.023, OR=1.521) and dominant model (p=0.028, OR=1.623). The significance remained after 10,000 permutation tests to correct multiple testing (p=0.042). Re-selected age matched vertebral fracture case-control groups revealed similar associations in additive model (p=0.014, OR=1.927, 95%CI=1.142-3.253) and in dominant model (p=0.011, OR=2.231, 95%CI=1.200-4.148). However, no significant association was found between MATN3 polymorphisms and serum β-CTX, P1NP, 25(OH)D levels, or BMD. In linear regression, Haplotype-2 approached marginal significance in association with femoral neck BMD T-score (p=0.050), but this would account for only 0.2% of BMD variation in our sample. This study suggests that Haplotype-4 of MATN3 is associated with vertebral fracture risk independent of BMD in Chinese postmenopausal women. Efforts should be made to replicate our finding in other, similar and ethnically diverse, populations.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
authors.forename: Min
authors.initials: M
authors.lastname: Nie
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiran
authors.initials: X
authors.lastname: Wang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ning
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
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: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Lianmei
authors.initials: L
authors.lastname: Luo
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: Yu
authors.initials: Y
authors.lastname: Pei
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Youxia
authors.initials: Y
authors.lastname: Han
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Tong
authors.forename: Ying
authors.initials: Y
authors.lastname: Che
authors.forename: Ruixin
authors.initials: R
authors.lastname: Shen
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D024042:Collagen Type I / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D064235:Matrilin Proteins; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause / Q000235:genetics*; D011347:Procollagen / Q000378:metabolism; D016103:Spinal Fractures / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D064235:Matrilin Proteins; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D014807:Vitamin D; C104450:25-hydroxyvitamin D