A haplotype of MATN3 is associated with vertebral fracture in Chinese postmenopausal women: Peking Vertebral Fracture (PK-VF) study

Bone. 2012 Apr;50(4):917-24. doi: 10.1016/j.bone.2012.01.003. Epub 2012 Jan 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics*
  • Bone Density / genetics
  • Case-Control Studies
  • China
  • Collagen Type I / metabolism
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics*
  • Humans
  • Linkage Disequilibrium / genetics
  • Logistic Models
  • Matrilin Proteins
  • Middle Aged
  • Peptide Fragments / metabolism
  • Peptides / metabolism
  • Polymorphism, Single Nucleotide / genetics
  • Postmenopause / genetics*
  • Procollagen / metabolism
  • Spinal Fractures / genetics*
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism

Substances

  • Collagen Type I
  • Extracellular Matrix Proteins
  • Matrilin Proteins
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Vitamin D
  • 25-hydroxyvitamin D