A haplotype of MATN3 is associated with vertebral fracture in Chinese postmenopausal women: Peking Vertebral Fracture (PK-VF) study.
A haplotype of MATN3 is associated with vertebral fracture in Chinese postmenopausal women: Peking Vertebral Fracture (PK-VF) study.
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作者：
Zhao J;Xia W;Nie M;Zheng X;Wang Q;Wang X;Wang W;Ning Z;Huang W;Jiang Y;Li M;Wang O;Xing X;Sun Y;Luo L;He S;Yu W;Lin Q;Pei Y;Zhang F;Han Y;Tong Y;Che Y;Shen R;Hu Y;Zhou X;Chen Q;Xu L
Matrilin3基因(MATN3)编码一种细胞外基质蛋白，调节软骨细胞的分化。本研究的目的是测试MATN3基因多态性与绝经后妇女骨密度(BMD)、骨折、椎体骨折、骨转换或25-羟基维生素D[25(OH)D]的相关性。在北京随机抽取了1488名绝经后妇女作为社区调查对象。分别通过问卷调查和椎体X线片获得骨折病史和椎体骨折史。采用双能X线骨密度仪测定腰椎(2~4)、股骨颈和全髋部骨密度。测定血清I型胶原N端前胶原(P1NP)、β异构化的I型胶原C端肽降解产物(β-CTX)和25(OH)D的含量。二项Logistic回归分析显示，在加性模型(p=0.023，OR=1.521)和显性模型(p=0.028，OR=1.623)中，单倍型4与椎体骨折风险显著相关。在10,000次排列测试以纠正多次测试(p=0.042)之后，这一重要性仍然存在。重新选择的年龄匹配的脊柱骨折病例对照组在加性模型(p=0.014，OR=1.927，95%CI=1.142-3.253)和显性模型(p=0.011，OR=2.231，95%CI=1.200-4.148)中显示出类似的相关性。然而，未发现MATN3基因多态与血清β-CTX、P1NP、25(OH)D水平或骨密度显著相关。在线性回归中，单倍型-2与股骨颈骨密度T评分的相关性接近边际意义(p=0.050)，但在我们的样本中，这只解释了骨密度变异的0.2%。这项研究表明，在中国绝经后妇女中，MATN3单倍型-4与椎体骨折风险无关，与骨密度无关。应该努力将我们的发现复制到其他类似和种族多样化的人群中。
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.
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