Investigation of MMP-1 genetic polymorphisms and protein expression and their effects on the risk of Kashin-Beck disease in the northwest Chinese Han population.

Zengtie Zhang,Feng Zhang,Aili Lv,Xiong Guo,Xiaowei Shi,Yan Wen,Jing Ma

doi:10.1186/s13018-016-0398-6

Abstract

BackgroundThe etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-1 (MMP-1) plays a central role in the initiation and progression of cartilage destruction; however, no study has reported on the relationship between KBD and MMP-1. This study was to investigate the role of MMP-1 in the pathogenesis and progression of KBD.MethodsSingle nucleotide polymorphism (SNP) genotyping was conducted for 274 KBD cases and 248 healthy controls using the Sequenom MassARRAY system. Additionally, the expression of MMP-1 in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry, and the concentration of MMP-1 in their joint fluid was also measured by enzyme-linked immunosorbent assay (ELISA).ResultsThe results showed that two SNPs (rs470221 and rs1144396) had a weak association with increased KBD risk; however, the significance of these results did not survive Bonferroni’s correction. Moreover, the percentages of cells expressing MMP-1 in each layer of cartilage were significantly higher in the KBD group than in the controls (F = 11.41–28.31, P = 0.002–0.000). The concentration of MMP-1 in KBD joint fluid was significantly higher than that in the controls (t = 9.83, P < 0.0001).ConclusionsThe increased expression of MMP-1 has a potential effect on the risk of KBD in the northwest Chinese Han population. However, six selected SNPs in the MMP-1 gene might not be useful as significant markers for predicting KBD susceptibility in Chinese Han population. Therefore, future studies in the association of MMP-1 with KBD should focus on other candidate SNPs.

Highlights

The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown
Single nucleotide polymorphism (SNP) selection and genotyping This study evaluated six single nucleotide polymorphisms (SNPs) of Matrix metalloproteinase-1 (MMP-1); we selected SNPs across the gene loci to ensure a high density of markers and to provide an adequate characterization of haplotype diversity
Baseline characteristics A total of 274 KBD patients and 248 age and sex matched controls were included in the genetic polymorphism study

Summary

Introduction

The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-1 (MMP-1) plays a central role in the initiation and progression of cartilage destruction; no study has reported on the relationship between KBD and MMP-1. This study was to investigate the role of MMP-1 in the pathogenesis and progression of KBD. Kashin-Beck disease (KBD) is a chronic osteochondropathy affecting the bones and joints that is endemic to certain geographical areas. A key pathological feature of KBD is chondrocyte necrosis in the deep zone of the growth plate of cartilage and articular cartilage [1, 2]. The disease usually presents in childhood, between 5 and 13 years of age, and mainly attacks the growth plate cartilage. KBD presents as dwarfism, very short upper limbs, and deformed and painful joints. Following cartilage damage, atrophied muscles occur due to joint pain and limited mobility; these deformed joints make manual farming work more difficult and painful

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