研究人员分析了312人的基因变异性，其中超过一半的人有髋关节的问题，并在10年内曾进行过髋关节取代外科手术。这些病人有一些共同的症状，其中91人有人工关节无菌性松弛(aseptic loosening)的征兆，其它的71人则有深层感染(deep-seated infection)的问题。
获取受测者的DNA样本后，观察他们的基质金属蛋白酶 (matrix metalloproteinase 1，MMP1)的基因变异，因为MMP1主要能调控白细胞介素6 (interleukin 6)以及维他命D (vitamin D)的生合成。其中MMP1能够分解胶原蛋白(collagen)，这种蛋白在骨骼及软骨组织含量很多，interleukin 6则与骨骼代谢及体内免疫反应有关，维他命D的合成更是骨骼健康的重要指标。而这些物质与髋关节的健康与否有很大的关系。
结果显示：在interleukin 6基因并没有显著的差异性，但有人工髋关节无菌松弛病人的MMP1基因，变异程度却较正常组高出3倍，另外，骨骼较易溶解或具有深层感染的病人其维他命D接受器基因(Vit D receptor gene)的变异则高出两倍。作者总结表示：若这项研究发现确实无误，也许就可以利用这些基因变异作为长期筛检的指标，也能以此指标进行药物设计作为髋关节病变的治疗。此研究发表于近期的Annals of the Rheumatic Diseases期刊。
(资料来源 : Bio.com)
部分英文原文：
Ann Rheum Dis. Published Online First: 15 March 2007. doi:10.1136/ard.2006.062018
Copyright © 2007 BMJ Publishing Group Ltd & European League Against Rheumatism
Genetic susceptibility to total hip replacement failure- Preliminary study on the influence of matrix metalloproteinase-1, interleukin-6 and vitamin D receptor polymorphisms
M HA Malik 1*, F Jury 2, A Bayat 2, W ER Ollier 2 and P R Kay 3
1 Arrowe Park Hiospital, Wirral NHS Trust and The University of Manchester, United Kingdom
2 CIGMR, University of Manchester, United Kingdom
3 Wrightington Hospital, United Kingdom
* To whom correspondence should be addressed. E-mail: hammymalik@hotmail.com .
Accepted 2 December 2006
Abstract
Matrix metalloproteinase-1 (MMP1), interleukin-6 (IL-6) and vitamin D receptor (VDR) have been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection resulting in periprosthetic bone loss around loosened total hip replacements (THR). Individual responses to such stimuli may be dictated by genetic variation and we have studied the effect of single nucleotide polymorphisms (SNPs) within these candidate genes. We performed a case-control study of these genes for possible association with deep sepsis or aseptic loosening. All cases were Caucasian patients with osteoarthritis who had received a cemented Charnley THR and polyethylene acetabular cup. Cases consisted of 91 patients with early aseptic loosening and 71 patients with deep infection. Controls consisted of 150 THAs that were clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening. DNA samples from all individuals were genotyped using Taqman allelic discrimination. The C allele (p=0.001; OR=3.27; 95% CI 2.21-4.83) and C/C genotype (p=0.001) for the MMP-1 SNP were highly associated with aseptic failure. No such statistically significant relationships were found aseptic loosening and the MMP-2, MMP-4, IL-6 -174 or VDR-L SNPs. The T allele (p=0.007; OR=1.76; 95% CI 1.16 - 2.66) and T/T genotype (p=0.028) for VDR-T were statistically associated with osteolysis due to deep infection. No such other statistically significant relationship was found. Aseptic loosening and possibly deep infection of THR may be under genetic influence and SNP markers may serve as predictors of implant survival and aid pharmacogenomic prevention of THR failure.
Keywords: aseptic loosening, infection, polymorphism, total hip replacement
