研究人員分析了312人的基因變異性，其中超過(guò)一半的人有髖關(guān)節(jié)的問(wèn)題,，并在10年內(nèi)曾進(jìn)行過(guò)髖關(guān)節(jié)取代外科手術(shù),。這些病人有一些共同的癥狀,，其中91人有人工關(guān)節(jié)無(wú)菌性松弛(aseptic loosening)的征兆，其它的71人則有深層感染(deep-seated infection)的問(wèn)題,。
獲取受測(cè)者的DNA樣本后,，觀察他們的基質(zhì)金屬蛋白酶 (matrix metalloproteinase 1，MMP1)的基因變異,，因?yàn)镸MP1主要能調(diào)控白細(xì)胞介素6 (interleukin 6)以及維他命D (vitamin D)的生合成,。其中MMP1能夠分解膠原蛋白(collagen)，這種蛋白在骨骼及軟骨組織含量很多,，interleukin 6則與骨骼代謝及體內(nèi)免疫反應(yīng)有關(guān),，維他命D的合成更是骨骼健康的重要指標(biāo)。而這些物質(zhì)與髖關(guān)節(jié)的健康與否有很大的關(guān)系,。
結(jié)果顯示：在interleukin 6基因并沒(méi)有顯著的差異性,，但有人工髖關(guān)節(jié)無(wú)菌松弛病人的MMP1基因，變異程度卻較正常組高出3倍,，另外,，骨骼較易溶解或具有深層感染的病人其維他命D接受器基因(Vit D receptor gene)的變異則高出兩倍。作者總結(jié)表示：若這項(xiàng)研究發(fā)現(xiàn)確實(shí)無(wú)誤,，也許就可以利用這些基因變異作為長(zhǎng)期篩檢的指標(biāo),，也能以此指標(biāo)進(jìn)行藥物設(shè)計(jì)作為髖關(guān)節(jié)病變的治療。此研究發(fā)表于近期的Annals of the Rheumatic Diseases期刊,。
(資料來(lái)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: [email protected] .
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
