Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study.
Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study.
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DOI：
10.1186/1471-2350-10-109
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发表时间：
2009-10-27
影响因子：
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通讯作者：
Petrek M
中科院分区：
文献类型：
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作者：
Gallo J;Mrazek F;Petrek M
全髋关节置换术（THA）生存率的差异可能受到个体对假体周围骨质溶解的易感性的影响。这可能是由参与THA中骨质溶解发展的细胞因子和细胞因子受体基因的功能多态性驱动的，从而对个体的表型产生影响。我们对11种细胞因子和2种细胞因子受体候选基因的22个单核苷酸多态性（SNP）与髋臼骨质溶解严重程度和THA失败风险的相关性进行了研究。研究了205例非骨水泥型THA（ABG 1）的无关白人患者的样本。通过单变量和多变量分析确定所研究的SNP变体在轻度和重度髋臼骨质溶解组之间的分布。通过考克斯风险模型分析时间依赖性输出变量。单变量分析显示：1）TNF-238*A等位基因与严重骨溶解相关（比值比，OR = 6.59，p = 0.005，人群归因风险，PAR 5.2%）; 2）IL 6 -174*G等位基因携带者发生严重骨质溶解的倾向是非携带者的2.5倍（3）IL 2 -330*G等位基因的携带与严重骨溶解的保护作用相关（OR = 0.55，p = 0.043）。基于逻辑回归，等位基因TNF-238*A和IL-6 -174*G是严重髋臼骨溶解发展的独立预测因子。根据考克斯模型，TNF-238*A携带者THA失败的累积风险增加（p = 0.024）。相反，IL 2 -330*G等位基因预测THA失败的累积风险较低（p = 0.019）。促炎性细胞因子TNF-α和IL-6的遗传变异赋予对严重OL的易感性。这样，次要TNF等位基因的存在可增加THA失败的累积风险。相反，IL 2基因的SNP可能保护携带者免于上述THA并发症。
The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype. We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model. Univariate analysis showed: 1) TNF-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p = 0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based on logistic regression, the alleles TNF-238*A and IL6-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of TNF-238*A had increased cumulative hazard of THA failure according to Cox model (p = 0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA failure (p = 0.019). Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor TNF allele could increase the cumulative risk of THA failure. Conversely, SNP in the IL2 gene may protect carriers from the above THA complications.