Hrycek Antoni, Siekiera Urszula, Cieślik Paweł, Szkróbka Witold
Department of Internal Diseases and Clinical Pharmacology, University School of Medicine, Katowice, Poland.
Rheumatol Int. 2005 Nov;26(1):1-6. doi: 10.1007/s00296-004-0503-8. Epub 2004 Sep 21.
The objective of this study was to evaluate the genetic profiles of selected cytokines (transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-6, interferon gamma, and interleukin-10) in systemic lupus erythematosus and the contributions of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles to susceptibility for this disease.
The study was carried out in 24 SLE patients and 36 healthy controls (from Upper Silesia) using polymerase chain reaction methods. All persons were of Caucasoid origin. Standard association analysis was used to compare the HLA alleles and frequency of cytokine gene polymorphisms between these groups.
Only the frequency of HLA-DRB107 allele was higher in SLE patients than controls (odds ratio 2.92, 95% confidence interval 1.16-7.33), but the difference did not reach statistical significance when Bonferroni's adjustment procedure was performed. No other significant associations were noted between class II alleles (DR1-DR6, DR8-DR10, DQ1-DQ4) and SLE. The frequency of the interleukin-6 GG and GC genotypes was significantly higher in SLE patients than in controls, and a significantly higher percentage of the G vs C alleles between patients and controls was revealed (odds ratio 2.53, 95% confidence interval 1.37-4.65, chi-squared test 8.16, P < 0.05). The most significant association of increased frequency of the G allele with SLE was more commonly noted in HLA-DRB107-positive patients (odds ratio 10.29, 95% confidence interval 5.34-19.83, P < 0.001). These data indicate that this combination could contribute toward determining the susceptibility to SLE, but its possible significance will require confirmation by further studies.
本研究的目的是评估系统性红斑狼疮中选定细胞因子(转化生长因子β1、肿瘤坏死因子α、白细胞介素-6、干扰素γ和白细胞介素-10)的基因谱,以及人类白细胞抗原(HLA)-DRB1和-DQB1等位基因对该病易感性的影响。
本研究使用聚合酶链反应方法对24例系统性红斑狼疮患者和36名健康对照者(来自上西里西亚)进行。所有受试者均为白种人。采用标准关联分析比较两组之间的HLA等位基因和细胞因子基因多态性频率。
仅系统性红斑狼疮患者中HLA-DRB107等位基因的频率高于对照组(优势比2.92,95%置信区间1.16-7.33),但在进行Bonferroni校正程序后,差异未达到统计学意义。在II类等位基因(DR1-DR6、DR8-DR10、DQ1-DQ4)与系统性红斑狼疮之间未发现其他显著关联。系统性红斑狼疮患者中白细胞介素-6 GG和GC基因型的频率显著高于对照组,且患者与对照组之间G等位基因与C等位基因的比例显著更高(优势比2.53,95%置信区间1.37-4.65,卡方检验8.16,P<0.05)。G等位基因频率增加与系统性红斑狼疮之间最显著的关联在HLA-DRB107阳性患者中更常见(优势比10.29,95%置信区间5.34-19.83,P<0.001)。这些数据表明,这种组合可能有助于确定系统性红斑狼疮的易感性,但其可能的意义需要进一步研究证实。