Duymaz-Tozkir Jülide, Yilmaz Vuslat, Uyar F Aytül, Hajeer Ali H, Saruhan-Direskeneli Güher, Gül Ahmet
Department of Immunology, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey.
J Rheumatol. 2005 Jan;32(1):93-7.
Genetic susceptibility to Behçet's disease (BD) is well documented for HLA-B51; however, contribution of other genetic polymorphisms is estimated to be substantial. Interleukin 8 (IL-8), a potent chemoattractant for neutrophils, has been found to be elevated in BD serum, and the serum concentrations correlate with disease activity. Novel polymorphisms in IL-8 (CXCL8) and in one of its receptors, CXCR2 gene, may have a role in enhanced IL-8 activity in BD.
Three single nucleotide polymorphisms (SNP; -353 A/G, +1530 T/C, +3331 A/G) of the IL-8 gene and 2 SNP (+785 C/T and +1208 T/C) of the CXCR2 gene were screened in 100 patients with BD (61 men, 39 women, mean age 42.1 yrs) and 100 healthy controls (50 men, 50 women, mean age 36.8 yrs) by genotyping with PCR-RFLP and PCR-SSP methods.
No differences were observed between BD patients and controls for the allele and genotype frequencies of the screened IL-8 and CXCR2 gene polymorphisms. Distribution of these polymorphisms revealed no significant differences between clinical subgroups of BD patients. Each pair of the SNP -353/+1530, -353/+3331, and +1530/+3331 of IL-8 and +785/+1208 of CXCR2 showed strong linkage disequilibrium in both patients and controls (p < 0.001 for all). The distribution of the estimated IL-8 and CXCR2 haplotypes revealed no association with BD or any of its clinical subsets.
These results suggest that the IL-8 gene -353 A/G, +1530 T/C, and +3331 A/G and the CXCR2 gene +785 C/T and +1208 T/C polymorphisms have no role in the increased expression of IL-8 in BD.
HLA - B51对白塞病（BD）的遗传易感性已有充分记录；然而，据估计其他基因多态性的作用也很显著。白细胞介素8（IL - 8）是一种对中性粒细胞有强大趋化作用的物质，已发现其在BD患者血清中升高，且血清浓度与疾病活动度相关。IL - 8（CXCL8）及其受体之一CXCR2基因中的新型多态性可能在BD中增强IL - 8活性方面发挥作用。
采用PCR - RFLP和PCR - SSP方法对100例BD患者（61例男性，39例女性，平均年龄42.1岁）和100例健康对照者（50例男性，50例女性，平均年龄36.8岁）进行IL - 8基因的三个单核苷酸多态性（SNP；- 353 A/G、+ 1530 T/C、+ 3331 A/G）以及CXCR2基因的两个SNP（+ 785 C/T和+ 1208 T/C）的基因分型筛查。
在筛查的IL - 8和CXCR2基因多态性的等位基因和基因型频率方面，BD患者与对照者之间未观察到差异。这些多态性的分布在BD患者的临床亚组之间也未显示出显著差异。IL - 8的SNP - 353/+ 1530、- 353/+ 3331和+ 1530/+ 3331以及CXCR2的+ 785/+ 1208每对在患者和对照者中均显示出强连锁不平衡（所有p < 0.001）。估计的IL - 8和CXCR2单倍型分布与BD或其任何临床亚组均无关联。
这些结果表明，IL - 8基因的- 353 A/G、+ 1530 T/C和+ 3331 A/G以及CXCR2基因的+ 785 C/T和+ 1208 T/C多态性在BD中IL - 8表达增加方面不起作用。
