Li Keshen, Yao Songpo, Liu Shengyuan, Wang Binyou, Mao Dongwei
Laboratory of Biochemistry and Molecular Biology, Harbin Engineering University, Harbin 150001, China.
Clin Chim Acta. 2009 Jul;405(1-2):30-4. doi: 10.1016/j.cca.2009.03.053. Epub 2009 Apr 5.
Interleukin-8 (IL-8), a CXC chemokine that recruits and activates inflammatory cells, plays a critical role in the pathogenesis of ulcerative colitis (UC). There are no studies on the association of single nucleotide polymorphisms (SNPs) of the IL-8 gene with the risk of UC.
All 162 unrelated UC patients and 203 control subjects were analyzed for 5 IL-8 SNPs ((-845 (T/C), -738 (T/A), -353 (A/T), -251 (T/A) and +678 (T/C)) using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and PCR-sequence-specific primers (SSP) method. Serum IL-8 concentrations were measured in all subjects.
Individual SNPs were not associated with risk for UC. However, the frequency of -353A/-251A/+678T haplotype was significantly higher in UC patients than in healthy controls (OR=1.454, p=0.036). By subgroup analyses, this haplotype tended to be more common in severe UC patients than in those with mild-to-moderate disease (OR=2.281, p=0.027). Furthermore, patients with AAT diplotype showed significantly increased serum IL-8 concentrations than those with other diplotypes (p<0.001).
These results suggest that IL-8 is a novel susceptibility gene to UC in Chinese UC patients, and furthermore, that IL-8 polymorphisms may be related to severe clinical subtype of UC.
白细胞介素-8(IL-8)是一种CXC趋化因子,可募集并激活炎症细胞,在溃疡性结肠炎(UC)的发病机制中起关键作用。目前尚无关于IL-8基因单核苷酸多态性(SNP)与UC风险关联的研究。
采用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)分析及PCR序列特异性引物(SSP)方法,对162例无血缘关系的UC患者和203例对照者进行5个IL-8 SNP((-845(T/C)、-738(T/A)、-353(A/T)、-251(T/A)和+678(T/C))分析。测定所有受试者血清IL-8浓度。
单个SNP与UC风险无关。然而,UC患者中-353A/-251A/+678T单倍型频率显著高于健康对照(OR=1.454,p=0.036)。通过亚组分析,该单倍型在重度UC患者中比轻度至中度疾病患者更常见(OR=2.281,p=0.027)。此外,AAT双倍型患者血清IL-8浓度显著高于其他双倍型患者(p<0.001)。
这些结果表明,IL-8是中国UC患者中UC的一个新的易感基因,此外,IL-8多态性可能与UC的严重临床亚型有关。