儿童特应性皮炎IL-18基因启动子多态性与相关性研究

目的 检测儿童特应性皮炎患者外周血DNA中IL-18基因第2外显子上游启动子1第137和第607位点多态性，探讨其与儿童特应性皮炎发病的相关性。方法 从82例重庆汉族儿童特应性皮炎患者及健康对照组100例的抗凝血中提取DNA，用序列特异性引物PCR扩增技术（PCR-SSP）及PCR产物直接测序法鉴定基因类型，对结果进行统计学分析处理。结果 IL-18基因第2外显子的第137位点核苷酸存在G、C二态性，可表现为GG纯合、CC纯合、GC杂合三种基因型；第607位点核苷酸存在C、A二态性，可表现为CC纯合、AA纯合、CA杂合三种基因型。IL-18-137G/C基因型分布在患者组和对照组间差异有统计学意义，患者组137C等位基因频率显著高于对照组（χ2 = 4.54，P = 0.033），137C等位基因在重度组中分布频率显著高于轻度组（χ2 = 3.93，P < 0.05）；IL-18-607位点等位基因频率在轻度、中度、重度组及对照组之间分布差异无统计学意义（P > 0.05）；IL-18-137G/C位点C等位基因在病例与对照组比较，优势比OR = 1.76，137G/C基因型的优势比OR = 2.33。结论 儿童IL-18基因第2外显子上游启动子1第137和第607位点存在单核苷酸多态性，IL-18-137G/C是特应性皮炎患儿的候选易感基因。

Relationship between interleukin-18 gene promoter polymorphism and atopic dermatitis in children

Objective To investigate the polymorphism at positions-137 and -607 in the upstream promoter 1 region of exon 2 of interleukin(IL)-18 gene in Han children with atopic dermatitis(AD)in Chongqing,China,as well as its correlation with the development of AD.Methods Blood samples were collected from 82 patients with atopic dermatitis and 100 healthy controls.DNA was extracted from the samples and subjected to test with PCR.The polymorphism of IL-18 gene at positions-137 and -607 in the upstream promoter 1 region was analyzed by polymerase chain reaction(PCR)-sequence specific primers(SSP)and gene sequencing.Genotype frequency was compared between the patients and controls.Resuits A G/C polymorphism(GG,GC and CC genotypes)was identified at position-137 in exon 2 of IL-18 gene,and a C/A polymorphism(CC.CA and AA genotypes)at position-607 of this gene.The frequency of genotype GC at position-137 was significantly higher in the patients than that in the controls(47% vs 27%,P＜0.05;odds ratio=2.33.95% confidence interval 1.26-4.33).Increased frequency of C allele was also noted at the position-137 in the patients compared with the controls(0.24 vs 0.15,P＜0.05;odds ratio=1.76,95% confidence interval 1.04.2.97).Patients with severe AD(SCORAD score＞50)were more likely to carry C allele at position-137 of IL-18 gene than those with mild AD(SCORAD＜20).There was no statistical difference in allele frequency at -607(C/A)among patients with mild,moderate,severe AD and the controls(P＞0.05).Conclusions There is a polymorphism at positions -137 and -607 in the upstream promoter 1 region of IL-18 exon 2.The GC genotype of IL-18 at position -137 may confer the susceptibility to AD in Han children in Chongqing.