肿瘤坏死因子α基因多态性对强直性脊柱炎的易感性和临床表现型的影响

Influence of polymorphism in -238 and -308 sites of TNF-α promoter regions on susceptibility and phenotype of ankylosing spondylitis

目的 :探讨 TNF- α基因启动子 - 2 38和 - 30 8位点多态性对强直性脊柱炎 (AS)易感性和临床表现型的影响。方法 :采用 DNA直接测序法 ,对 1 0 8例 AS患者和 1 0 0名正常对照者 TNF- α- 2 38和 - 30 8位点进行基因分型 ,并分析基因型与疾病临床表现之间的关系。结果 :AS组 TNF-α - 2 38G/ G基因型有 1 0 6例 (98.1 % ) ,- 2 38G/ A基因型有 2例 (1 .9% ) ,正常对照组两种基因型分别有 95例 (95 .0 % )和 5例 (5 .0 % ) ,两组间比较无显著性差异 ;AS组 TNF-α - 30 8.1 .1 (G/ G)基因型有 89例 (82 .4 % ) ,- 30 8.1 .2 (G/ A)基因型有 1 9例 (1 7.6 % ) ,正常对照组中 - 30 8.1 .1 (G/ G)有 85例 (85 .0 % ) ,- 30 8.1 .2 (G/ A)有 1 4例 (1 4 .0 % ) ,- 30 8.2 .2 (A/ A)有 1例 (1 .0 % ) ,两组比较亦无显著性差异。 AS患者根据 X线判定的疾病严重程度在TNF-α - 30 8位点 G/ G、G/ A基因型之间有显著的不同 ,- 30 8.1 .2 (G/ A)基因型发病较轻 (P<0 .0 5 )。 结论 :在所研究的人群中未发现 TNF-α基因启动子 - 2 38和 - 30 8位点多态性与 AS的易感性相关 ,但 TNF-α基因启动子 - 30

Objective:To investigate the influence of polymorphism in the TNF α promoter regions on susceptibility and phenotype of ankylosing spondylitis(AS).Methods:Genomic DNA from 108 Chinese AS patients and 100 ethnically matched controls were genotyped for TNF α(-308G/A, -238G/A) polymorphism by direct sequencing.Correlation between genotype and clinical characteristics was statistically analyzed.Results:There were 106 patients (98.1%) with genotype -238G/G and 2 (1.9%) with -238G/A genotype in AS group; in healthy control group,the 2 genotypes were identified in 95 (95.0%) and 5 (5.0%) persons respectively.No significant difference in -238 genotype was found between the 2 groups.There were 89 patients (82.4%) with genotype -308.1.1(G/G) and 19(17.6%) with -308.1.2(G/A)genotype in AS group.In healthy control group,there were 85 persons (85.0%) with genotype -308.1.1(G/G),14(14.0%) with -308.1.2(G/A) and 1(1.0%) with -308.2.2(A/A).No significant difference was found neither between the 2 groups.However, significant difference( P <0.05) was found in the severities of AS between -308 G/G and G/A genotypes,with less severity in genotype -308.1.2(G/A). Conclusion:There is no association between the TNF α gene promoter polymorphism and AS,but it is suggested that the TNF α gene may play a role in the disease severity of the AS.