肿瘤坏死因子α的单核苷酸多态性与中国汉族人强直性脊柱炎的关联分析

Association between single nucleotide polymorphism in TNF-α gene and ankylosing spondylitis in Chinese Han population

目的 :在中国汉族强直性脊柱炎 (AS)患者中 ,检测 TNF- α基因中的单核苷酸多态性 (SNPs)。 方法 :在 1 0 7例 AS患者和 1 1 6名正常对照中 ,用直接测序法和实时动态荧光 PCR结合等位基因特异扩增 ,对 TNF- α基因中的 3个启动子上的 SNPs(- 1 0 31 T/ C,- 86 3C/ A,- 85 7C/ T)和 2个内含子上的 SNPs(内含子 1的 +1 2 3C/ T和内含子 3的 +5 1 A/ G)进行基因分型 ,分析单个位点的等位基因和基因型频率是否与 AS相关。用单倍型推测软件计算上述位点单倍体型频率的分布 ,分析这些单倍体型是否与 AS的发病有关。 结果 :在 AS患者中 ,TNF- α的 - 85 7T和 - 86 3A的等位基因频率及它们的基因型频率显著性地超过健康对照组 ,经 Bonferroni校正后仍为阳性。对启动子上 3个 SNPs位点的两两和 3个位点组合的单倍体型频率分析表明 ,其在 AS患者和对照组中也均存在极其显著的差异 (P<0 .0 1 )。在 3个位点推测的单倍体型中 ,AS患者增加最显著的是TNF- 1 0 31 T/- 86 3C/- 857T单倍体型。 结论 :TNF-α基因上 2个 SNPs及单倍体型与中国汉族

Objective:To examine the single nucleotide polymorphisms (SNPs) in TNF α gene in Chinese Han population with ankylosing spondylitis (AS). Methods: An correlation analysis was performed in a case control cohort of 107 AS cases and 116 controls. Three SNPs located in the promoter of TNF α gene (-1 031T/C -863C/A,-857C/T) and 2 SNPs in intron (IVS1 +123C/T and IVS3 +51A/G) were examined by direct sequencing and real time fluorescence PCR with allele specific amplification. Haplotype inference software programs were used to caculate haplotype frequencies, and the relationship between haplotypes and AS was studied. Results: The frequencies of allele T at position -857 and allele A at position -863 significantly increased in AS cases vs controls, so were their genotype frequencies. These differences remained significant after Bonferroni's correction. Significant differences in the overall distribution of haplotype frequencies based on 3 and 2 SNP markers were found between 2 groups, with the most significant increase in the frequency of TNF -1 031C/-863C/-857T haplotype based on 3 SNP markers in AS patients. Conclusion: Our data demonstrate that the AS is highly associated with -857C/T -863C/A SNPs, and the inferred haplotypes of TNF α gene in Chinese Han population.