强直性脊柱炎易感基因IL-1RN和TNF-α的单核苷酸多态性的研究

Single Nucleotide Polymorphism of IL-1RN and TNF-α in Ankylosing Spondylitis

目的检测中国深圳地区汉族强直性脊柱炎(AS)患者IL-1RN和TNF-α基因的单核苷酸多态性(SNPs)。方法在54名AS患者和42名健康对照者中,采用基因芯片技术对IL-1外显子6上SNPs(31017C/G、30735T/C)、TNF-α启动子上的SNPs(-857C/T)进行基因分型,分析单个位点的等位基因频率和基因型频率是否与AS相关,采用SAS软件分析数据。结果AS患者中,IL-1RN的31017C/G的等位基因G频率和30735T/C的等位基因C频率(分别是60.42%vs36.36%,32%vs17.19%)和IL-1RN的31017C/G的基因型GG频率和30735T/C的基因型CT频率(分别是43.75%vs12.12%,64%vs39.39%)显著性高于健康对照者,差异具有统计学意义(P<0.01)。TNF-α的-857C/T的等位基因T频率(25%vs9.52%)和基因型CT频率(42.59%vs19.05%)也显著高于健康对照者(P<0.01)。在健康人中31017CG/857CC基因型组合要显著高于AS患者(P<0.01),在AS患者中31017GG/30735CT/857CT基因型组合要显著高于健康对照者(P<0.05),其差异均具有统计学意义。结论IL-1RN基因的31017C/G和30735T/C的两个SNPs及其基因型频率与中国深圳汉族AS之间存在显著相关性,31017CG/857CC基因组合可能是保护性的基因组合,而31017GG/30735CT/857CT组合可能增加AS患病的易感性。

Objective To detect SNPs in the IL-1RN and TNF-α gene in ankylosing spondylities （AS）. Method 54 patients diagnosed with AS in accordance with 1984＇ diagnostic criteria and 42 health control subjects were included in this study. The gene polymorphism of IL-1RN31017 C/G、IL-1RN30735 T/C and TNF-α-857 T/C was analyzed. Result In the subjects with AS, the frequency of G allele in IL-1RN31017 C/G and C allele in 30735 T/C was higher than the healthy control subjects （60.42% vs 36.36%,32 % vs 17.19% respectively, P 〈 0.01）. The frequency of GG allele in IL-1RN31017 （43.75% vs 12.12% in control） and the frequency of CT allele in IL- 1RN30375 （64% vs 39.39% in control） was significantly higher than the control subjects （P 〈 0.01 ）. The frequency of the T at SNP position -857 and the phenotype -857CT frequency was also significantly increased in AS （25% vs 9.52% and 42.59% vs 19.05% respectively, P 〈 0.01 ）. To compare the genotypic combination with the non-genotypic combination, the frequency of the 31017CG/857CC genotypic combination in healthy controls was higher than AS （P 〈 0.01）. The frequency of the 31017GG/30735CT/857CT genotypic combination in AS was higher than the healthy control subjects （P 〈 0.05）. Conclusion There is a significant correlation between AS and the SNPs of IL-1RN 31017C/G and 30735 T/C. The occurrence of these genotypes is apparent in the Chinese Han population. Individuals with the 31017GG/30735CT/857CT genotypic combination are at high risk with AS.