我国广东地区汉族人群类风湿性关节炎患者IL-6启动子基因多态性的研究

Study on the gene polymorphism of interleukin-6 promoter in rheumatoid arthritis patients of Chinese Han population in the region of Guangdong

目的了解我国广东地区汉族人群白细胞介素-6（IL-6）基因启动子-572C/G和-174G/C位点单核苷酸多态性对类风湿性关节炎（RA）的影响。方法应用序列特异性引物-聚合酶链反应（PCR-SSP）检测168名体检健康者和120例RA患者的IL-6基因启动子-572和-174位点的基因型。结果我国广东地区汉族人群IL-6基因启动子-572位点存在C→G的突变,其基因型和等位基因频率分布在RA组和对照组比较差异有统计学意义（基因型频率：2χ=16.14,P=0.003;等位基因频率：2χ=16.71,P〈0.001）,其G等位基因在RA患者中明显低于健康对照组[比值比（OR）=0.36,95%可信区间（CI）：0.21-0.61];-174位点存在G→C的突变,其基因型和等位基因分布频率在两组间差异亦有统计学意义（基因型频率：2χ=25.75,P〈0.01;等位基因频率：2χ=25.99,P〈0.01）,其C等位基因在RA组明显高于健康对照组（OR=2.26,95%CI：1.91-2.68）。结论我国广东地区汉族人群IL-6基因启动子存在-572C/G与-174G/C的单核苷酸多态性,且这2个位点多态性与RA有关,其中IL-6-572位点的G等位基因可能对RA有保护作用,而IL-6-174位点等位基因C可能与RA发病的易感性有关。

Objective To investigate the two single-nucleotide polymorphisms（SNPs） located at positions -572 and - 174 in the promoter region of interleukin-6（ IL-6）, and disclose whether such polymorphisms are associated with susceptibility to rheumatoid arthritis（RA） in the Chinese HaM population of Guangdong province. Methods Using polymerase chain reaction with sequence specific primers（PCR-SSP） method, SNPs of the promoter region of IL-6 gene at position -572 and - 174 were detected in 120 patients with RA and 168 normal controls. Results There was statistically significant difference in frequencies of genotype and allele in - 572C/G of the promoter region of IL-6 between RA patients and the controls （ genotype ： X2 = 16. 14, P = 0. 003 ; allele： X2 = 16. 71, P 〈 0. 001 ）. The frequency of - 572 G allele in RA patients was significantly lower than that in normal controls（ odds ratio [ OR] =0.36, 95% confidence interval [ CI] ： 0.21-0.61 ）. There was significant difference with genotype and allelic frequency at position - 174（ G/ C） in the promoter of IL-6 gene（ genotype： X2 = 25.75, P 〈 0.001 ; allele： X2 = 25.99, P 〈0.001 ）. The frequency of - 174 C allele in RA patients was significantly higher than that in normal controls（ OR = 2.26, 95% CI： 1.91-2.68）. Conclusions The polymorphisms of the promoter region of IL-6 gene at position - 572 and - 174 are closely associated with RA in the Chinese HaM population of Guangdong province. Allele G at position - 572 in the promoter of IL-6 gene may be associated with a protective effect against development of RA. Allele C at position - 174 is associated with susceptibility to pathogenesis of RA.