PTPN22基因多态性与自身免疫甲状腺病的相关性

目的:检测PTPN22基因的单核苷酸多态性(SNP)及其与中国人自身免疫甲状腺病(AITD)的相关性, 并研究CTLA- 4基因SNP与PTPN22 SNP的相互关系.方法:采用PCR-RFLP技术分析231例AITD患者, 其中Graves'病(GD)149例, 桥本甲状腺炎(HT)82例和131例健康对照者PTPN22基因 1858 C>T及CTLA- 4基因49A>G位点的基因型.采用SASP-PCR技术分析PTPN22基因启动子-1123G>C的基因型.结果:(1)PTPN22基因的 1858C>T位点不存在多态性;(2)PTPN22基因-1123G>C SNP的等位基因和基因型分布频率在GD组与正常对照组间的差异有统计学意义(P值分别为0.040和0.013, OR值分别为1.44和2.33);(3) CTLA- 4基因 49A>G位点的等位基因和基因型分布频率在AITD组与正常组间有明显差异;(4)与携带PTPN22的G等位基因及CTLA- 4的AA基因型者相比, 携带PTPN22CC基因型与CTLA- 4 AG或GG基因型者发生GD的OR值=3.31(95%CI: 2.69-8.89).结论:PTPN22基因启动子-1123G>C SNP与GD的发生相关, 其CC基因型与CTLA- 4基因的G 等位基因对GD的发生起协同作用.

Association of polymorphism of protein tyrosine phosphatase nonreceptor-22 gene with AITD

AIM: To evaluate the association of PTPN22 gene polymorphism with autoimmune thyroid disease (AITD) in Chinese people and to analyze the relationship between SNP of CTLA-4 gene and SNP of PTPN22 gene. METHODS: 149 patients with Graves' disease (GD) and 82 patients with Hashimoto's thyroiditis (HT) as well as 131 healthy people as controls were investigated. PTPN22 gene polymorphism +1858 C>T and CTLA-4 gene polymorphism 49A>G were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PTPN22 gene polymorphism -1123G>C at promoter was genotyped by single allele-specific primer polymerase chain reaction (SASP-PCR). RESULTS: (1) +1858C>T for PTPN22gene was not polymorphic enough in patients and controls. (2) Statistic differences in alleles and genotype frequency of -1123G>C were observed between GD patients and controlsèP=0.040, 0.013; OR=1.44, 2.33, respectivelyé. (3) Differences in alleles and genotype frequency of 49A>G for CTLA-4 gene were observed in patients and controls. (4) Individuals with PTPN22 CC genotype and CTILA-4 G alleles had an increased risk of developing GD (OR=3.31, 95%CI: 2.69-8.89) compared with those with PTPN22 G alleles and CTLA-4 AA genotype. CONCLUSION: -1123 G>C SNP of PTPN22 gene is associated with GD. There is coordination between PTPN22 CC genotype and CTLA-4 G alleles in the development of GD.