【摘要】 目的探讨程序性细胞凋亡基因(programmed cell death-1,PDCD1)第5外显子单核苷酸多态性(SNP)与中国南方汉族人群系统性红斑狼疮(systemic lupus erythematosus,SLE)易感性的关系。方法采用病例对照研究设计,收集132例病例和160例对照,应用PCR-RFLP技术检测PD1.6G>A和PD1.5C>T两个位点的SNPs,运用SAS8.2软件包进行基因型、等位基因和单倍型等的关联性分析。结果对照组PD1.6G>A位点突变基因型AA频率高于SLE患者(χ2=5.123,P=0.023),患者中的A等位基因频率低于对照组(χ2=8.036,P=0.005);PD1.5C>T位点中,CT基因型在对照组中的比例较低(χ2=15.380,P=0.000),病例组的T等位基因频率高于对照组(χ2=11.631,P=0.001)。同时,两位点等位基因间存在连锁不平衡(χ2=10.708,P=0.001),且病例组和对照组单倍型分布不同(χ2=18.821,P=0.000);其中,病例组A-C单倍型频率低于对照组(χ2=15.812,P=0.000),A-T和G-T单倍型频率高于对照组(χ2=4.119,P=0.042和χ2=6.621,P=0.010)。结论在中国南方汉族人群中,PDCD1基因PD1.6G>A和PD1.5C>T两个位点多态性与SLE具有相关性,PD1.6G>A的G→A突变可能是SLE的保护因素(OR=0.57,95%CI:0.39-0.84),PD1.5C>T的C→T突变可能是SLE的危险因素(OR=2.02,95%CI:1.35-3.02)。A-T和G-T单倍型可能是SLE的易感单倍型(OR=1.58,95%CI:1.02-2.46和OR=3.02,95%CI:1.30-7.02),A-C单倍型可能是SLE的保护性单倍型(OR=0.51,95%CI:0.36-0.71)。更多还原

【Abstract】 Objective To approach the association of two single nucleotide polymorphisms (SNPs) within the exon-5 of programmed cell death-1 (PDCD1) gene and the development of systemic lupus erythematosus(SLE) in Southern Chinese Han people. Methods 132 cases and 160 normal controls were enrolled with the aim of case-control design, and SNPs of PD1.6G>A and PD1.5C>T were genotyped by PCR-RFLP.Moreover, we calculated ORs and LD as well as the frequencies of haplotypes for the two loci. Results It was found that mutated AA genotype frequency of PD1.6G>A in controls was significantly higher than the one in cases (χ2= 5.123, P=0.023), and the frequency with A alleles in patients was significantly decreased relative to the one in healthy controls (χ2=8.036, P=0.005). In PD1.5C>T, CT frequency in controls was lower than the one in cases with statistically significance (χ2=15.380, P=0.000), and the carrier frequency of T allele in cases was significantly increased compared with controls (χ2=11.631, P=0.001). Moreover, there were linkage disequilibriums between alleles of PD1.6G>A and PD1.5 C>T (χ2=10.708, P=0.001). The haplotype distributions between cases and controls were significantly different in PDCD1(χ2=18.821, P=0.000), with relative higher proportion of A-T and G-T haplotypes (χ2=4.119, P=0.042; χ2=6.621, P=0.010) and less proportion of A-C haplotype (χ2=15.812, P=0.000) in SLE group. Conclusions The polymorphisms of PD1.6G>A and PD1.5C>T were associated with SLE in Southern Chinese Han people. The mutation of GA in PD1.6G>A might be protective from SLE (OR = 0.57, 95% CI: 0.39-0.84), while the CT mutation in PD1.5C>T might be harmful (OR=2.02, 95% CI: 1.35-3.02). The haplotypes of A-T and G-T might be susceptible to SLE (OR=1.50, 95% CI: 1.02-2.46 and OR=3.02, 95% CI: 1.30-7.02), and the A-C haplotype might play a protective role in development of SLE (OR=0.51, 95% CI: 0.36-0.71).更多还原