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Effects of the programmed cell death 1 (PDCD1) polymorphisms in susceptibility to systemic lupus erythematosus

机译:编程细胞死亡1(PDCD1)多态性在全身狼疮性红斑的易感性中的影响

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Abstract The failure of immunological tolerance to self‐antigens plays a fundamental role in the pathogenesis of systemic lupus erythematosus (SLE). PD‐1 is an inhibitory receptor for regulating the immune system and preventing development of autoimmune disorders. This study aimed to determine the role of four single‐nucleotide polymorphisms (SNPs) within programmed cell death 1 ( PDCD1 or PD‐1 ) gene and haplotypes defined by these SNPs in susceptibility to SLE in the Iranian population. Blood samples were obtained from 253 SLE and 564 healthy subjects. Red blood cells were lysed and genomic DNAs were extracted using salting‐out method. Genotype determinations of PD1.1, PD1.3, PD1.5 and PD1.9 SNPs were performed by polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP), and 12 haplotypes were constructed by PDCD1 SNPs. Our results showed significant differences in PD1.5 genotype frequencies between patient and control groups ( p ??.001). The frequencies of PD1.5 C/C, C/T and T/T genotypes versus other genotypes in SLE patients significantly differed from healthy subjects ( p ??.001, p ?=?.001 and p ?=?.002, respectively). Allelic analysis indicated a significant association between the frequency of PD1.5C allele and development of SLE in our population (odds ratio [OR]?=?1.91, 95% confidence interval [CI]?=?1.51–2.42, p ??.001). At the haplotype level, GGCC, GACT and GGCT haplotypes were significantly different between SLE and control groups (OR?=?2.14, 95% CI?=?1.73–2.66, p ??.001; OR?=?9.76, 95% CI?=?4.47–21.3, p ??.001; and OR?=?0.32, 95% CI?=?0.24–0.42, p ??.001, respectively). Based on these findings, PD1.5 SNP and some haplotypes of PDCD1 contribute to SLE risk in the Iranian population.
机译:摘要免疫耐受对自我抗原的失败在全身性红斑狼疮(SLE)的发病机制中起着重要作用。 PD-1是用于调节免疫系统的抑制因子,并防止自身免疫性疾病的发育。该研究旨在确定四种单核苷酸多态性(SNP)在编程的细胞死亡1(PDCD1或P​​D-1)基因和单倍型中由这些SNP定义的单倍型在伊朗人群中的易感性中的作用。从253SLE和564个健康受试者获得血样。红细胞裂解,使用盐洗方法萃取基因组DNA。通过聚合酶链反应限制片段长度多态性(PCR-RFLP)进行PD1.1,PD1.3,PD1.5和PD1.9 SNP的基因型测定,并通过PDCD1 SNP构建12个单倍型。我们的结果表明患者和对照组之间的PD1.5基因型频率显着差异(p≤001)。 PD1.5 C / C,C / T和T / T基因型的频率与SLE患者中的其他基因型与健康受试者显着不同(P?001,P?=Δ=Δ= ?.分别为002)。等位基因分析表明,PD1.5C等位基因频率与我们群体的SLE的发展之间的显着关联(赔率比[或] =?1.91,95%置信区间[CI]?=?1.51-2.42,P?& ?.001)。在单倍型水平,GGCC,GACT和GGCT单倍型在SL和对照组之间显着差异(或?=Δ2.14,95%CI?=?1.73-2.66,P?001;或?9.76, 95%ci?=α.47-21.3,p?& 001;和或?Δ= 0.32,95%ci?= 0.24-0.42,p≤00.001)。基于这些发现,PD1.5 SNP和PDCD1的一些单倍型有助于伊朗人群的SLE风险。

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