Department of Clinical Pathology, Faculty of Medicine, Tanta University, Egypt.
Department of Clinical Pathology, Faculty of Medicine, Tanta University, Egypt.
Gene. 2020 Apr 30;736:144419. doi: 10.1016/j.gene.2020.144419. Epub 2020 Feb 1.
To evaluate the relationship between two common single nucleotide polymorphisms (SNPs) of CD40 gene (rs1883832 C/T and rs4810485 G/T) and the risk of immune thrombocytopenia (ITP) in the Egyptian population.
A case-control study was conducted retrospectively on 101 cases with ITP and 97 healthy subjects. Two SNPs of CD40 gene (rs1883832 C/T and rs4810485 G/T) were genotyped via Taqman allele discrimination real-time PCR. The frequencies of different genetic models of both SNPs were calculated and compared between ITP cases and controls. Linkage analysis was performed between the studied SNPs. Odds ratio (OR) and 95% confidence interval (CI) were assessed using multinomial logistic regression analysis to determine the association of CD40 gene SNPs genotypes, alleles, and haplotypes with the risk of ITP. The odds ratio was further adjusted to the confounders for risk stratification.
CD40 (rs1883832) TT genotype carriers have a significantly higher risk of ITP when compared to CC genotype carriers (adjusted OR: 3.792, 95%CI: 1.252-11.49, P = 0.018). T allele also represents 1.711-fold increased risk of ITP which is more evident in males (P = 0.016). No significant difference was observed in the frequency of CD40 (rs4810485 G/T) genetic models between cases and controls. Linkage disequilibrium was found between the two SNPs and revealed four main haplotypes (C-G; C-T; T-G; T-T) with a significantly higher frequency of T-G haplotype in ITP cases than in healthy controls which confers an increased risk of ITP development (OR: 2.349, 95%CI: 1.271-4.339, P = 0.006).
CD40 gene SNP rs1883832 is associated with an increased risk of ITP development in the Egyptian population, while the SNP rs4810485 has no association. Moreover, T-G haplotype is a risk genetic model for ITP.
评估 CD40 基因（rs1883832 C/T 和 rs4810485 G/T）两个常见单核苷酸多态性（SNP）与埃及人群免疫性血小板减少症（ITP）风险的关系。
采用回顾性病例对照研究，纳入 101 例 ITP 患者和 97 名健康对照。采用 Taqman 等位基因鉴别实时 PCR 检测 CD40 基因（rs1883832 C/T 和 rs4810485 G/T）两个 SNP。计算并比较病例和对照组中两种 SNP 的不同遗传模型的频率。对研究 SNP 进行连锁分析。采用多变量逻辑回归分析评估优势比（OR）和 95%置信区间（CI），以确定 CD40 基因 SNP 基因型、等位基因和单体型与 ITP 风险的关联。进一步将 OR 调整为风险分层的混杂因素。
与 CC 基因型携带者相比，CD40（rs1883832）TT 基因型携带者患 ITP 的风险显著增加（校正 OR：3.792，95%CI：1.252-11.49，P=0.018）。T 等位基因也代表 ITP 风险增加 1.711 倍，在男性中更为明显（P=0.016）。病例和对照组之间 CD40（rs4810485 G/T）遗传模型的频率无显著差异。两个 SNP 之间存在连锁不平衡，共发现四个主要单体型（C-G；C-T；T-G；T-T），与健康对照组相比，ITP 患者中 T-G 单体型频率显著升高，提示 T-G 单体型与 ITP 发病风险增加相关（OR：2.349，95%CI：1.271-4.339，P=0.006）。
CD40 基因 SNP rs1883832 与埃及人群 ITP 发病风险增加相关，而 SNP rs4810485 与 ITP 无关。此外，T-G 单体型是 ITP 的风险遗传模型。
