Impact of CD40 gene polymorphisms on the risk of immune thrombocytopenic purpura

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.