Journal of Molecular Biomarkers & Diagnosis

Association of CD40 Genotyping and its Protein Expression with Airway Inflammatory Diseases

Abstract

Shaden Muawia, Mohamed Zidan, Rasha Daabis and Mona Wagdy

CD40 plays a substantial role in inflammation and has been linked to pathogenic processes of chronic inflammatory diseases such as asthma as well as chronic obstructive pulmonary disease (COPD). Aim: The study was to investigate the association of CD40 gene (-1C/T) single nucleotide polymorphism (SNP) with the susceptibility to asthma and COPD in the Egyptian population, and its functional effect on the expression of CD40. Methods: We analyzed -1C/T SNP of the CD40 gene in 40 patients with COPD, 50 patients with asthma, and 60 normal subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CD40 expression was measured using flow cytometry. Immunoglobulin E was also determined in asthmatics. Results: The CT genotype was prevailing in the COPD patients and control group, while in the asthmatics it was the CC. Independent of the smoking status; being CC homozygous still conferred a 4-fold increase in the risk of asthma and a 2.5-fold increase in the risk of COPD. Carrying T allele showed a significantly lower risk for asthma. Furthermore, in both asthma and COPD, the least expression of CD40 protein was found with the TT genotype, which seems to have a protective effect. Despite the significant upregulation of total serum IgE in asthmatics it was not significantly associated with CD40 genotyping or the protein expression. Conclusion: Our study demonstrated that CD40 ? 1C/T polymorphism significantly contribute to the susceptibility to asthma and COPD in the Egyptian population. Reduced CD40 expression with the TT genotypes might imply that the ? 1C/T polymorphism is linked to inflammation in addition to the initiation and development of both. The genetic predisposition to certain pathways may further help to define the development of either asthma or COPD. This may lead to stratification of patients by their genetic make-up and open new therapeutic prospects.