Association of ADAM33 Gene rs2280091 (T1) Polymorphism with Asthma Severity in Syrian Population: A Case-Control Study Using PCR-RFLP Analysis

BackgroundAsthma is a complex chronic inflammatory disease affecting approximately 339 million people worldwide. The ADAM33 gene, encoding a disintegrin and metalloproteinase, has emerged as a key susceptibility gene for asthma, with the rs2280091 (T1) polymorphism showing variable associations across different populations. This study represents the first genetic investigation of asthma in the Syrian population. MethodsA case-control study was conducted at Aleppo University Hospital from April to November 2019, including 100 participants (80 asthma patients and 20 healthy controls) aged 20-40 years. Asthma diagnosis was confirmed using spirometry and reversibility testing according to GINA guidelines. Genomic DNA was extracted from whole blood, and the rs2280091 polymorphism was genotyped using PCR-RFLP with NcoI restriction enzyme. Statistical analysis was performed using SPSS 25.0 with significance set at p[≤]0.05. ResultsThe study population showed balanced sex distribution (50% male, 50% female) with mean ages of 26.13 years (cases) and 29.65 years (controls). Genotype frequencies were: A/A (43.0%), A/G (45.0%), and G/G (12.0%), with allele frequencies of A=0.66 and G=0.34, conforming to Hardy-Weinberg equilibrium. While no significant association was found between genotype and asthma occurrence (p=0.871), the G/G genotype showed significant association with increased asthma severity (p=0.016). ANOVA analysis revealed significantly lower FEV1 values in G/G carriers compared to A/A and A/G genotypes (p=0.001). ConclusionsThe ADAM33 rs2280091 G/G genotype is significantly associated with increased asthma severity in the Syrian population, suggesting its potential utility as a genetic marker for severe asthma phenotypes. This finding contributes to understanding asthma genetics in Middle Eastern populations and supports the role of ADAM33 in airway remodeling processes.