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

Background Asthma 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.

A 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.

The 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).

The 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved ethically and scientifically by the directorate of post-grad and scientific research in the University of Aleppo, syria (2018-2019) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Statement The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request, subject to appropriate ethical approvals and data sharing agreements.