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

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Abstract

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.

Methods

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.

Results

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).

Conclusions

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.

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