Impact of ADRB2 gene polymorphisms and environmental factors Exposure on asthma control in adolescents from Pakistan
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Abstract
Objective: To explore the association of ADRB2 Gly16Arg (rs1042713) and Gln27Glu (rs1042714) polymorphisms with asthma control in Pakistani adolescents and explore potential interactions with environmental exposures like tobacco smoke and air pollution.
Methods: This cross-sectional study was conducted from January-June 2022 at Liaquat University Hospital, Jamshoro, and affiliated clinics. Adolescents aged 12–18 years with physician-diagnosed asthma (GINA-2023 criteria) were consecutively recruited. Asthma control was assessed using Urdu Asthma Control Test (ACT; score ≤19 = uncontrolled). Spirometry followed ATS/ERS 2019 guidelines. Buccal swabs were used for genotyping ADRB2 variants by PCR–RFLP. Environmental exposures (tobacco smoke, biomass fuel, residential proximity to roads/industry) were recorded. Associations were analyzed using χ² tests, t-tests, and multivariate logistic regression adjusting for confounders. Gene–environment interactions were examined with interaction terms.
Results: Of 100 adolescents (mean age 14.6±1.9 years; 50% female), 54% had uncontrolled asthma. Arg16 allele frequency was 39% and Glu27 allele 22%. Uncontrolled asthma was significantly associated with Arg16 (χ²=5.12, p=0.024), but not Gln27Glu (p=0.31). Compared with controlled asthma, uncontrolled cases had lower ACT scores (16.5 vs. 20.7, p<0.001) and reduced FEV₁ (77.5% vs. 87.4%, p=0.008). Tobacco smoke exposure independently predicted poor control (AOR 2.51; 95% CI 1.08–5.84; p=0.032). Arg16 carriers exposed to smoke had the highest risk (AOR 3.12; 95% CI 1.01–9.61; p=0.048).
Conclusion: ADRB2 Arg16 variant was linked with poor asthma control, especially with household tobacco smoke, indicating gene–environment interaction. No significant effect was observed for Gln27Glu. Larger longitudinal studies are warranted.
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