Analysis of Risk Factors in Patients with Bronchial Asthma: Genetic Markers and Comorbid Metabolic Disorders

Introduction. Bronchial asthma (BA) is a heterogeneous disease whose development involves not only genetic predisposition but also important non-hereditary factors, including comorbid conditions such as type 2 diabetes mellitus (T2DM) and metabolic syndrome. The shared pathogenetic mechanisms based on chronic inflammation suggest the existence of common genetic determinants, which remains understudied.

Purpose. To identify molecular genetic markers and risk factors for predisposition to adult-onset BA associated with metabolic disorders.

Materials and Methods. A retrospective case-control study was conducted on a sample of 315 individuals (63 BA patients and 252 conditionally healthy controls), matched for age and sex. Alongside the analysis of concomitant pathology, an association analysis was performed for polymorphisms in the genes: ADRB2 (rs1042713), IL6 (rs1800795), HLA-DQ2.5 (rs2187668), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). Statistical analysis was performed using the χ² criterion in the StatTech v. 4.12.1 program (developer – StatTech LLC, Russia).

Results. BA patients had a significantly higher prevalence of diabetes/metabolic syndrome-associated disorders (11.1 % vs. 4.0 %, p = 0.034) and diagnosed colitis (14.3 % vs. 3.6 %, p = 0.003). Strong associations with BA were found for polymorphisms in genes key to metabolism: SLC30A8 rs13266634 (C/C genotype: 41.3 % vs. 11.5 %, p < 0.001) and TCF7L2 rs12255372 (G/G genotype: 47.6 % vs. 14.3 %, p < 0.001). No associations were found for polymorphisms in the ADRB2, IL6, and HLA-DQ2.5 genes. Research limitations. The retrospective design and the relatively small sample size, which preclude establishing causal relationships.

Conclusion. The obtained data indicate the existence of a "metabolically-associated" phenotype of adult-onset BA, whose pathogenesis is significantly linked to polymorphisms in the SLC30A8 and TCF7L2 genes and corresponding comorbidity. The results justify the expediency of mutual screening of BA patients for metabolic disorders and inflammatory bowel diseases.

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