D1.120 - Genetic Associations with Asthma in the Kazakh Population: A Case–Control Study

Asthma is a chronic inflammatory airway disease with a substantial global burden and increasing prevalence in Central Asia, including Kazakhstan. While environmental factors contribute to disease development, genetic susceptibility plays a crucial role in asthma onset and phenotypic heterogeneity. However, data on asthma-associated genetic variants in Central Asian populations remain limited. This study aimed to investigate genetic variants associated with asthma susceptibility in the Kazakh population, focusing on single nucleotide polymorphisms (SNPs) within the ACTN3 and TSBP1 genes.

A case–control study was conducted including 600 adults: 300 patients with physician-diagnosed asthma and 300 healthy controls. Genomic DNA was extracted from peripheral blood samples. A total of 120 SNPs were selected based on prior evidence of involvement in asthma-related pathways. Genotyping was performed using the QuantStudio™ 12K Flex Real-Time PCR System. Allele and genotype frequencies were compared using χ² tests, and odds ratios (ORs) with 95% confidence intervals were calculated to assess associations between genetic variants and asthma risk.

Two SNPs demonstrated strong associations with asthma. The G allele of rs540874 in the ACTN3 gene was significantly more frequent in asthma patients than in controls (minor allele frequency 0.71 vs. 0.30; p = 4.78 × 10⁻¹⁴). Similarly, the G allele of rs3132954 in the TSBP1 gene was associated with increased asthma susceptibility (minor allele frequency 0.54 vs. 0.10; p = 1.33 × 10⁻¹²). In both loci, the A/A genotype was more prevalent among controls, suggesting a potential protective effect.

This study identifies significant genetic associations between asthma and variants in the ACTN3 and TSBP1 genes in the Kazakh population. These findings extend current evidence on population-specific genetic susceptibility to asthma and may inform future studies exploring functional mechanisms and personalized approaches to asthma management.