Pulmonary tuberculosis epidemiology and genetics in Kazakhstan

Dauren Yerezhepov; Aidana Gabdulkayum; Ainur Akhmetova; Ulan Kozhamkulov; Saule Rakhimova; Ulykbek Kairov; Gulnur Zhunussova; Ruslan Kalendar; Ainur Akilzhanova

doi:10.3389/fpubh.2024.1340673

Pulmonary tuberculosis epidemiology and genetics in Kazakhstan

Front Public Health. 2024 Apr 19:12:1340673. doi: 10.3389/fpubh.2024.1340673. eCollection 2024.

Authors

Dauren Yerezhepov¹, Aidana Gabdulkayum¹, Ainur Akhmetova¹, Ulan Kozhamkulov¹, Saule Rakhimova¹, Ulykbek Kairov², Gulnur Zhunussova³, Ruslan Kalendar², Ainur Akilzhanova¹

Affiliations

¹ Laboratory of Genomic and Personalized Medicine, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.
² Laboratory of Bioinformatics and Systems Biology, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.
³ Institute of Genetics and Physiology, Almaty, Kazakhstan.

Abstract

Background: Tuberculosis (TB) is a major public health emergency in many countries, including Kazakhstan. Despite the decline in the incidence rate and having one of the highest treatment effectiveness in the world, the incidence rate of TB remains high in Kazakhstan. Social and environmental factors along with host genetics contribute to pulmonary tuberculosis (PTB) incidence. Due to the high incidence rate of TB in Kazakhstan, our research aimed to study the epidemiology and genetics of PTB in Kazakhstan.

Materials and methods: 1,555 participants were recruited to the case-control study. The epidemiology data was taken during an interview. Polymorphisms of selected genes were determined by real-time PCR using pre-designed TaqMan probes.

Results: Epidemiological risk factors like diabetes (χ² = 57.71, p < 0.001), unemployment (χ² = 81.1, p < 0.001), and underweight-ranged BMI (<18.49, χ² = 206.39, p < 0.001) were significantly associated with PTB. VDR FokI (rs2228570) and VDR BsmI (rs1544410) polymorphisms were associated with an increased risk of PTB. A/A genotype of the TLR8 gene (rs3764880) showed a significant association with an increased risk of PTB in Asians and Asian males. The G allele of the rs2278589 polymorphism of the MARCO gene increases PTB susceptibility in Asians and Asian females. VDR BsmI (rs1544410) polymorphism was significantly associated with PTB in Asian females. A significant association between VDR ApaI polymorphism and PTB susceptibility in the Caucasian population of Kazakhstan was found.

Conclusion: This is the first study that evaluated the epidemiology and genetics of PTB in Kazakhstan on a relatively large cohort. Social and environmental risk factors play a crucial role in TB incidence in Kazakhstan. Underweight BMI (<18.49 kg/m2), diabetes, and unemployment showed a statistically significant association with PTB in our study group. FokI (rs2228570) and BsmI (rs1544410) polymorphisms of the VDR gene can be used as possible biomarkers of PTB in Asian males. rs2278589 polymorphism of the MARCO gene may act as a potential biomarker of PTB in Kazakhs. BsmI polymorphism of the VDR gene and rs2278589 polymorphism of the MARCO gene can be used as possible biomarkers of PTB risk in Asian females as well as VDR ApaI polymorphism in Caucasians.

Keywords: epidemiology; genetic predisposition; immune response; infectious disease; pulmonary tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Case-Control Studies
Female
Genetic Predisposition to Disease
Genotype
Humans
Incidence
Kazakhstan / epidemiology
Male
Middle Aged
Polymorphism, Single Nucleotide
Receptors, Calcitriol* / genetics
Risk Factors
Tuberculosis, Pulmonary* / epidemiology
Tuberculosis, Pulmonary* / genetics

Substances

Receptors, Calcitriol
VDR protein, human

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research has been funded by the Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan (Grant No. AP09058217) and Nazarbayev University under the Collaborative Research Program (Grant No 11022021CRP1511, UK).