Genetic Diversity of IFγ, IL1β, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan

Dauren Yerezhepov, Axat Zhabagin, Ayken Askapuli, Saule Rakhimova, Zhannur Nurkina, Aliya Abilmazhinova, Alma Akhmetova, Askhat Molkenov, Ulykbek Kairov, Ainur Akilzhanova

Research output: Contribution to journalArticle

Abstract

Introduction: Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.

Methods: 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1β (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19.

Results: Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M - 41.5%/1.3%) and G/G in males (M/F - 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group.

Conclusion: Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.

Original languageEnglish
Pages (from-to)181
JournalCentral Asian journal of global health
Volume3
Issue numberSuppl
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Kazakhstan
Pulmonary Tuberculosis
Genotype
Tuberculosis
Lung
Microbial Genetics
Population
Bacteria
Latent Tuberculosis
Multidrug-Resistant Tuberculosis
Mycobacterium tuberculosis
Genes
Medical Records
Case-Control Studies
Interviews
Control Groups
DNA

Cite this

@article{39bcd877a994421fa9507b5b56049adb,
title = "Genetic Diversity of IFγ, IL1β, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan",
abstract = "Introduction: Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30{\%} of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.Methods: 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39{\%} and 57.61{\%}, respectively. Of all participants, 67.4{\%} were Kazakhs, 22.8{\%} Russians, 3.4{\%} Ukrainians, and 6.4{\%} were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1β (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19.Results: Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M - 41.5{\%}/1.3{\%}) and G/G in males (M/F - 49{\%}/20.7{\%}) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95{\%}, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95{\%}, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95{\%}, CI: 1.18 - 2.83, p = 0.036) in males of the control group.Conclusion: Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.",
author = "Dauren Yerezhepov and Axat Zhabagin and Ayken Askapuli and Saule Rakhimova and Zhannur Nurkina and Aliya Abilmazhinova and Alma Akhmetova and Askhat Molkenov and Ulykbek Kairov and Ainur Akilzhanova",
year = "2014",
doi = "10.5195/cajgh.2014.181",
language = "English",
volume = "3",
pages = "181",
journal = "Central Asian journal of global health",
issn = "2166-7403",
number = "Suppl",

}

TY - JOUR

T1 - Genetic Diversity of IFγ, IL1β, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan

AU - Yerezhepov, Dauren

AU - Zhabagin, Axat

AU - Askapuli, Ayken

AU - Rakhimova, Saule

AU - Nurkina, Zhannur

AU - Abilmazhinova, Aliya

AU - Akhmetova, Alma

AU - Molkenov, Askhat

AU - Kairov, Ulykbek

AU - Akilzhanova, Ainur

PY - 2014

Y1 - 2014

N2 - Introduction: Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.Methods: 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1β (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19.Results: Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M - 41.5%/1.3%) and G/G in males (M/F - 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group.Conclusion: Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.

AB - Introduction: Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.Methods: 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1β (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19.Results: Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M - 41.5%/1.3%) and G/G in males (M/F - 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group.Conclusion: Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.

U2 - 10.5195/cajgh.2014.181

DO - 10.5195/cajgh.2014.181

M3 - Article

C2 - 29805910

VL - 3

SP - 181

JO - Central Asian journal of global health

JF - Central Asian journal of global health

SN - 2166-7403

IS - Suppl

ER -