Turk J Immunol. 2020; 8(3): 103-112 | DOI: 10.25002/tji.2020.1235

IL-10-592 A/C Gene Polymorphism and Cytokine Levels are Associated with Susceptibility to Drug Resistance in Tuberculosis

Atefeh Sadeghi Shermeh¹, Majid Khoshmirsafa¹, Ali-akbar Delbandi¹, Payam Tabarsi³, Esmaeil Mortaz³, Mohammad Reza Bolouri¹, Elham Alipour Fayez¹, Farhad Seif⁴, Mehdi Shekarabi^1
1Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
²Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
³Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
⁴Department of Immunology & Allergy, Academic Center for Education, Culture, and Research, Tehran, Iran

INTRODUCTION: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the
community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the
world health organization (WHO). Cytokines play important roles in the relationship between the immune system
and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and
function against TB.
METHODS: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of
these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB
patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug
sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was
used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group.
RESULTS: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically
significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs
(p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups
(p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874.
DISCUSSION AND CONCLUSION: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility
to DR-TB. However, further investigation is necessary.

Keywords: Polymorphism, IFN-γ,, IL-10, tuberculosis, drug-resistant tuberculosis

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Sitokin Seviyelerinin ve IL-10-592 A/C Polimorfizminin Tüberkülozda Ýlaç Direnci ile Ýliþkisi

Atefeh Sadeghi Shermeh¹, Majid Khoshmirsafa¹, Ali-akbar Delbandi¹, Payam Tabarsi³, Esmaeil Mortaz³, Mohammad Reza Bolouri¹, Elham Alipour Fayez¹, Farhad Seif⁴, Mehdi Shekarabi^1
1
2
3
4

GÝRÝÞ ve AMAÇ: Tüberküloz (TB) ve özellikle dirençli tiplerinin taný ve tedavisi halk saðlýðý sistemine önemli bir ekonomik yüke
neden olmaktadýr. Bu neden ile, bu konuda araþtýrma yapýlmasý Dünya Saðlýk Örgütü (DSÖ) tarafýndan önceliði
olduðu bildirilen bir konudur. Sitokinleri baðýþýklýk sistemi ve tüberkülozda önemli rol oynamaktadýr. Özellikle tek
nükleotidde saptanan polimorfizmlerin (TNP) olduðu genetik farklýlýklar tüberküloza karþý baðýþýklýk ve sitokin
üretiminde etkilidir.
YÖNTEM ve GEREÇLER: Bu çalýþmada, 87 hasta ve 100 saðlýklý bireyde IFN-γ (+874 T/A) ve IL-10 (-592 A/C)’un
genlerinin TNP’leri ve bu TNP’lerin oluþan sitokinlerin salýnýmýna olan etkileri irdelendi. TB hastalarý 2 ayrý gruba
ayrýldý: Polimeraz zincir tepkimesi (PZT) ile ilaca hassas (ÝH) olduðu belirlenen 67 ve ilaca dirençli (ÝD) olduðu
saptanan 20 tüberkülozlu hasta.TNP’ni saptamada PZT temelli bir metod, IFN-γ ve IL-10 düzeyleri için ise, ELISA
yöntemi kullanýldý.
BULGULAR: Saðlýklý bireyler ve ÝD TB hastalar arasýnda -592A/C TNP açýsýndan istatistiksel açýdan anlamlý farklýlýk
saptandý (p=0.011). Akciðer tüberkülozu olan olgulardaki IL-10 düzeyleri saðlýklý bireylerdekine göre yüksek olarak
saptandý (p=0.02). ÝH TB hastalarýnda serum IFN-γ düzeylerinin diðer gruplardakine göre daha yüksek olduðu saptandý
(p<0.001); buna karþýn bu hastalarda IFN-γ 874 polimorfizmi açýsýndan allel ya da genotip farklýlýðý bulunmadý.
TARTIÞMA ve SONUÇ: Çalýþmamýz, IL-10 geninin 592.pozisyonundaki TNP’nin ÝD-TB ile ilgili olabileceðini düþündürtmektedir.
Ancak, ileri çalýþmalara gerek duyulmaktadýr.

Anahtar Kelimeler: Polimorfizm, IFN-γ,, IL-10, tüberküloz, ilaca dirençli tüberküloz

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