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Association of Chemokine Genes CXCL9 and CXCL10 Polymorphisms with Tuberculosis in Pakistani Population

Association of Chemokine Genes CXCL9 and CXCL10 Polymorphisms with Tuberculosis in Pakistani Population

Saleha Tabassum1, Muneeza Zafar1,2, Munazza Raza Mirza1*, Muhammad Iqbal Choudhary1,3, Ikram ul Haq4, Imran Riaz Malik2, Ambreen Ansari1 and Mehtab Alam5

1Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, 75270, Pakistan.
2University of Sargodha, Sargodha, Pakistan.
3H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, 75270, Pakistan. 
4Institute of Biotechnology and Genetic Engineering, University of Sindh, Jamshoro, Pakistan.
5Department of Biochemistry, Dow University of Medical and Health Sciences, Ojha Campus. Karachi, Pakistan.
 
Saleha Tabassum and Muneeza Zafar equally contributed and are co-first authors.
 
* Corresponding author: munzihyder@yahoo.com

ABSTRACT

The CXCR3 ligand family, including CXCL9, CXCL10 and CXCL11, play important role in T-cell, natural killer (NK) cell, NKT cell and dendritic cell trafficking. These chemokines were suggested for their use as alternative markers for TB diagnosis, and their possible involvement in disease pathophysiology. In the present study, we investigated the genetic association and frequency of CXCL9 and CXCL10 genes polymorphisms in TB patients of Pakistani population. A total of 260 study participants, including 122 with tuberculosis disease (TB) and 138 healthy control (HC) were included. Out of these 122 TB disease subjects (67%) were diagnosed with PTB (n = 82) and 33% with EPTB (n = 40). Tri and Tetra- ARMS-PCR techniques were used to genotype rs2276886 of CXCL9 and rs5606198 of CXCL10 for all the samples. The results showed significant association (OR, 2.1 (0.99 to 4.30), p = 0.04) of A allele of rs2276886 with EPTB group as compared to the control. In genetic model analysis, we found strong association (OR, 0.4 (0.181 to 0.94), p = 0.03) of GG genotype with male with EPTB as compared to female in gender stratified dominant model. Furthermore, in context of different ethnic groups of Pakistani subpopulation, we found Punjabi speaking’s to be significantly at higher risk (OR, 2.16 (95%CI, 1.0910 to 4.2901), p = 0.02) of developing TB as compared to other ethnic categories. Strong association of CXCL9 polymorphism (rs2276886 G>A) with TB disease in Pakistani population was concluded especially, Punjabi speaking participants were found to have higher risk of developing TB.

 

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Pakistan Journal of Zoology

October

Vol. 54, Iss. 5, Pages 2003-2500

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