Association between 17q21 variants and asthma predisposition in Pashtun population from Pakistan

Sibtain Afzal; Khushnooda Ramzan; Sajjad Ullah; Arshad Jamal; Sulman Basit; Khaled M AlKattan; Ahmed Bilal Waqar

doi:10.1080/02770903.2021.2025391

Association between 17q21 variants and asthma predisposition in Pashtun population from Pakistan

J Asthma. 2023 Jan;60(1):63-75. doi: 10.1080/02770903.2021.2025391. Epub 2022 Jan 26.

Authors

Sibtain Afzal^{1

2}, Khushnooda Ramzan³, Sajjad Ullah¹, Arshad Jamal^{1

4}, Sulman Basit⁵, Khaled M AlKattan², Ahmed Bilal Waqar^{1

6}

Affiliations

¹ Department of Medical Laboratory Sciences, Faculty of Allied & Health Sciences, Imperial College of Business Studies, Lahore, Pakistan.
² College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
³ Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
⁴ Biology Department, College of Science, University of Hail, Kingdom of Saudi Arabia.
⁵ Center for Genetics and Inherited Diseases, Taibah University, Madinah Al-Munawarah, Saudi Arabia.
⁶ University Institute of Medical Laboratory Technology, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.

PMID: 34982638
DOI: 10.1080/02770903.2021.2025391

Abstract

Objective: Asthma is a heterogeneous and genetically complex respiratory disease, and more than 300 million people are affected worldwide. In this study, frequencies of four SNPs (rs3816470, rs7216389, rs8067378, rs12603332) in chromosome 17q21 region were analyzed and their relationship with the asthma susceptibility, in the Pashtun population of Khyber Pakhtunkhwa province (KPK) of Pakistan were investigated.

Methods: DNA samples from 500 subjects (asthma cases/controls) were genotyped by Sanger sequencing. Chi-square tests, logistic regression analysis, linkage disequilibrium, and haplotype analysis techniques were applied to study the association of the SNPs with asthma.

Results: Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive, were tested. The frequencies of alleles T/T at rs3816470 (OR = 1.91; 95%CI = 1.15-3.18; p = .011*) and rs7216389 (OR = 2.14; 95%CI = 1.21-3.79; p = .0076*), A/A at rs 8067378 (OR = 1.89; 95%CI = 1.17-3.06; p = .0081*), C/C at rs12603332 (OR = 1.97; 95%CI = 1.18-3.27; p = .008*), under recessive models, respectively, were significantly (p-values < .0125) associated with asthma susceptibility. The frequencies of T/T genotype in rs3816470 (OR = 6.01; 95%CI = 2.48-14.60; p = .000147*), and rs7216389 (OR = 5.05; 95%CI = 1.79-14.21; p = .003296*), and C/C at rs12603332 (OR = 2.64; 95%CI = 1.11-6.32; p = .019063*), were significantly (p-values < .0125) associated with asthma susceptibility in Pashtun women by stratified analysis based on age and gender. Similarly, three unique haplotypes were found associated with disease development and protective effect in female and male subjects. Linkage disequilibrium analysis presented a strong linkage (≥80%) between SNP variants and predicted their co-inheritance in the studied population.

Conclusion: The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly (p-values < .0125) associated with asthma predisposition in the Pashtun population of KPK exclusively in the female asthmatic cases.

Supplemental data for this article can be accessed.

Keywords: 17q21 variants; Asthma; Pakistan; Pashtun; association studies; polymorphisms.

MeSH terms

Asthma* / epidemiology
Asthma* / genetics
Case-Control Studies
Female
Genetic Predisposition to Disease*
Genotype
Humans
Male
Pakistan / epidemiology
Polymorphism, Single Nucleotide