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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. 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. 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 &lt;  .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 &lt;  .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. The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly ( p -values &lt;  .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

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