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

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.

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Keywords:

• Asthma
• 17q21 variants
• polymorphisms
• association studies
• Pashtun
• Pakistan

Acknowledgements

We would like to extend our thanks to Dr. Nafees Ahmed (IBGE, Islamabad), Dr. Sami Siraj, and the clinicians of the Khyber Medical University for their help and support in this study.

Declaration of interest

The authors report no conflict of interest and they are responsible for the content and writing of this article.

Additional information

Funding

Not applicable.