Sequence variants on 17q21 are associated with the susceptibility of asthma in the population of Lahore, Pakistan

Abstract

Objective: Single nucleotide polymorphisms (SNPs) on 17q21 are known to be associated with asthma disease in multiple populations. This study was designed to know whether this region is associated with asthma in Lahore region population or not. Methods: A total of 200 asthma patients and 100 healthy controls were enrolled from different hospitals of Lahore, Pakistan. Twelve SNPs from chromosomal region 17q21 were analyzed in cases and controls by single base extension method and capillary-based genetic analyzers. Associations with asthma were checked using basic allelic model, genotypic model, and results were adjusted by logistic regression analysis using PLINK v1.9. Pair-wise linkage disequilibrium among the SNPs was analyzed by using Haploview software. Results: SNP rs3816470 showed a strong association (p = 8.89 × 10⁻⁵, Odd Ratio = 3.082 [1.755-5.41]) with asthma, whereas rs3859192 and rs6503525 also showed a significant association with the development of asthma, especially in the case of positive family history. In LD block1 (93 kb) consisting of six SNPs (rs12936231, rs7216389, rs7216558, rs9894164, rs1007654 and rs7212938), none of the haplotypes show any significant association with asthma except the haplotype “CCTCAG”, which is a significant protective factor against asthma having frequency 0.051 in controls while 0.017 in cases (p = 3.56 × 10⁻², χ² = 4.415). Conclusion: The present study reports that the polymorphic genomic variant rs3816470 is significantly and independently associated with asthma in the studied population, while the variants, rs6503525 and rs3859192, also indicate a significant association with asthma in this population when family history of the disease is taken as a covariate.

• Case control study protective factor, genetics, LD, haplotype, single nucleotide polymorphism, single base extension

Acknowledgements

The authors are grateful to Dr Asim Raza, Ms. Farheena Iqbal, Ms. Asma Tariq and Ms. Samra Kousar for their technical help and cooperation in the DNA Core Facility labs. We are really thankful to Dr David Eccles (Gringene Bioinformatics) for his expert advice on the statistical analysis carried out in this study and Dr Usman Ali Ashfaq for refining the manuscript.

Declaration of interest

The authors declare no conflicts of interest.

The study was mainly sponsored by Higher Education Commission, Pakistan and partially by Centre for Applied Molecular Biology, Ministry of Science and Technology, Lahore, Pakistan and Centre of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan.

Supplementary material available online

Supplementary Tables S1, S2 and S3.