Association of TSLP Gene’s SNP Variants with Asthma Disease in Pakistan
Association of TSLP Gene’s SNP Variants with Asthma Disease in Pakistan
Zohair Mehdi1, Ifrah Khalid1, Iqbal Bano2, Muhammad Usman Ghani1*, Muhammad Farooq Sabar1, Muhammad Umer Khan3, Hafiz Muzzammel Rehman4, Mureed Hussain5, Sadia Anjum1, Ayesha Mumtaz1, Iram Amin6 and Mariam Shahid6
ABSTRACT
Asthma is the most common chronic inflammatory disease characterized by paroxysms of dyspnea, frequent wheezing, chest tightness, and cough that varies in intensity from person to person. Thymic stromal lymphopoietin (TSLP) is a cytokine residing within the cytokine gene cluster, on locus 5q22.1, that is involved in inflammation and thus plays main role in the pathogenesis of asthma and allergic diseases. The purpose of this study was to identify the potential asthma risk single nucleotide variants (SNVs) of the TSLP gene reported in genome-wide association studies (GWAS) and evaluate the most potential asthma risk SNP in the local Punjabi population of Lahore. GWAS catalog indicated eleven single nucleotide polymorphisms (SNPs) which are significantly associated (p-value ≥ 4x10-6) with asthma disease. Out of 11 SNPs, rs1837253 (T/C) was considered the most potential asthma risk variant (p-value ≥ 4x10-6) as it was reported in 44 GWAS. A total of 97 asthma patients and 53 healthy controls were recruited for the case-control study. The target region containing the selected SNP rs1837253 (T/C) was PCR amplified and capillary-based sequencing was performed on Genetic Analyzer (3130XL). The statistical analyses were performed using SHEsis and SNPStat softwares. The statistical analysis predicted that rs1837253 SNP is significantly associated with asthma disease at the allelic level (p-value 0.038), however, “T” allele (Odds ratio 0.579) is a protective factor against asthma. The genotypic analysis also predicted a negatively significant association under the dominant inheritance model as the best-fit model (lowest AIC, p-value 0.04, Odds ratio 0.49), which showed that the persons with both homozygous “TT” and heterozygous “CT” genotypes are less susceptible to asthma disease in the studied population. This study reports the significant association of rs1837253 SNP of the TSLP gene with asthma, however, its allele “T” plays a protective role against asthma susceptibility in the Punjabi population of Lahore, Pakistan.
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