Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan

Abstract

Objective: A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. Method: A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 5[rs597980], ST + 4[rs44707], S2[rs528557], Q − 1[rs612709], and F + 1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Results: Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p = 0.0189, Genotype p = 0.021). SNPs T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 4[rs44707], S2[rs528557], and Q − 1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype “AAGTCG” in healthy controls suggests a protective effect against asthma risk in the studied population (p = 0.0059). Conclusion: These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.

• ADAM33
• single nucleotide polymorphisms
• asthma
• linkage disequilibrium
• haplotype
• mini sequencing
• Punjabi
• Pakistan

Acknowledgements

The authors are grateful to Dr. Iqbal Bano, Children Hospital, Lahore, for her extreme cooperation in collecting the blood sample and Ms. Farheena Iqbal, Ms. Asma Mateen for their technical help and cooperation in the DNA Core Facility labs, CAMB, Lahore. We are really thankful to Dr. David Eccles (Gringene Bioinformatics) for his expert advice on the statistical analysis carried out in this study. Thanks to Dr. Mary Chaiken for refining the manuscript and valuable review.

Declaration of interest

The authors declare no conflict of interest. The study was mainly sponsored by Centre for Applied Molecular Biology (CAMB), Lahore, Pakistan.