• Muhammad Akram Centre for Applied Molecular Biology, University of the Punjab, Lahore
  • Muhammad Farooq Sabar Centre for Applied Molecular Biology, University of the Punjab, Lahore
  • Iqbal Bano The Children’s Hospital and The Institute of Child Health, Lahore
  • Muhammad Usman Ghani Centre for Applied Molecular Biology, University of the Punjab, Lahore
  • Mariam Shahid Centre of Excellence in Molecular Biology, University of the Punjab, Lahore



Asthma, Genetics, Pakistan, Single Nucleotide Polymorphism, Inflamation


Background: Candidate gene approach based on case-control model is a valuable strategy to determined disease related genetic variants. Two single nucleotide polymorphisms rs1800469 and rs2241715 in TGF-β1gene have been reported to affect the asthmatic status in different populations. The main focus of this research was to find any relationship between these SNPs and asthma in Pakistani population. Methods Using case-control model, a total of 108 individuals including 52 asthma patients and 56 healthy controls were screened to find asthma susceptibility of variants rs1800469 and rs2241715. These SNPs were genotyped using SNaPshot minisequencing assay followed by capillary electrophoresis using ABI 3130xl genetic analyzer platform. The statistical analysis of genetic data was performed by using SPSS 21, SHEsis online platform and SNPStats online web software. Results: No association with asthma was seen in allelic model for both SNPs but genotypes analyzed under codominant, dominant, over dominant and recessive models of inheritance revealed that SNP rs2241715 is strongly associated with asthma under genotypic model. Conclusion: rs2241715 was found to be a genetic risk factor for asthma in Pakistani population.


Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004;59(5):469–78.

Lee YC, Cheon KT, Lee HB, Kim W, Rhee YK, Kim DS. Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma. Allergy 2000;55(10):959–63.

James AL, Elliot JG, Jones RL, Carroll ML, Mauad T, Bai TR, et al. Airway smooth muscle hypertrophy and hyperplasia in asthma. Am J Respir Crit Care Med 2012;185(10):1058–64.

Rogers DF. Airway mucus hypersecretion in asthma: an undervalued pathology? Curr Opin Pharmacol 2004;4(3):241–50.

WHO. The Global Asthma Report. [Internet]. 2014. [cited 2022 June]. Available from:

Ghani MU, Sabar MF, Shahid M, Awan FI, Akram M. A report on asthma genetics studies in Pakistani population. Adv Life Sci 2017;4(2):33–8.

Hasnain SM, Khan M, Saleem A, Waqar MA. Prevalence of asthma and allergic rhinitis among school children of Karachi, Pakistan, 2007. J Asthma 2009;46(1):86–90.

Ramasamy A, Kuokkanen M, Vedantam S, Gajdos ZK, Couto Alves A, Lyon HN, et al. Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. PLoS One 2012;7(9):e44008.

Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souef P, et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 2011;378(9795):1006–14.

Ullemar V, Magnusson PK, Lundholm C, Zettergren A, Melen E, Lichtenstein P, et al. Heritability and confirmation of genetic association studies for childhood asthma in twins. Allergy 2016;71(2):230–8.

Bonnelykke K, Sleiman P, Nielsen K, Kreiner-Moller E, Mercader JM, Belgrave D, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet 2014;46(1):51–5.

Galanter JM, Gignoux CR, Torgerson DG, Roth LA, Eng C, Oh SS, et al. Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study. J Allergy Clin Immunol 2014;134(2):295–305.

Sabar MF, Ghani MU, Shahid M, Sumrin A, Ali A, Akram M, et al. Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan. J Asthma 2016;53(4):341–8.

Sabar MF, Shahid M, Bano I, Ghani MU, Akram M, Iqbal F, et al. rs12603332 is associated with male asthma patients specifically in urban areas of Lahore, Pakistan. J Asthma 2017;54(9):887–92.

Ghani MU, Sabar MF, Bano I, Shahid M, Akram M, Khalid I, et al. Evaluation of ADAM33 gene’s single nucleotide polymorphism variants against asthma and the unique pattern of inheritance in Northern and Central Punjab, Pakistan. Saudi Med J 2019;40(8):774–80.

Meng JF, Rosenwasser LJ. Unraveling the genetic basis of asthma and allergic diseases. Allergy Asthma Immunol Res 2010;2(4):215–27.

Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T, et al. Latent TGF-beta structure and activation. Nature 2011;474(7351):343–9.

Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 2006;24:99–146.

Sagara H, Okada T, Okumura K, Ogawa H, Ra C, Fukuda T, et al. Activation of TGF-β/Smad2 signaling is associated with airway remodeling in asthma. J Allergy Clin Immunol 2002;110(2):249–54.

Le AV, Cho JY, Miller M, McElwain S, Golgotiu K, Broide DH. Inhibition of allergen-induced airway remodeling in Smad 3-deficient mice. J Immunol 2007;178(11):7310–6.

Chen JB, Zhang J, Hu HZ, Xue M, Jin YJ. Polymorphisms of TGFB1, TLE4 and MUC22 are associated with childhood asthma in Chinese population. Allergol Immunopathol (Madr) 2017;45(5):432–8.

Yang XX, Li FX, Wu YS, Wu D, Tan JY, Li M. Association of TGF-beta1, IL-4 and IL-13 gene polymerphisms with asthma in a Chinese population. Asian Pac J Allergy Immunol 2011;29(3):273–7.

Li H, Li Y, Zhang M, Xu G, Feng X, Xi J, et al. Associations of genetic variants in ADAM33 and TGF-beta1 genes with childhood asthma risk. Biomed Rep 2014;2(4):533–8.

Yucesoy B, Kashon ML, Johnson VJ, Lummus ZL, Fluharty K, Gautrin D, et al. Genetic variants in TNFalpha, TGFB1, PTGS1 and PTGS2 genes are associated with diisocyanate-induced asthma. J Immunotoxicol 2016;13(1):119–26.

Wu H, Romieu I, Shi M, Hancock DB, Li H, Sienra-Monge JJ, et al. Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans. J Allergy Clin Immunol 2010;125(2):321–7.e13.

Ghani MU, Sabar MF, Akram M. Smart approach for cost-effective genotyping of single nucleotide polymorphisms. Kuwait J Sci 2021;48(2):1–11.

Costa R, Marques C, Rios R, Silva H, Carneiro N, Cana Brasil T, et al. Are TGF-β gene polymorphisms associated with asthma risk? OA Immunol 2013;1:1–5.

Sabar MF, Akram M, Awan FI, Ghani MU, Shahid M, Iqbal Z, et al. Awareness of Asthma Genetics in Pakistan: A Review with Some Recommendations. Adv Life Sci 2018;6(1):1–10.

Salazar LA, Hirata MH, Cavalli SA, Machado MO, Hirata RD. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem 1998;44(8 Pt 1):1748–50.

Al-Alawi M, Hassan T, Chotirmall SH. Transforming growth factor beta and severe asthma: a perfect storm. Respir Med 2014;108(10):1409–23.

Yocum GT, Gaudet JG, Lee SS, Stern Y, Teverbaugh LA, Sciacca RR, et al. Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy. Stroke 2009;40(5):1597–603.

Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 1999;8(1):93–7.

Buckova D, Izakovicova Holla L, Benes P, Znojil V, Vacha J. TGF-beta1 gene polymorphisms. Allergy 2001;56(12):1236–7.

Zhang Y, Zhang J, Huang J, Li X, He C, Tian C, et al. Polymorphisms in the transforming growth factor-beta1 gene and the risk of asthma: A meta-analysis. Respirology 2010;15(4):643–50.