RISK LOCI FOR CHRONIC OBSTRUCTIVE DISEASE RESIDE ON CHROMOSOME 14: A CASE-CONTROL STUDY ON THE PAKISTANI POPULATION

Authors

  • Peerzada Fawad Ullah Jan
  • Samra Kousar Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
  • Atif Mahmood Fatima Memorial Hospital, FMH college of Medicine and Dentistry, Lahore, Pakistan
  • Sarooj Nadeem Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. 2-Genomics Research Centre, Academia Sinica, Taiwan
  • Kausar Malik Centre of Excellence in molecular Biology, University of the Punjab, Lahore, Pakistan
  • Waqas Safir 1-Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan,2-Department of Biochemistry, Hazara University, Mansehra, Pakistan.
  • Nodia Shujaat Department of Biochemistry, Hazara University, Mansehra, Pakistan.
  • Fahim Ullah Khan Department of Agriculture, Hazara University, Mansehra, Pakistan
  • Mariam Shahid Centre of Excellence in Molecular Biology, University of the Punjab

DOI:

https://doi.org/10.55519/JAMC-02-11430

Keywords:

COPD, SERPINA, Single Nucleotide Polymorphism, Association Study

Abstract

Background: Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide, is characterized by airflow limitation that can be due to abnormalities in the airway and/or alveoli. Genetic diagnosis at an early stage can be a key factor in the provision of accurate and timely treatment. Single Nucleotide polymorphisms (SNPs) are an important tool to study genetic association/ predisposition of the disease and have great potential to be diagnostic markers for early diagnosis of disease. Methods: This case-control COPD association study was designed for the five SNPs residing on potential candidate genes (SERPINA1, SERPINA3, RIN3), to check whether these genes are involved in the genetic predisposition for COPD in the Pakistani population or not. The SNAPshot method was used to find out the risk alleles and haplotypes using ABI Genetic analyzer 3130. GeneMapper, Haploview and PLINK 1.9 software were used for analyzing the genotypes and haplotypes taking smoking exposure and gender as covariates. Results: Two of the SNPs, rs4934 and rs17473 were found to be independently and significantly associated with COPD in our studied population whereas haplotype H1 for two SNPs, rs754388 and rs17473 (that are in high linkage disequilibrium), was found to be a significant risk factor for developing COPD symptoms. Conclusion: SNP variants of SERPINA1 and SERPINA3 are significantly and independently associated with COPD in the local population of Pakistan.

Author Biographies

Peerzada Fawad Ullah Jan

M.Phil student

1-Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.

2-Department of Biochemistry, Hazara University, Mansehra, Pakistan.

Samra Kousar, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

Ph.D student

Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

Atif Mahmood, Fatima Memorial Hospital, FMH college of Medicine and Dentistry, Lahore, Pakistan

Professor/Head of Pulmonology

Fatima Memorial Hospital, FMH college of Medicine and Dentistry, Lahore, Pakistan

 

Sarooj Nadeem, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. 2-Genomics Research Centre, Academia Sinica, Taiwan

1-MPhil Student

Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.

2-Research affiliate

Genomics Research Centre, Academia Sinica, Taiwan

Kausar Malik, Centre of Excellence in molecular Biology, University of the Punjab, Lahore, Pakistan

Director/Professor

Centre of Excellence in molecular Biology, University of the Punjab, Lahore, Pakistan

Waqas Safir, 1-Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan,2-Department of Biochemistry, Hazara University, Mansehra, Pakistan.

M.Phil Student

1-Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

2-Department of Biochemistry, Hazara University, Mansehra, Pakistan.

 

Nodia Shujaat, Department of Biochemistry, Hazara University, Mansehra, Pakistan.

Head of Department

Department of Biochemistry, Hazara University, Mansehra, Pakistan.

Fahim Ullah Khan, Department of Agriculture, Hazara University, Mansehra, Pakistan

Assistant Professor

Department of Agriculture, Hazara University, Mansehra, Pakistan

Mariam Shahid, Centre of Excellence in Molecular Biology, University of the Punjab

Assistant professor

Incharge Genetic Screening Lab

Centre of Excellence in Molecular Biology, University of the Punjab, Lahore

References

Adeloye D, Song P, Zhu Y, Campbell H, Sheikh A, Rudan I, et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med 2022;10(5):447-58.

WHO. Projection of mortality and Causes of death, 2016 and 2060. [Internet]. [cited 2022 Aug 20]. Available from: https://www.who.int/healthinfo/global_burden_disease/projections

Singh D, Agusti A, Martinez FJ, Papi A, Pavord ID, Wedzicha JA, et al. Blood Eosinophils and Chronic Obstructive Pulmonary Disease: A Global Initiative for Chronic Obstructive Lung Disease Science Committee 2022 Review. Am J Respir Crit Care Med 2022;206(1):17-24.

Tageldin MA, Nafti S, Khan JA, Nejjari C, Beji M, Mahboub B, et al. Distribution of COPD-related symptoms in the Middle East and North Africa: results of the BREATHE study. Respir Med 2012;106:S25-32.

Razzaq S, Nafees AA, Irfan M, Fatmi Z. Prevalence and Risk Factors of COPD in Karachi, Pakistan: Findings from the Adult Asthma Study-Karachi. In: ISEE Conference Abstracts; 2018.

Sultana T, Afzal A, Sultana S, Al-Ghanim K, Shahid T, Jabeen Z, et al. Epidemiological estimates of Respiratory diseases in the hospital population, Faisalabad, Pakistan. Braz Arch Biol Technol 2017;60:e17160358.

Nafees AA, Fatmi Z, Kadir MM, Sathiakumar N. Chronic bronchitis and chronic obstructive pulmonary disease (COPD) among textile workers in Karachi, Pakistan. J Coll Physicians Surg Pak 2016;26(5):384-9.

Di Stefano A, Ricciardolo FL, Caramori G, Adcock IM, Chung KF, Barnes PJ, et al. Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression. Eur Respir J 2017;49(5):1602006.

Russo AJ, Neville L, Wroge C. Low serum alpha-1 antitrypsin (AAT) in family members of individuals with autism correlates with PiMZ genotype. Biomark Insights 2009;4:45-56.

Owen MC, Brennan SO, Lewis JH, Carrell RW. Mutation of antitrypsin to antithrombin: α1-antitrypsin Pittsburgh (358 Met†’ Arg), a fatal bleeding disorder. N Engl J Med 1983;309(12):694-8.

Henao MP, Craig TJ. Understanding alpha-1 antitrypsin deficiency: A review with an allergist's outlook. Allergy Asthma Proc 2017;38(2):98-107.

Stockley RA. Neutrophils and the pathogenesis of COPD. Chest 2002;121(5 Suppl):S151-5.

Turner AM. Fifty years on: GWAS confirms the role of a rare variant in lung disease. PLoS Genet 2013;9(8):e1003768.

Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 1992;357(6379):605-7.

Sandford A, Silverman E. Chronic obstructive pulmonary disease. 1: Susceptibility factors for COPD the genotype-environment interaction. Thorax 2002;57(8):736-41.

Cox DW, Levison H. Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes). Am Rev Respir Dis 1988;137(2):371-5.

NLM. Alpha-1 antitrypsin deficiency. [Internet]. MedlinePlus Trusted Health Information for you 2017. [cited 2017 June 20]. Available from: https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency

Bashir A, Shah NN, Hazari YM, Habib M, Bashir S, Hilal N, et al. Novel variants of SERPIN1A gene: interplay between alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease. Respir Med 2016;117:139-49.

Thun GA, Imboden M, Ferrarotti I, Kumar A, Obeidat Me, Zorzetto M, et al. Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels. PLoS Genet 2013;9(8):e1003585.

Cho MH, Castaldi PJ, Hersh CP, Hobbs BD, Barr RG, Tal-Singer R, et al. A genome-wide association study of emphysema and airway quantitative imaging phenotypes. Am J Respir Crit Care Med 2015;192(5):559-69.

de Serres FJ. Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed. Environ Health Perspect 2003;111(16):1851-4.

Blanco I, Bueno P, Diego I, Pérez-Holanda S, Casas-Maldonado F, Esquinas C, et al. Alpha-1 antitrypsin Pi* Z gene frequency and Pi* ZZ genotype numbers worldwide: an update. Int J Chron Obstruct Pulmon Dis 2017;12:561.

Blanco I, Bueno P, Diego I, Pérez-Holanda S, Lara B, Casas-Maldonado F, et al. Alpha-1 antitrypsin Pi* SZ genotype: estimated prevalence and number of SZ subjects worldwide. Int J Chron Obstruct Pulmon Dis 2017;12:1683-94.

Kajiho H, Saito K, Tsujita K, Kontani K, Araki Y, Kurosu H, et al. RIN3: a novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway. J Cell Sci 2003;116(20):4159-68.

Cho MH, McDonald MLN, Zhou X, Mattheisen M, Castaldi PJ, Hersh CP, et al. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Lancet Respir Med 2014;2(3):214-25.

Li X, Ortega VE, Ampleford EJ, Barr RG, Christenson SA, Cooper CB, et al. Genome-wide association study of lung function and clinical implication in heavy smokers. BMC Med Genet 2018;19(1):134.

Ward LD, Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res 2016;44(D1):D877-81.

Suzuki M, Betsuyaku T, Ito Y, Nagai K, Nasuhara Y, Kaga K, et al. Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2008;39(6):673-82.

Camiciottoli G, Cavigli E, Grassi L, Diciotti S, Orlandi I, Zappa M, et al. Prevalence and correlates of pulmonary emphysema in smokers and former smokers. A densitometric study of participants in the ITALUNG trial. Eur Radiol 2009;19(1):58-66.

Sverzellati N, Calabrò E, Randi G, La Vecchia C, Marchianò A, Kuhnigk JM, et al. Sex differences in emphysema phenotype in smokers without airflow obstruction. Eur Respir J 2009;33(6):1320-8.

Zhao K, Dong R, Yu Y, Tu C, Li Y, Cui Y, et al. Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT/NF-κB pathway. Aging (Albany NY) 2020;12(10):9125-38.

Uniyal S, Dhasmana A, Tyagi A, Muyal JP. ATRA reduces inflammation and improves alveolar epithelium regeneration in emphysematous rat lung. Biomed Pharmacother 2018;108:1435-50.

Yew-Booth L, Birrell MA, Lau MS, Baker K, Jones V, Kilty I, et al. JAK-STAT pathway activation in COPD. Eur Respir J 2015;46(3):843-5.

Huan W, Tianzhu Z, Yu L, Shumin W. Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway. Inflammation 2017;40(3):884-93.

Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M, et al. GeneCards Version 3: the human gene integrator. Database (Oxford) 2010;2010:baq020.

Hopkins RJ, Young RP, Hay B, Gamble GD. B44 COPD: GENETICS: Genetic Susceptibility To Lung Cancer And COPD In Chronic Smokers: The Possible Role Of Rin3 And Tgfb2. Am J Respir Crit Care Med 2014;189:1.

Shen R, Murphy CJ, Xu X, Hu M, Ding J, Wu C. Ras and Rab Interactor 3: From Cellular Mechanisms to Human Diseases. Front Cell Dev Biol 2022;10:824961.

Downloads

Published

2023-04-16

How to Cite

Jan, P. F. U., Kousar, S., Mahmood, A., Nadeem, S., Malik, K., Safir, W., … Shahid, M. (2023). RISK LOCI FOR CHRONIC OBSTRUCTIVE DISEASE RESIDE ON CHROMOSOME 14: A CASE-CONTROL STUDY ON THE PAKISTANI POPULATION. Journal of Ayub Medical College Abbottabad, 35(2). https://doi.org/10.55519/JAMC-02-11430

Similar Articles

1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.