STAT6 variants and non-atopic asthma in Pakistani population

Ayesha Riaz; Muhammad Ahsan Riaz; Luqman Khan; Muhammad Shareef Masoud; Ghulam Hussain; Muhammad Iqbal; Muhammad Qasim

doi:10.14715/cmb/2018.64.14.3

Issue

Vol. 64 No. 14: Issue 14

Issue Published : December 3, 2018

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

STAT6 variants and non-atopic asthma in Pakistani population

https://doi.org/10.14715/cmb/2018.64.14.3

Ayesha Riaz

Department of Zoology, Government College Women University Faisalabad, Pakistan

Muhammad Ahsan Riaz

Department of Environmental Sciences and Engineering, Government College University Faisalabad, Pakistan

Luqman Khan

Graduate School of Life Sciences, Tohoku University, Sendai, Japan

Muhammad Shareef Masoud

Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Pakistan

Ghulam Hussain

Department of Physiology, Government College University Faisalabad, Pakistan

Muhammad Iqbal

Pakistan Council of Scientific and Industrial Research (PCSIR) Islamabad. Pakistan

Muhammad Qasim

Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Pakistan

Corresponding Author(s) : Ayesha Riaz

ayeshariazrana@gmail.com

Cellular and Molecular Biology, Vol. 64 No. 14: Issue 14
Article Published : November 30, 2018

Abstract

Asthma a chronic airway inflammatory disease mainly characterized by airways obstruction. Airway hyper responsiveness particularly in eosinophils and inflammatory mediators affect the bronchial mucosa. Genetic association studies show the association of single nucleotide polymorphisms (SNPs) in the STAT6 gene with asthma risk. Role of Signal transducer and activator of transcription 6 (STAT6) is acute for T-helper 2 (Th2) mediated responses during allergic airway diseases. Objective was to investigate whether the two single nucleotide polymorphism (rs4559 and rs324011) in STAT6 gene are associated with non-atopic asthma risk in Pakistani population. One hundred (100) asthma patients with a positive family history with at least one-ï¬rst degree asthma affected relative were enrolled. Normal healthy individuals (n=100) were also included as control subjects in the current study. STAT6 SNPs rs4559 and rs324011 were genotyped using SNaPSHOT mini-sequencing assay and the obtained data was statistically analyzed by online SHEsis software. A case-control study for association of STAT6 polymorphisms rs4559 and rs324011 with asthma risk was performed. The SNP rs4559 was found statistically significantly associated with increased susceptibility of developing non-atopic asthma in Pakistani individuals. The SNP rs324011 polymorphism in intron 2 of STAT6 gene may be associated with increased susceptibility of the development of non-atopic asthma as a strong statistically significant difference in allele frequency and genotype was observed between asthmatics and controls showing association with non-atopic asthma in Pakistani individuals. rs4559 and rs324011SNPs in STAT6 found associated with non-atopic asthma risk. We observed the statistically significant association between STAT6 polymorphisms with intrinsic (non-atopic) asthma in Pakistani population.

Keywords

Asthma STAT6 Minisequencing Gene polymorphism SNPs.

Riaz, A., Ahsan Riaz, M., Khan, L., Shareef Masoud, M., Hussain, G., Iqbal, M., & Qasim, M. (2018). STAT6 variants and non-atopic asthma in Pakistani population. Cellular and Molecular Biology, 64(14), 15–18. https://doi.org/10.14715/cmb/2018.64.14.3

Download Citation

References

Acevedo, N., Bornacelly, A., Mercado, D., Unneberg, P., Mittermann, I., Valenta, R., Kennedy, M., Scheynius, A., Caraballo, L., 2016. Genetic Variants in CHIA and CHI3L1 Are Associated with the IgE Response to the Ascaris Resistance Marker ABA-1 and the Birch Pollen Allergen Bet v 1. PloS one 11, e0167453.
Al-Muhsen, S., Vazquez-Tello, A., Jamhawi, A., Al-Jahdali, H., Bahammam, A., Al Saadi, M., Iqbal, S.M., Alfrayh, A., Afzal, S., Al-Khamis, N., 2014. Association of the STAT-6 rs324011 (C2892T) variant but not rs324015 (G2964A), with atopic asthma in a Saudi Arabian population. Human immunology 75, 791-795.
Amin, K., 2015. Allergic respiratory inflammation and remodeling. Turkish Thoracic Journal 16, 133-140.
Asher, M., Keil, U., Anderson, H., Beasley, R., Crane, J., Martinez, F., Mitchell, E., Pearce, N., Sibbald, B., Stewart, A., 1995. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. European respiratory journal 8, 483-491.
Berce, V., PotoË‡nik, U., 2010. Association of Q551R polymorphism in the interleukin 4 receptor gene with nonatopic asthma in Slovenian children. Wiener klinische Wochenschrift 122, 11-18.
Broide, D.H., 2001. Molecular and cellular mechanisms of allergic disease. Journal of Allergy and Clinical Immunology 108, S65-S71.
Busse, W.W., 2001. Asthma. N. Engl. J. Med. 344, 350.
Cazzola, M., Skoda, R.C., 2000. Translational pathophysiology: a novel molecular mechanism of human disease. Blood 95, 3280-3288.
Christodoulopoulos, P., Cameron, L., Nakamura, Y., Lemière, C., Muro, S., Dugas, M., Boulet, L.-P., Laviolette, M., Olivenstein, R., Hamid, Q., 2001. TH2 cytokine–associated transcription factors in atopic and nonatopic asthma: Evidence for differential signal transducer and activator of transcription 6 expression. Journal of allergy and clinical immunology 107, 586-591.
D'Amato, G., Holgate, S.T., Pawankar, R., Ledford, D.K., Cecchi, L., Al-Ahmad, M., Al-Enezi, F., Al-Muhsen, S., Ansotegui, I., Baena-Cagnani, C.E., 2015. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization. World Allergy Organization Journal 8, 1.
Duetsch, G., Illig, T., Loesgen, S., Rohde, K., Klopp, N., Herbon, N., Gohlke, H., Altmueller, J., Wjst, M., 2002. STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study. Human molecular genetics 11, 613-621.
Foster, P.S., Maltby, S., Rosenberg, H.F., Tay, H.L., Hogan, S.P., Collison, A.M., Yang, M., Kaiko, G.E., Hansbro, P.M., Kumar, R.K., 2017. Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunological reviews 278, 20-40.
Godava, M., Kopriva, F., Bohmova, J., Vodicka, R., Dusek, L., Cvanova, M., Muzik, J., Markova, M., Schneiderova, E., Vrtel, R., 2012. Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma bronchiale and IgE level and its possible epigenetic background. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc 156.
Granada, M., Wilk, J.B., Tuzova, M., Strachan, D.P., Weidinger, S., Albrecht, E., Gieger, C., Heinrich, J., Himes, B.E., Hunninghake, G.M., 2012. A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. Journal of Allergy and Clinical Immunology 129, 840-845. e821.
Kankaanpää, P., Nurmela, K., Erkkilä, A., Kalliomäki, M., Holmberg"Marttila, D., Salminen, S., Isolauri, E., 2001. Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy. Allergy 56, 633-638.
Lambrecht, B.N., Hammad, H., 2015. The immunology of asthma. Nat. Immunol. 16, 45.
Lee, N.A., Gelfand, E.W., Lee, J.J., 2001. Pulmonary T cells and eosinophils: coconspirators or independent triggers of allergic respiratory pathology? Journal of Allergy and Clinical Immunology 107, 945-957.
Li, Y., Wu, B., Xiong, H., Zhu, C., Zhang, L., 2007. Polymorphisms of STAT-6, STAT-4 and IFN-Î³ genes and the risk of asthma in Chinese population. Respiratory medicine 101, 1977-1981.
Lu, W., Zhang, C., Yi, Z., Li, Z., Wu, Z., Fang, Y., 2012. Association between BDNF Val66Met polymorphism and cognitive performance in antipsychotic-naive patients with schizophrenia. J. Mol. Neurosci. 47, 505-510.
Martinez, F.D., Holt, P.G., 1999. Role of microbial burden in aetiology of allergy and asthma. The Lancet 354, SII12-SII15.
Miller, R.L., Eppinger, T.M., McConnell, D., Cunningham-Rundles, C., Rothman, P., 1998. Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E. Journal of allergy and clinical immunology 102, 503-511.
Palmer, L.J., Cookson, W.O., 2000. Genomic approaches to understanding asthma. Genome research 10, 1280-1287.
Patel, B.K., Keck, C.L., O'Leary, R.S., Popescu, N.C., LaRochelle, W.J., 1998. Localization of the human stat6 gene to chromosome 12q13. 3–q14. 1, a region implicated in multiple solid tumors. Genomics 52, 192-200.
Qian, X., Gao, Y., Ye, X., Lu, M., 2014. Association of STAT6 variants with asthma risk: a systematic review and meta-analysis. Human immunology 75, 847-853.
Schedel, M., Carr, D., Klopp, N., Woitsch, B., Illig, T., Stachel, D., Schmid, I., Fritzsch, C., Weiland, S.K., von Mutius, E., 2004. A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels. Journal of allergy and clinical immunology 114, 1100-1105.
Shirakawa, T., Enomoto, T., Shimazu, S.-i., Hopkin, J.M., 1997. The inverse association between tuberculin responses and atopic disorder. Science 275, 77-79.
Strina, A., Barreto, M.L., Cooper, P.J., Rodrigues, L.C., 2014. Risk factors for non-atopic asthma/wheeze in children and adolescents: a systematic review. Emerging themes in epidemiology 11, 5.
Weidinger, S., Klopp, N., Wagenpfeil, S., Rümmler, L., Schedel, M., Kabesch, M., Schäfer, T., Darsow, U., Jakob, T., Behrendt, H., 2004. Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults. Journal of medical genetics 41, 658-663.
Weiland, S., Björkstén, B., Brunekreef, B., Cookson, W., Von Mutius, E., Strachan, D., 2004. Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods. European Respiratory Journal 24, 406-412.
Zhou, J., Li, Y., Sun, D., 2017. Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China. Dermatology 233, 30-36.
Zhu, L., Zhu, Q., Zhang, X., Wang, H., 2013. The correlation analysis of two common polymorphisms in STAT6 gene and the risk of asthma: a meta-analysis. PloS one 8, e67657.
Zimmermann, N., Mishra, A., King, N.E., Fulkerson, P.C., Doepker, M.P., Nikolaidis, N.M., Kindinger, L.E., Moulton, E.A., Aronow, B.J., Rothenberg, M.E., 2004. Transcript signatures in experimental asthma: identification of STAT6-dependent and-independent pathways. The Journal of Immunology 172, 1815-1824.

References

Acevedo, N., Bornacelly, A., Mercado, D., Unneberg, P., Mittermann, I., Valenta, R., Kennedy, M., Scheynius, A., Caraballo, L., 2016. Genetic Variants in CHIA and CHI3L1 Are Associated with the IgE Response to the Ascaris Resistance Marker ABA-1 and the Birch Pollen Allergen Bet v 1. PloS one 11, e0167453.

Al-Muhsen, S., Vazquez-Tello, A., Jamhawi, A., Al-Jahdali, H., Bahammam, A., Al Saadi, M., Iqbal, S.M., Alfrayh, A., Afzal, S., Al-Khamis, N., 2014. Association of the STAT-6 rs324011 (C2892T) variant but not rs324015 (G2964A), with atopic asthma in a Saudi Arabian population. Human immunology 75, 791-795.

Amin, K., 2015. Allergic respiratory inflammation and remodeling. Turkish Thoracic Journal 16, 133-140.

Asher, M., Keil, U., Anderson, H., Beasley, R., Crane, J., Martinez, F., Mitchell, E., Pearce, N., Sibbald, B., Stewart, A., 1995. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. European respiratory journal 8, 483-491.

Berce, V., PotoË‡nik, U., 2010. Association of Q551R polymorphism in the interleukin 4 receptor gene with nonatopic asthma in Slovenian children. Wiener klinische Wochenschrift 122, 11-18.

Broide, D.H., 2001. Molecular and cellular mechanisms of allergic disease. Journal of Allergy and Clinical Immunology 108, S65-S71.

Busse, W.W., 2001. Asthma. N. Engl. J. Med. 344, 350.

Cazzola, M., Skoda, R.C., 2000. Translational pathophysiology: a novel molecular mechanism of human disease. Blood 95, 3280-3288.

Christodoulopoulos, P., Cameron, L., Nakamura, Y., Lemière, C., Muro, S., Dugas, M., Boulet, L.-P., Laviolette, M., Olivenstein, R., Hamid, Q., 2001. TH2 cytokine–associated transcription factors in atopic and nonatopic asthma: Evidence for differential signal transducer and activator of transcription 6 expression. Journal of allergy and clinical immunology 107, 586-591.

D'Amato, G., Holgate, S.T., Pawankar, R., Ledford, D.K., Cecchi, L., Al-Ahmad, M., Al-Enezi, F., Al-Muhsen, S., Ansotegui, I., Baena-Cagnani, C.E., 2015. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization. World Allergy Organization Journal 8, 1.

Duetsch, G., Illig, T., Loesgen, S., Rohde, K., Klopp, N., Herbon, N., Gohlke, H., Altmueller, J., Wjst, M., 2002. STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study. Human molecular genetics 11, 613-621.

Foster, P.S., Maltby, S., Rosenberg, H.F., Tay, H.L., Hogan, S.P., Collison, A.M., Yang, M., Kaiko, G.E., Hansbro, P.M., Kumar, R.K., 2017. Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunological reviews 278, 20-40.

Godava, M., Kopriva, F., Bohmova, J., Vodicka, R., Dusek, L., Cvanova, M., Muzik, J., Markova, M., Schneiderova, E., Vrtel, R., 2012. Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma bronchiale and IgE level and its possible epigenetic background. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc 156.

Granada, M., Wilk, J.B., Tuzova, M., Strachan, D.P., Weidinger, S., Albrecht, E., Gieger, C., Heinrich, J., Himes, B.E., Hunninghake, G.M., 2012. A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. Journal of Allergy and Clinical Immunology 129, 840-845. e821.

Kankaanpää, P., Nurmela, K., Erkkilä, A., Kalliomäki, M., Holmberg"Marttila, D., Salminen, S., Isolauri, E., 2001. Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy. Allergy 56, 633-638.

Lambrecht, B.N., Hammad, H., 2015. The immunology of asthma. Nat. Immunol. 16, 45.

Lee, N.A., Gelfand, E.W., Lee, J.J., 2001. Pulmonary T cells and eosinophils: coconspirators or independent triggers of allergic respiratory pathology? Journal of Allergy and Clinical Immunology 107, 945-957.

Li, Y., Wu, B., Xiong, H., Zhu, C., Zhang, L., 2007. Polymorphisms of STAT-6, STAT-4 and IFN-Î³ genes and the risk of asthma in Chinese population. Respiratory medicine 101, 1977-1981.

Lu, W., Zhang, C., Yi, Z., Li, Z., Wu, Z., Fang, Y., 2012. Association between BDNF Val66Met polymorphism and cognitive performance in antipsychotic-naive patients with schizophrenia. J. Mol. Neurosci. 47, 505-510.

Martinez, F.D., Holt, P.G., 1999. Role of microbial burden in aetiology of allergy and asthma. The Lancet 354, SII12-SII15.

Miller, R.L., Eppinger, T.M., McConnell, D., Cunningham-Rundles, C., Rothman, P., 1998. Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E. Journal of allergy and clinical immunology 102, 503-511.

Palmer, L.J., Cookson, W.O., 2000. Genomic approaches to understanding asthma. Genome research 10, 1280-1287.

Patel, B.K., Keck, C.L., O'Leary, R.S., Popescu, N.C., LaRochelle, W.J., 1998. Localization of the human stat6 gene to chromosome 12q13. 3–q14. 1, a region implicated in multiple solid tumors. Genomics 52, 192-200.

Qian, X., Gao, Y., Ye, X., Lu, M., 2014. Association of STAT6 variants with asthma risk: a systematic review and meta-analysis. Human immunology 75, 847-853.

Schedel, M., Carr, D., Klopp, N., Woitsch, B., Illig, T., Stachel, D., Schmid, I., Fritzsch, C., Weiland, S.K., von Mutius, E., 2004. A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels. Journal of allergy and clinical immunology 114, 1100-1105.

Shirakawa, T., Enomoto, T., Shimazu, S.-i., Hopkin, J.M., 1997. The inverse association between tuberculin responses and atopic disorder. Science 275, 77-79.

Strina, A., Barreto, M.L., Cooper, P.J., Rodrigues, L.C., 2014. Risk factors for non-atopic asthma/wheeze in children and adolescents: a systematic review. Emerging themes in epidemiology 11, 5.

Weidinger, S., Klopp, N., Wagenpfeil, S., Rümmler, L., Schedel, M., Kabesch, M., Schäfer, T., Darsow, U., Jakob, T., Behrendt, H., 2004. Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults. Journal of medical genetics 41, 658-663.

Weiland, S., Björkstén, B., Brunekreef, B., Cookson, W., Von Mutius, E., Strachan, D., 2004. Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods. European Respiratory Journal 24, 406-412.

Zhou, J., Li, Y., Sun, D., 2017. Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China. Dermatology 233, 30-36.

Zhu, L., Zhu, Q., Zhang, X., Wang, H., 2013. The correlation analysis of two common polymorphisms in STAT6 gene and the risk of asthma: a meta-analysis. PloS one 8, e67657.

Zimmermann, N., Mishra, A., King, N.E., Fulkerson, P.C., Doepker, M.P., Nikolaidis, N.M., Kindinger, L.E., Moulton, E.A., Aronow, B.J., Rothenberg, M.E., 2004. Transcript signatures in experimental asthma: identification of STAT6-dependent and-independent pathways. The Journal of Immunology 172, 1815-1824.

Author biographies is not available.