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BioMed Research International
Volume 2014, Article ID 708903, 17 pages
http://dx.doi.org/10.1155/2014/708903
Research Article

Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

1Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
2Department of Pediatrics, Kursk State Medical University, 11a Koltsov Street, Kursk 305035, Russia
3Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, 10 Nabereznaya Ushaiki Tomsk 634050, Russia
4Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany
5Hanover Unified Biobank, Hanover Medical School, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany

Received 23 February 2014; Revised 5 April 2014; Accepted 7 April 2014; Published 5 May 2014

Academic Editor: Siyuan Zheng

Copyright © 2014 Alexey V. Polonikov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. National Asthma Education and Prevention Program (NAEPP) , Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, National Heart Lung and Blood Institute, Bethesda, Md, USA, 2007.
  2. C. Ober and T.-C. Yao, “The genetics of asthma and allergic disease: a 21st century perspective,” Immunological Reviews, vol. 242, no. 1, pp. 10–30, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. Y. Zhang, M. F. Moffatt, and W. O. C. Cookson, “Genetic and genomic approaches to asthma: new insights for the origins,” Current Opinion in Pulmonary Medicine, vol. 18, no. 1, pp. 6–13, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. M. F. Moffatt, I. G. Gut, F. Demenais et al., “A large-scale, consortium-based genomewide association study of asthma,” The New England Journal of Medicine, vol. 363, no. 13, pp. 1211–1221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. D. G. Torgerson, E. J. Ampleford, G. Y. Chiu et al., “Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations,” Nature Genetics, vol. 43, no. 9, pp. 887–892, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. T. A. Pearson and T. A. Manolio, “How to interpret a genome-wide association study,” Journal of the American Medical Association, vol. 299, no. 11, pp. 1335–1344, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. E. Evangelou and J. P. Ioannidis, “Meta-analysis methods for genome-wide association studies and beyond,” Nature Reviews Genetics, vol. 14, no. 6, pp. 379–389, 2013. View at Publisher · View at Google Scholar
  8. E. E. Eichler, J. Flint, G. Gibson et al., “Missing heritability and strategies for finding the underlying causes of complex disease,” Nature Reviews Genetics, vol. 11, no. 6, pp. 446–450, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. S. A. Tishkoff and B. C. Verrelli, “Patterns of human genetic diversity: implications for human evolutionary history and disease,” Annual Review of Genomics and Human Genetics, vol. 4, pp. 293–340, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Y. Kim, R. H. Dekruyff, and D. T. Umetsu, “The many paths to asthma: phenotype shaped by innate and adaptive immunity,” Nature Immunology, vol. 11, no. 7, pp. 577–584, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. D. T. Swarr and H. Hakonarson, “Unraveling the complex genetic underpinnings of asthma and allergic disorders,” Current Opinion in Allergy and Clinical Immunology, vol. 10, no. 5, pp. 434–442, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. N. C. Battle, S. Choudhry, H.-J. Tsai et al., “Ethnicity-specific gene-gene interaction between IL-13 and IL-4Rα among African Americans with asthma,” American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 9, pp. 881–887, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. H. J. Cordell, “Detecting gene-gene interactions that underlie human diseases,” Nature Reviews Genetics, vol. 10, no. 6, pp. 392–404, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Hoh, A. Wille, and J. Ott, “Trimming, weighting, and grouping SNPs in human case-control association studies,” Genome Research, vol. 11, no. 12, pp. 2115–2119, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. M. D. Ritchie, L. W. Hahn, N. Roodi et al., “Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer,” American Journal of Human Genetics, vol. 69, no. 1, pp. 138–147, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Millstein, D. V. Conti, F. D. Gilliland, and W. J. Gauderman, “A testing framework for identifying susceptibility genes in the presence of epistasis,” American Journal of Human Genetics, vol. 78, no. 1, pp. 15–27, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. A. A. Motsinger and M. D. Ritchie, “Multifactor dimensionality reduction: an analysis strategy for modelling and detecting gene-gene interactions in human genetics and pharmacogenomics studies,” Human Genomics, vol. 2, no. 5, pp. 318–328, 2006. View at Google Scholar · View at Scopus
  18. T. J. Jorgensen, I. Ruczinski, B. Kessing, M. W. Smith, Y. Y. Shugart, and A. J. Alberg, “Hypothesis-driven candidate gene association studies: practical design and analytical considerations,” American Journal of Epidemiology, vol. 170, no. 8, pp. 986–993, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. A. V. Polonikov, V. P. Ivanov, and M. A. Solodilova, “Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of bronchial asthma: the importance of gene-gene and gene-environment interactions for disease susceptibility,” Journal of Human Genetics, vol. 54, no. 8, pp. 440–449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. J. London, “Gene-air pollution interactions in asthma,” Proceedings of the American Thoracic Society, vol. 4, no. 3, pp. 217–220, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. F. Castro-Giner, N. Künzli, B. Jacquemin et al., “Traffic-related air pollution, oxidative stress genes, and asthma (ECHRS),” Environmental Health Perspectives, vol. 117, no. 12, pp. 1919–1924, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. J. C. Mak and M. M. Chan-Yeung, “Reactive oxidant species in asthma,” Current Opinion in Pulmonary Medicine, vol. 12, no. 1, pp. 7–11, 2006. View at Publisher · View at Google Scholar
  23. H. Sugiura and M. Ichinose, “Oxidative and nitrative stress in bronchial asthma,” Antioxidants and Redox Signaling, vol. 10, no. 4, pp. 785–797, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. M. A. Riedl and A. E. Nel, “Importance of oxidative stress in the pathogenesis and treatment of asthma,” Current Opinion in Allergy and Clinical Immunology, vol. 8, no. 1, pp. 49–56, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. A. V. Polonikov, V. P. Ivanov, M. A. Solodilova, I. V. Khoroshaya, M. A. Kozhuhov, and V. I. Panfilov, “The relationship between polymorphisms in the glutamate cysteine ligase gene and asthma susceptibility,” Respiratory Medicine, vol. 101, no. 11, pp. 2422–2424, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. M. A. Solodilova, V. P. Ivanov, A. V. Polonikov, I. V. Khoroshaya, M. A. Kozhukhov, and V. I. Panfilov, “Heterozygosity of 198LEU mutant allele in glutathione peroxidase-1 gene as a risk factor of bronchial asthma associated with smoking,” Terapevticheskii Arkhiv, vol. 79, no. 3, pp. 33–36, 2007. View at Google Scholar · View at Scopus
  27. A. V. Polonikov, V. P. Ivanov, M. A. Solodilova, M. A. Kozhuhov, and V. I. Panfilov, “Tobacco smoking, fruit and vegetable intake modify association between −21A > T polymorphism of catalase gene and risk of bronchial asthma,” Journal of Asthma, vol. 46, no. 3, pp. 217–224, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. A. V. Polonikov, M. A. Solodilova, and V. P. Ivanov, “Genetic variation of myeloperoxidase gene contributes to atopic asthma susceptibility: a preliminary association study in russian population,” Journal of Asthma, vol. 46, no. 5, pp. 523–528, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. V. P. Ivanov, M. A. Solodilova, A. V. Polonikov, I. V. Khoroshaia, M. A. Kozhukhov, and V. I. Panfilov, “Association of C242T and A640G polymorphisms in the gene for p22phox subunit of NADPH oxidase with the risk of bronchial asthma: a pilot study,” Genetika, vol. 44, no. 5, pp. 693–701, 2008. View at Google Scholar · View at Scopus
  30. A. V. Polonikov, V. P. Ivanov, M. A. Solodilova, M. A. Kozhukhov, V. I. Panfilov, and I. V. Bulgakova, “Polymorphism −930A > G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma,” Terapevticheskiǐ Arkhiv, vol. 81, no. 3, pp. 31–35, 2009. View at Google Scholar · View at Scopus
  31. A. V. Polonikov, M. A. Solodilova, V. P. Ivanov et al., “Association study of the role of polymorphic variants of gene of NAD(P)H: quinone oxidoreductase type 1 in predisposition to bronchial asthma in population of Russians from the Central Chernozem region,” Journal of Medical Genetics (Moscow), vol. 10, no. 4, pp. 23–27, 2011. View at Google Scholar
  32. A. V. Polonikov, V. P. Ivanov, M. A. Solodilova, I. V. Khoroshaya, M. A. Kozhuhov, and V. I. Panfilov, “Promoter polymorphism G-50T of a human CYP2J2 epoxygenase gene is associated with common susceptibility to asthma,” Chest, vol. 132, no. 1, pp. 120–126, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. D. N. Cooper, R. L. Nussbaum, and M. Krawczak, “Proposed guidelines for papers describing DNA polymorphism-disease associations,” Human Genetics, vol. 110, no. 3, pp. 207–208, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. M. B. Freidin, V. P. Puzyrev, L. M. L. Ogorodova et al., “Analysis of the association between the T113M polymorphism of the human interleukin 9 gene and bronchial asthma,” Genetika, vol. 36, no. 4, pp. 559–561, 2000. View at Google Scholar · View at Scopus
  35. M. B. Freidin, V. P. Puzyrev, L. M. Ogorodova, O. S. Kobvakova, and I. M. Kulmanakova, “Polymorphism of the interleukin- and interleukin receptor genes: population distribution and association with atopic asthma,” Genetika, vol. 38, no. 12, pp. 1710–1718, 2002. View at Google Scholar · View at Scopus
  36. M. B. Freidin, O. S. Kobyakova, L. M. Ogorodova, and V. P. Puzyrev, “Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease,” Comparative and Functional Genomics, vol. 4, no. 3, pp. 346–350, 2003. View at Publisher · View at Google Scholar · View at Scopus
  37. A. V. Polonikov, V. P. Ivanov, D. A. Belugin, I. V. Khoroshaya, M. A. Solodilova, and V. I. Panfilov, “Studying associations of two common S27P and −15? > T polymorphisms of the interleukin-3 gene with development of allergic and non-allergic bronchial asthma in Russians from the Central-Chernozem region,” Medical Immunology (Saint Petersburg), vol. 8, no. 5-6, pp. 731–736, 2006. View at Google Scholar
  38. L. Hasselmark, R. Malmgren, G. Unge, and O. Zetterstrom, “Lowered platelet glutathione peroxidase activity in patients with intrinsic asthma,” Allergy, vol. 45, no. 7, pp. 523–527, 1990. View at Google Scholar · View at Scopus
  39. Z. Novák, I. Németh, K. Gyurkovits, S. I. Varga, and B. Matkovics, “Examination of the role of oxygen free radicals in bronchial asthma in childhood,” Clinica Chimica Acta, vol. 201, no. 3, pp. 247–251, 1991. View at Publisher · View at Google Scholar · View at Scopus
  40. C. V. Powell, A. A. Nash, H. J. Powers, and R. A. Primhak, “Antioxidant status in asthma,” Pediatric pulmonology, vol. 18, no. 1, pp. 34–38, 1994. View at Google Scholar · View at Scopus
  41. A. Nadeem, S. K. Chhabra, A. Masood, and H. G. Raj, “Increased oxidative stress and altered levels of antioxidants in asthma,” Journal of Allergy and Clinical Immunology, vol. 111, no. 1, pp. 72–78, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. B. Varshavskiĭ, G. V. Trubnikov, L. P. Galaktionova, N. A. Korenyak, I. L. Kolodeznaya, and A. N. Oberemok, “The oxidative-antioxidative status in patients with bronchial asthma in inhaled and oral glucocorticoid therapy,” Terapevticheskii Arkhiv, vol. 75, no. 3, pp. 21–24, 2003. View at Google Scholar · View at Scopus
  43. L. Bentur, Y. Mansour, R. Brik, Y. Eizenberg, and R. M. Nagler, “Salivary oxidative stress in children during acute asthmatic attack and during remission,” Respiratory Medicine, vol. 100, no. 7, pp. 1195–1201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Chanez, G. Dent, T. Yukawa, P. J. Barnes, and K. F. Chung, “Generation of oxygen free radicals from blood eosinophils from asthma patients after stimulation with PAF or phorbol ester,” European Respiratory Journal, vol. 3, no. 9, pp. 1002–1007, 1990. View at Google Scholar · View at Scopus
  45. I. Vachier, M. Damon, C. le Doucen et al., “Increased oxygen species generation in blood monocytes of asthmatic patients,” American Review of Respiratory Disease, vol. 146, no. 5, pp. 1161–1166, 1992. View at Google Scholar · View at Scopus
  46. I. Rahman, D. Morrison, K. Donaldson, and W. Macnee, “Systemic oxidative stress in asthma, COPD, and smokers,” American Journal of Respiratory and Critical Care Medicine, vol. 154, no. 4, pp. 1055–1060, 1996. View at Google Scholar · View at Scopus
  47. K. R. Shanmugasundaram, S. S. Kumar, and S. Rajajee, “Excessive free radical generation in the blood of children suffering from asthma,” Clinica Chimica Acta, vol. 305, no. 1-2, pp. 107–114, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Beier, K. M. Beeh, D. Semmler, N. Beike, and R. Buhl, “Increased concentrations of glutathione in induced sputum of patients with mild or moderate allergic asthma,” Annals of Allergy, Asthma and Immunology, vol. 92, no. 4, pp. 459–463, 2004. View at Google Scholar · View at Scopus
  49. T. Fujisawa, “Role of oxygen radicals on bronchial asthma,” Current Drug Targets: Inflammation and Allergy, vol. 4, no. 4, pp. 505–509, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. N. L. Reynaert, “Glutathione biochemistry in asthma,” Biochimica et Biophysica Acta, vol. 1810, no. 11, pp. 1045–1051, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. F. J. Kelly and T. Sandström, “Air pollution, oxidative stress, and allergic response,” The Lancet, vol. 363, no. 9403, pp. 95–96, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. S. A. A. Comhair, P. R. Bhathena, R. A. Dweik, M. Kavuru, and S. C. Erzurum, “Rapid loss of superoxide dismutase activity during antigen-induced asthmatic response,” The Lancet, vol. 355, no. 9204, article 624, 2000. View at Google Scholar · View at Scopus
  53. M. T. Salam, P.-C. Lin, E. L. Avol, W. J. Gauderman, and F. D. Gilliland, “Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma,” Thorax, vol. 62, no. 12, pp. 1050–1057, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. K.-Y. Tung, C.-H. Tsai, and Y. L. Lee, “Microsomal epoxide hydroxylase genotypes/diplotypes, traffic air pollution, and childhood asthma,” Chest, vol. 139, no. 4, pp. 839–848, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Hoh and J. Ott, “Mathematical multi-locus approaches to localizing complex human trait genes,” Nature Reviews Genetics, vol. 4, no. 9, pp. 701–709, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. D. M. Nielsen, M. G. Ehm, and B. S. Weir, “Detecting marker-disease association by testing for Hardy-Weinberg disequilibrium at a marker locus,” American Journal of Human Genetics, vol. 63, no. 5, pp. 1531–1540, 1998. View at Publisher · View at Google Scholar · View at Scopus
  57. J. L. Davies, Y. Kawaguchl, S. T. Bennett et al., “A genome-wide search for human type 1 diabetes susceptibility genes,” Nature, vol. 371, no. 6493, pp. 130–136, 1994. View at Publisher · View at Google Scholar · View at Scopus
  58. J. McClellan and M.-C. King, “Genetic heterogeneity in human disease,” Cell, vol. 141, no. 2, pp. 210–217, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. F. D. Martinez, “Complexities of the genetics of asthma,” American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 4, part 2, pp. S117–S122, 1997. View at Google Scholar · View at Scopus
  60. L. I. Holla, K. Kaňková, and V. Znojil, “Haplotype analysis of the NADPH oxidase p22 gene in patients with bronchial asthma,” International Archives of Allergy and Immunology, vol. 148, no. 1, pp. 73–80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Morin, J. R. Brook, C. Duchaine, and C. Laprise, “Association study of genes associated to asthma in a specific environment, in an asthma familial collection located in a rural area influenced by different industries,” International Journal of Environmental Research and Public Health, vol. 9, no. 8, pp. 2620–2635, 2012. View at Publisher · View at Google Scholar
  62. D. Daley, M. Lemire, L. Akhabir et al., “Analyses of associations with asthma in four asthma population samples from Canada and Australia,” Human Genetics, vol. 125, no. 4, pp. 445–459, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Minelli, R. Granell, R. Newson et al., “Glutathione-S-transferase genes and asthma phenotypes: a Human Genome Epidemiology (HuGE) systematic review and meta-analysis including unpublished data,” International Journal of Epidemiology, vol. 39, no. 2, Article ID dyp337, pp. 539–562, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. J. H. Moore, J. C. Gilbert, C.-T. Tsai et al., “A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility,” Journal of Theoretical Biology, vol. 241, no. 2, pp. 252–261, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. I. Rahman, S. K. Biswas, and A. Kode, “Oxidant and antioxidant balance in the airways and airway diseases,” European Journal of Pharmacology, vol. 533, no. 1–3, pp. 222–239, 2006. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Nadeem, A. Masood, and N. Siddiqui, “Oxidant—antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options,” Therapeutic Advances in Respiratory Disease, vol. 2, no. 4, pp. 215–235, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. B. Gaston, “The biochemistry of asthma,” Biochimica et Biophysica Acta, vol. 1810, no. 11, pp. 1017–1024, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. E. Babusikova, J. Jurecekova, A. Evinova, M. Jesenak, and D. Dobrota, “Oxidative damage and bronchial asthma in respiratory diseases,” in Respiratory Diseases, M. Ghanei, Ed., InTech, Rijeka, Croatia, 2012. View at Publisher · View at Google Scholar
  69. N. Li, M. Hao, R. F. Phalen, W. C. Hinds, and A. E. Nel, “Particulate air pollutants and asthma: a paradigm for the role of oxidative stress in PM-induced adverse health effects,” Clinical Immunology, vol. 109, no. 3, pp. 250–265, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Ober, D. A. Loisel, and Y. Gilad, “Sex-specific genetic architecture of human disease,” Nature Reviews Genetics, vol. 9, no. 12, pp. 911–922, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. K. Mittelstrass, J. S. Ried, Z. Yu et al., “Discovery of sexual dimorphisms in metabolic and genetic biomarkers,” PLoS Genetics, vol. 7, no. 8, Article ID e1002215, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. D. S. Postma, “Gender differences in asthma development and progression,” Gender Medicine, vol. 4, supplement 2, pp. S133–S146, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. L. A. Weiss, L. Pan, M. Abney, and C. Ober, “The sex-specific genetic architecture of quantitative traits in humans,” Nature Genetics, vol. 38, no. 2, pp. 218–222, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. K. M. Egan, J. A. Lawson, S. Fries et al., “COX-2-derived prostacyclin confers atheroprotection on female mice,” Science, vol. 306, no. 5703, pp. 1954–1957, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. R. Angelopoulou, G. Lavranos, and P. Manolakou, “Establishing sexual dimorphism in humans,” Collegium Antropologicum, vol. 30, no. 3, pp. 653–658, 2006. View at Google Scholar · View at Scopus
  76. C. Borrás, J. Sastre, D. García-Sala, A. Lloret, F. V. Pallardó, and J. Viña, “Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males,” Free Radical Biology and Medicine, vol. 34, no. 5, pp. 546–552, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Vina, C. Borras, M.-C. Gomez-Cabrera, and W. C. Orr, “Part of the series: from dietary antioxidants to regulators in cellular signalling and gene expression. Role of reactive oxygen species and (phyto)oestrogens in the modulation of adaptive response to stress,” Free Radical Research, vol. 40, no. 2, pp. 111–119, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. T. L. Bonfield and K. R. Ross, “Asthma heterogeneity and therapeutic options from the clinic to the bench,” Current Opinion in Allergy and Clinical Immunology, vol. 12, no. 1, pp. 60–67, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. R. A. Mathias, “Introduction to genetics and genomics in asthma: genetics of asthma,” in Heterogeneity in Asthma, pp. 125–155, Springer, New York, NY, USA, 2014. View at Google Scholar