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Current Pharmacogenomics and Personalized Medicine

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ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

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Research Article

Genomics and Pharmacogenomics of Rhinosinusitis

Author(s): Joaquin Guerra*, Juan Carlos Carril, Margarita Alcaraz, Marcos Santiago, Lola Corzo and Ramon Cacabelos

Volume 17, Issue 2, 2020

Page: [114 - 124] Pages: 11

DOI: 10.2174/1875692117999200801024849

Price: $65

Abstract

Background: Polymorphisms of selected inflammatory and metabolic genes have been described in the etiology of chronic rhinosinusitis, and these effects can be explained on a pharmacogenetic basis.

Objective: The purpose of this study was to examine whether there is an association between inflammatory factors and some of these alleles, by associating these genetic variables with each other.

Methods: CYP1A2, CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, G6PD, NAT2, UGT1A1, VKORC1, ABCB1, SLCO1B1, APOE, TNF, IL1B, IL6 and IL6R gene polymorphisms were analyzed by PCR. Drug-metabolizing enzymes were classified according to their phenotype. Blood cell counts and biochemical parameters were also considered.

Results: Significant differences were found in the CYP1A2 phenotype, with fewer CYP1A2 normal metabolizers (NMs) expressing sinusitis (14.3% vs 30%) and a greater number of CYP1A2 ultra-rapid-metabolizers (UMs)(85% vs 69%); and in TNF, affecting TNF-A/A (4% vs 2%) and TNF-G/G (78% vs 66%) compared with TNF-G/A (19% vs 32%) carriers. 96% of patients with CRS had at least one G allele. When trigenic variables involved in sinusitis were analyzed, statistical differences were found in SLCO1B1-TNFCYP1A2, with a higher proportion of subjects with 1/1-GG-UM (44.3%); and IL1B-TNFCYP1A2 with CC-GG-UM (26%), CT-GG-UM (19.8%) and CC-GG-NM (13.7%) genophenotypes, respectively. Subjects with sinusitis had a higher eosinophil count (308.80 cel/mcL vs 263.14 cel/mcL) and lower HDL levels (265.34 vs 297.85 mg/dL).

Conclusion: SLCO1B1-TNF-CYP1A2 and IL1B-TNF-CYP1A2 trigenic clusters may condition the chronicity of sinusitis. Eosinophilia and HDL are factors involved in inflammation, and thus in the development of CRS.

Keywords: Sinusitis, genomics, geno-phenotype, CYPs, TNF, Eosinophils, HDL, IL1B, SLCO1B1.

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[1]
Bachert C, Van Bruaene N, Toskala E, Zhang N, Olze H, Scadding G, et al. Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GALEN study. Allergy 2009; 64(4): 520-33.
[http://dx.doi.org/10.1111/j.1398-9995.2009.01964.x ] [PMID: 19317839]
[2]
Payne SC, Borish L, Steinke JW. Genetics and phenotyping in chronic sinusitis. J Allergy Clin Immunol 2011; 128(4): 710-20.
[http://dx.doi.org/10.1016/j.jaci.2011.05.022] [PMID: 21704364]
[3]
Rudmik L, Soler ZM. Medical therapies for adult chronic sinusitis: A systematic review. JAMA 2015; 314(9): 926-39.
[http://dx.doi.org/10.1001/jama.2015.7544 ] [PMID: 26325561]
[4]
DeConde AS, Smith TL. classification of chronic rhinosinusitis-working toward personalized diagnosis. Otolaryngol Clin North Am 2017; 50(1): 1-12..
[http://dx.doi.org/10.1016/j.otc.2016.08.003] [PMID: 27888907]
[5]
Lopatin AS, Ivanchenko OA, Soshnikov SS, Mullol J. Cyclamen europaeum improves the effect of oral antibiotics on exacerbations and recurrences of chronic rhinosinusitis: A real-life observational study (CHRONOS). Acta Otorhinolaryngol Ital 2018; 38(2): 115-23.
[PMID: 29967550]
[6]
Cho SH, Kim DW, Lee SH, Kolliputi N, Hong SJ, Suh L, et al. Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling. Am J Respir Cell Mol Biol 2015; 53(5): 601-6.
[http://dx.doi.org/10.1165/rcmb.2015-0207RC] [PMID: 26266960]
[7]
Goodman DM, Lynm C, Livingston EL. JAMA patient page. Adult sinusitis. JAMA 2013; 309(8): 837.
[http://dx.doi.org/10.1001/jama.2013.1137 ] [PMID: 23443449]
[8]
Lee S, Lane AP. Chronic rhinosinusitis as a multifactorial inflammatory disorder. Curr Infect Dis Rep 2011; 13(2): 159-68.
[http://dx.doi.org/10.1007/s11908-011-0166-z ] [PMID: 21365379]
[9]
Huvenne W, van Bruaene N, Zhang N, van Zele T, Patou J, Gevaert P, et al. Chronic rhinosinusitis with and without nasal polyps: What is the difference? Curr Allergy Asthma Rep 2009; 9(3): 213-20.
[http://dx.doi.org/10.1007/s11882-009-0031-4] [PMID: 19348721]
[10]
Hsu J, Avila PC, Kern RC, Hayes MG, Schleimer RP, Pinto JM. Genetics of chronic rhinosinusitis: State of the field and directions forward. J Allergy Clin Immunol 2013; 131(4):977-993, 993.e1-993.e5..
[http://dx.doi.org/10.1016/j.jaci.2013.01.028] [PMID: 23540616]
[11]
Bernstein JM, Anon JB, Rontal M, Conroy J, Wang C, Sucheston L. Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis. Laryngoscope 2009; 119(7): 1258-64.
[http://dx.doi.org/10.1002/lary.20239 ] [PMID: 19405090]
[12]
Khawar MB, Abbasi MH, Sheikh N. IL-32: A novel pluripotent inflammatory interleukin, towards gastric inflammation, gastric cancer, and chronic rhino sinusitis. Mediators Inflamm 2016. 20168413768
[http://dx.doi.org/10.1155/2016/8413768 ] [PMID: 27143819]
[13]
Stavropoulou E, Pircalabioru GG, Bezirtzoglou E. The role of cytochromes P450 in infection. Front Immunol 2018; 9: 89.
[http://dx.doi.org/10.3389/fimmu.2018.00089] [PMID: 29445375]
[14]
Cacabelos R, Meyyazhagan A, Carril JC, Cacabelos P, Teijido O. Pharmacogenetics of vascular risk factors in alzheimer’s disease. J Pers Med 2018; 8(1) E3
[http://dx.doi.org/10.3390/jpm8010003] [PMID: 29301387]
[15]
Szabo K, Kiricsi A, Revesz M, Vona I, Bella Z, Polyanka H, et al. The -308 G>A SNP of TNFA is a factor predisposing to chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarian individuals: Conclusions of a genetic study with multiple stratifications. Int Immunol 2013; 25(6): 383-8.
[http://dx.doi.org/10.1093/intimm/dxs162 ] [PMID: 23446846]
[16]
Ismi O, Ozcan C, Polat G, et al. TNF- α and IL-1 β cytokine gene polymorphism in patients with nasal polyposis. Turk Arch Otorhinolaryngol 2017; 55(2): 51-6.
[http://dx.doi.org/10.5152/tao.2017.2389 ] [PMID: 29392055]
[17]
Takeuchi K, Majima Y, Sakakura Y. Tumor necrosis factor gene polymorphism in chronic sinusitis. Laryngoscope 2000; 110(10 Pt 1): 1711-4.
[http://dx.doi.org/10.1097/00005537-200010000-00027 ] [PMID: 11037831]
[18]
Mfuna Endam L, Cormier C, Bosse Y, Filali-Mouhim A, Desrosiers M. Association of IL1A, IL1B, and TNF gene polymorphisms with chronic rhinosinusitis with and without nasal polyposis: A replication study. Arch Otolaryngol Head Neck Surg 2010; 136(2): 187-92.
[http://dx.doi.org/10.1001/archoto.2009.219 ] [PMID: 20157068]
[19]
Vrzal R, Ulrichova J, Dvorak Z. Aromatic hydrocarbon receptor status in the metabolism of xenobiotics under normal and pathophysiological conditions. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2004; 148(1): 3-10.
[http://dx.doi.org/10.5507/bp.2004.001 ] [PMID: 15523539]
[20]
Abdel-Razzak Z, Loyer P, Fautrel A, Gautier JC, Corcos L, Turlin B, et al. Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol Pharmacol 1993; 44(4): 707-15.
[PMID: 8232220]
[21]
Cacabelos R. World guide for drug use and pharmacogenomics. Spain: EuroEspes Publishing 2012.
[22]
Le Saux N. The treatment of acute bacterial sinusitis: No change is good medicine. CMAJ 2008; 178(7): 865-6.
[http://dx.doi.org/10.1503/cmaj.080285 ] [PMID: 18362382]
[23]
Cheng YK, Lin CD, Chang WC, Hwang GY, Tsai SW, Wan L, et al. Increased prevalence of interleukin-1 receptor antagonist gene polymorphism in patients with chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg 2006; 132(3): 285-90.
[http://dx.doi.org/10.1001/archotol.132.3.285] [PMID: 16549749]
[24]
Mohamad S, Hamid SSA, Azlina A, Md Shukri N. Association of IL-1 gene polymorphisms with chronic rhinosinusitis with and without nasal polyp. Asia Pac Allergy 2019; 9(3) e22
[http://dx.doi.org/10.5415/apallergy.2019.9.e22]] [PMID: 31384577]
[25]
Baroody FM, Suh SH, Naclerio RM. Total IgE serum levels correlate with sinus mucosal thickness on computerized tomography scans. J Allergy Clin Immunol 1997; 100(4): 563-8.
[http://dx.doi.org/10.1016/S0091-6749(97)70151-9 ] [PMID: 9338553]
[26]
Sreeparvathi A, Kalyanikuttyamma LK, Kumar M, Sreekumar N, Veerasigamani N. Significance of blood eosinophil count in patients with chronic rhinosinusitis with nasal polyposis. J Clin Diagn Res 2017; 11(2): MC08-11.
[http://dx.doi.org/10.7860/JCDR/2017/25320.9445 ] [PMID: 28384896]
[27]
Navab M, Anantharamaiah GM, Fogelman AM. The role of high-density lipoprotein in inflammation. Trends Cardiovasc Med 2005; 15(4): 158-61.
[http://dx.doi.org/10.1016/j.tcm.2005.05.008] [PMID: 16099381]
[28]
Feingold KR, Grunfeld C. The effect of inflammation and infection on lipids and Lipoproteins. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, et al, Eds. Endotext. South Dartmouth (MA): MDText.com, Inc 2000.
[29]
Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N. lee SE, et al Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): Results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 2019; 394(10209): 1638-50.
[http://dx.doi.org/10.1016/S0140-6736(19)31881-1 ] [PMID: 31543428]

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