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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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