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Article Details


Genomics and Pharmacogenomics of Rhinosinusitis

[ Vol. 17 , Issue. 2 ]

Author(s):

Joaquin Guerra*, Juan Carlos Carril, Margarita Alcaraz, Marcos Santiago, Lola Corzo and Ramon Cacabelos   Pages 114 - 124 ( 11 )

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.

Affiliation:

Neuro-Otolaryngology Unit., 151615 Bergondo, Corunna, Department of Genomics, 151615 Bergondo, Corunna, Department of Clinical Neuroscience and Genomic Medicine, 151615 Bergondo, Corunna, Department of Neuroimaging, 151615 Bergondo, Corunna, Department of Clinical Biochemistry, 151615 Bergondo, Corunna, Department of Clinical Neuroscience and Genomic Medicine, 151615 Bergondo, Corunna

Graphical Abstract:



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