Genomics and Pharmacogenomics of Rhinosinusitis

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.