Title:Genomics and Pharmacogenomics of Rhinosinusitis
Volume: 17
Issue: 2
Author(s): Joaquin Guerra*, Juan Carlos Carril, Margarita Alcaraz, Marcos Santiago, Lola Corzo and Ramon Cacabelos
Affiliation:
- Neuro-Otolaryngology Unit., 151615 Bergondo, Corunna,Spain
Keywords:
Sinusitis, genomics, geno-phenotype, CYPs, TNF, Eosinophils, HDL, IL1B, SLCO1B1.
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.
