Association analysis of DTD1 gene variations with aspirin-intolerance in asthmatics

Abstract

Abstract. Aspirin ingestion is a common precipitating factor of life-threatening asthma attacks, requiring some patients to undergo mechanical ventilation. The gene, d-tyrosyl-tRNA deacylase 1 (DTD1), may be a risk factor for aspirin-intolerant asthma (AIA) by catalyzing the hydrolysis of d-tryptophan and interacting with the tyrosyl-tRNA synthetase (tyrRS) enzyme, which promotes a pro-inflammatory phenotype. In order to investigate the association of DTD1 variants with the risk of AIA in an asthma cohort, 38 single nucleotide polymorphisms (SNPs) were genotyped and 5 major haplotypes were obtained in 163 AIA cases and 429 aspirin-tolerant asthma (ATA) controls. differences in DTD1 SNP and haplotype distributions were analyzed using logistic and multiple regression models and were adjusted for age, gender, smoking status, atopy and body mass index (BMI) as covariates. Subsequent analyses revealed no association between DTD1 variants and the risk of AIA. Although nominal evidence of an association was detected between several DTD1 variants and the rate of decline of the forced expiratory volume in the first second (FEV 1 ) in AIA patients (rs6136444, rs6136469, rs6081338 and DTD1_ht5; P=0.01-0.02), the signals reached the threshold of multiple testing corrections, suggesting that DTD1 variants do not affect the abnormalities of the upper airways in AIA patients.

Genome-Wide Interaction Study of Omega-3 PUFAs and Other Fatty Acids on Inflammatory Biomarkers of Cardiovascular Health in the Framingham Heart Study

“…There is evidence, however, that this gene is associated with higher levels of DHA as well as with generally higher Omega-3 and Omega-6 FA levels [ 55 ]. DTD1 also may be a risk factor for aspirin-intolerant asthma through a mechanism that promotes a pro-inflammatory phenotype [ 56 ].…”

Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders

“…Based on this pattern we hypothesize that the causal variant in this locus induces a shift in the choice of FAs absorbed from diet, or in the specificity towards FAs incorporated into erythrocyte membrane lipids. The observed association signals mapped to DTD1 , however, the product of this gene has no known functional link to FA-metabolic pathways [ 30 ]. The gene-rich region contains other possible causal candidate genes, among these are SCP2D1 .…”

Possible role of EMID2 on nasal polyps pathogenesis in Korean asthma patients

“…Written informed consent was secured from each patient before blood was drawn, and the study protocols were approved by the Institutional Review Board of each participating hospital. Following the guidelines of Global Initiative for Asthma (GINA), asthma was diagnosed as described previously [7]. Twenty-four common inhalant allergens were used in a skin-prick test (Bencard Co. Ltd., Brentford, UK), and atopy was defined as at least a 3-mm wheal reaction to any of the allergens.…”

“…To distinguish AERD patients from aspirin-tolerant asthma (ATA) subgroups, all asthma patients underwent oral aspirin challenge (OAC) that was performed according to our previous methods [7]. Asthmatics exhibiting ≥ 20% decrease in FEV 1 or a 15-19% decrease in FEV 1 with naso-ocular or cutaneous reactions were categorized in the AERD group, whereas those demonstrating < 15% decrease in FEV 1 without naso-ocular or cutaneous reactions classified into the aspirin-tolerant asthma (ATA) group.…”