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

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 (FEV1) 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.