Association studies of 33 single nucleotide polymorphisms (SNPs) in 29 candidate genes for bronchial asthma: positive association of a T924C polymorphism in the thromboxane A2 receptor gene

Abstract

Although intensive studies have attempted to elucidate the genetic background of bronchial asthma (BA), one of the most common of the chronic inflammatory diseases in human populations, genetic factors associated with its pathogenesis are still not well understood. We surveyed 29 possible candidate genes for this disease for single nucleotide polymorphisms (SNPs), the most frequent type of genetic variation, in genomic DNAs from Japanese BA patients. We identified 33 SNPs, only four of which had been reported previously, among 14 of those genes. We also performed association studies using 585 BA patients and 343 normal controls for these SNPs. Of the 33 SNPs tested, 32 revealed no positive association with BA, but a T924C polymorphism in the thromboxane A2 receptor gene showed significant association (chi2=4.71, P=0.030), especially with respect to adult patients (chi2=6.20, P=0.013). Our results suggest that variants of the TBXA2R gene or some nearby gene(s) may play an important role in the pathogenesis of adult BA.

Thromboxane A2 receptor +795T>C and chemoattractant receptor-homologous molecule expressed on Th2 cells -466T>C gene polymorphisms in patients with aspirin-exacerbated respiratory disease

“…Conflicting results about the genetic alteration of TBXA2R in the involvement of asthma have been reported in an Asian population (13)(14)(15). Genetic alteration of CRTH2 has been correlated to allergic asthma in African-American and Chinese populations (18), but not in a Japanese population (19).…”

“…On the other hand, Kim et al (14) showed that the TBXA2R polymorphism was not associated with asthma susceptibility and the clinical parameters of asthma. In a Japanese population, Unoki et al (15) found that the synonymous +924T>C polymorphism in the TBXA2R gene was associated with a diagnosis of asthma in adult asthmatic patients, but not in children. However, their claim of an involvement of TBXA2R in Japanese asthmatics does not seem to be substantiated by their data (16,17).…”

Association between the TRAIL single nucleotide polymorphism rs1131580 and type 2 diabetes mellitus in a Han Chinese population

“…There are several SNPs in TRAIL, including 4 SNPs in the 5ꞌ-regulatory region, 2 SNPs within exons, and 5 SNPs in the 3ꞌ-untranslated region (3ꞌ-UTR) (Unoki et al, 2000;Wang et al, 2000;Gray et al, 2001). Generally, 3'-UTR has wide-range influences on gene regulation (Zhang et al, 2004;Watanabe et al, 2007).…”

Identification and allelic frequencies of novel single-nucleotide polymorphisms in the DUSP1 and BTG1 genes

“…SNPs were genotyped by allele-specific oligonucleotide (ASO) hybridization as described previously (Unoki et al 2000). Allele-specific probes ( 32 P-labeled 13-to 17-mers) of 5Ј-TACGCCCTCGGGG-3Ј or 5Ј-TACGCC GTCGGGG-3Ј for C(IVS ϩ 8)G of DUSP1, and 5Ј-GGGTGGCTGCTCC-3Ј or 5Ј-GGGTGGTTGCTCC-3Ј for C(-67T) of BTG1, were hybridized at 37°C to the polymerase chain reaction (PCR) products on the membranes and washed in 6 ϫ standard saline citrate (SSC) at 42°C (DUSP1) or at 46°C (BTG1) according to standard protocols.…”