Determination of structure and transcriptional regulation of CYSLTR1 and an association study with asthma and rhinitis.
Pharmacologic studies have revealed that cysteinyl leukotrienes (CYSLTs) act through two receptors, cysteinyl leukotriene receptor 1 (CYSLTR1) and CYSLTR2. CYSLTR1 antagonists are widely used to treat asthma and rhinitis. In this study, we characterized the genomic structure and transcriptional regulation of CYSLTR1 and examined associations between CYSLTR1 polymorphisms and asthma/rhinitis. The experiment of rapid amplification of cDNA end revealed that CYSLTR1 contains three exons and that the entire open reading frame is located in exon 3. Reverse transcriptase-polymerase chain reaction showed that there were multiple splice variants of CYSLTR1 and that the transcript expression patterns differed from tissues and cell types. The promoter region of CYSLTR1 is from -665 to -30 bp relative to the transcription start site. We identified four polymorphisms (c.-618-434T/C, c.-618-275C/A, c.-618-136G/A, and 927C/T), and transmission disequilibrium tests revealed that none of these polymorphisms was associated with the development of asthma/rhinitis. However, the TCG and CAA haplotypes in the promoter region caused different transcriptional activity. Our findings indicate that CYSLTR1 polymorphisms are not likely to be involved in the development of asthma/rhinitis, but it is possible that these polymorphisms could influence drug responses in individuals with atopic diseases.
Zhang
Jian
J
Department of Medical Genetics, Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba City, Japan.
Migita
Ohsuke
O
Koga
Minori
M
Shibasaki
Masanao
M
Arinami
Tadao
T
Noguchi
Emiko
E
D000293:Adolescent; D017398:Alternative Splicing; D000595:Amino Acid Sequence / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D002648:Child; D005786:Gene Expression Regulation / Q000235:genetics; D040481:Genome Components / Q000235:genetics*; D006801:Humans; D007564:Japan; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000235:genetics; D018077:Receptors, Leukotriene / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor