Variable expression of cysteinyl leukotriene type I receptor splice variants in asthmatic females with different promoter haplotypes

• Main Authors: Bednarek Andrzej K, Seta Karolina, Cieslak Malgorzata, Wodz-Naskiewicz Karolina, Sokolowska Milena, Pawliczak Rafal
• Format: Article
• Language: English
• Published: BMC 2009-12-01
• Series: BMC Immunology
• Online Access: http://www.biomedcentral.com/1471-2172/10/63

<p>Abstract</p> <p>Background</p> <p>Cysteinyl leukotrienes are potent inflammatory mediators implicated in the pathogenesis of asthma. Human cysteinyl leukotriene receptor 1 (<it>CYSLTR1</it>) gene contains five exons that are variably spliced. Within its promoter few polymorphisms were described. To date, there has been no evidence about the expression of different splice variants of CysLT₁in asthma and their association with <it>CYSLTR1 </it>promoter polymorphisms.</p> <p>The goal of our study was to investigate CysLT₁alternative transcripts expression in asthmatic patients with different <it>CYSLTR1 </it>promoter haplotypes.</p> <p>The study groups consisted of 44 patients with asthma, diagnosed according to GINA 2008 criteria and 18 healthy subjects. Genomic DNA and total RNA was extracted from peripheral blood mononuclear cells. Real-time PCR was performed with specific primers for transcript I [GenBank:<ext-link ext-link-id="DQ131799" ext-link-type="gen">DQ131799</ext-link>] and II [GenBank:<ext-link ext-link-id="DQ131800" ext-link-type="gen">DQ131800</ext-link>]. Fragments of the <it>CYSLTR1 </it>promoter were amplified by PCR and sequenced directly to identify four single nucleotide polymorphisms: C/T [SNP:rs321029], A/C [SNP:rs2637204], A/G [SNP:rs2806489] and C/T [SNP:rs7066737].</p> <p>Results</p> <p>The expression of CysLT₁transcript I and II in asthma did not differ from its expression in healthy control group. However, in major alleles homozygotic CAAC/CAAC women with asthma we found significantly higher expression of transcript I as compared to heterozygous CAAC/TCGC women in that loci. CysLT₁transcript I expression tended to negative correlation with episodes of acute respiratory infection in our asthmatic population. Moreover, expression of CysLT₁transcript II in CAAC/CAAC homozygotic women with asthma was significantly lower than in CAAC/CAAC healthy control females.</p> <p>Conclusions</p> <p>Genetic variants of <it>CYSLTR1 </it>promoter might be associated with gender specific expression of CysLT₁alternative transcripts in patients with asthma. CysLT₁splice variants expression might also correlate with the susceptibility to infection in asthmatic population.</p>