Human adenosine 2B receptor: SNP discovery and evaluation of expression in patients with cystic fibrosis

Abstract

We analyzed the adenosine 2B (A2B) receptor gene, which consists of two exons, for single nucleotide polymorphisms (SNPs) and tested the hypothesis that coding sequence polymorphisms in the gene contribute to disease state in patients with cystic fibrosis (CF). Using PCR and restriction fragment length polymorphism (RFLP) analysis, we assessed 53 American subjects of mixed ethnicity, 64 European Caucasian control subjects and 148 Caucasian patients with CF for A2B SNPs. We identified one SNP in the 5' untranslated region (UTR) and seven SNPs in the open reading frame. One SNP was identified in the coding region of a German patient with CF but in none of the American subjects. No other SNPs were found in CF patients. A nonsynonymous SNP was identified in exon 2 of the German controls with an allelic frequency of 11%. The US subjects were of mixed ethnicity and most frequently (10.4%) had a SNP in the 5'UTR; 7 coding SNPs occurred in <3%. All SNPs other than the Leu96Phe and Gly136Arg variants were found only in African-Americans. Of the 26 African-Americans who were genotyped, 42% were hypertensive but the study group was too small to show an association between blood pressure status and SNP expression. The data show that SNPs in the A2B receptor gene are much more frequent in African-Americans than in Caucasians and that German Caucasians, but not African-Americans, express Gly136Arg. None of the SNPs identified in A2B receptors are likely to be modifiers in CF.