Genetic deficiency of human mast cell a‐tryptase

摘要: BACKGROUND Human alpha- and beta-tryptases are proteases secreted by mast cells. Beta (but not alpha) tryptases implicated in asthma. Genes encoding both types of cluster on chromosome 16p13.3. OBJECTIVE This study examines the hypothesis, generated from mapping data, that alpha-alleles compete with some beta-alleles at one locus an adjacent contains exclusively. hypothesis predicts outnumber alpha genomes lack genes altogether. METHODS To test this we developed PCR-based techniques to distinguish beta genes. We then genotyped genomic DNA individuals tryptase-expressing cell lines. RESULTS In support our find alpha-tryptase deficiency affects 80/274 (29%) surveyed. The genotype alpha-deficient is betabetabetabeta, due inheritance four percentage population mixed genotypes alphaalphabetabeta alphabetabetabeta 21% 50%, respectively. Accounting for all tandem loci 16p13.3, overall alpha-allele frequency only 0.23, considerably outnumbering as hypothesized. samples defined ethnicity, 45% Caucasians, but a much lower other backgrounds, including African-Americans Asians. Examination lines reveals HMC-1 U-937 alpha-genes; thus, transcripts these cells absence alpha-genes rather than beta-selective transcription. By contrast, alpha-transcribing Mono Mac 6 KU812 contain beta-genes. CONCLUSIONS Genetic common varies strikingly between ethnic groups. Because allergic disorders, inherited differences alpha/beta-genotype may affect disease susceptibility, severity response tryptase inhibitor therapy.