Chinmoyee Das

β2-adrenergic receptor polymorphisms and response to salbutamol among Indian asthmatics∗

INTRODUCTION The beta(2)-adrenergic receptor (beta(2)AR or ADRbeta(2)) is the target for beta(2)-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The aim of this study was to identify common single nucleotide polymorphisms (SNPs) and haplotypes in asthmatics and healthy individuals from an Indian population, and determine the influence of beta(2)AR SNPs in responsiveness to beta(2)-agonist therapy in asthma patients. METHODS Ten variable SNP sites within a span of 2.193 kb were identified in the beta(2)AR gene by sequencing and genotyping 374 bronchial asthma patients and healthy individuals from an Indian population. Spirometry tests were performed on 80 unrelated patients before and after administration of 200 microg of salbutamol. A post-bronchodilator forced expiratory volume in one second (FEV(1)) change of >or= 15.3% was considered a good response, and a change of<15.3% was defined as a poor response, to salbutamol. RESULTS The pattern of linkage disequilibrium between the ten SNPs showed a single, linked SNP block consisting of sites -468, -367, -47, -20, and 79 having strong linkage disequilibrium, while the SNPs at sites -1023, -654, 46, 252, and 523 showed very low linkage with one another and with the linked region. The SNPs were found to be organized into 16 haplotypes in the studied population. We found that patients with a homozygous Arg-16 form at nucleotide position 46 are poor responders with probability of 0.81, and patients with a homozygous Gly-16 form are good responders with a probability of 0.73. The responder status to salbutamol treatment and the genotype at nucleotide position 46 in beta(2)AR gene of an asthmatic patient are significantly associated in the studied Indian population (chi2=9.98, df=2, p=0.0068). Most importantly, this association for responsiveness to salbutamol at nucleotide position 46 is independent of other SNPs in the beta(2)AR gene. CONCLUSION This study suggests that the SNP at nucleotide position 46 has particular relevance to pharmacogenetics in the Indian population studied.

Invasive tracheobronchial aspergillosis in an immunocompetent person.

Tracheobronchial involvement is an uncommon form of invasive pulmonary aspergillosis and is found mainly in immunocompromised individuals such as patients with leukemia and prolonged granulocytopenia due to cytotoxic therapy, organ transplant recipients receiving high-dose corticosteroids, or patients with chronic granulomatous diseases. Rarely, such a pattern can also be seen in immunocompetent persons or can involve atypical sites such as the paranasal sinuses, skin, and the tracheobronchial tree. Occasionally, these patients require a prolonged course of antifungal agents. We report a case of aspergillosis involving the tracheobronchial tree in an immunocompetent young male that presented a diagnostic dilemma.