Genetics of asthma: a molecular biologist perspective

The realization that asthma is a genetic disorder, which runs in families, is relatively old and can roughly be dated back to the early 20th century, where investigators sought to identify traits with simple Mendelian mode of inheritance responsible for asthma pathogenesis [1]. Later, epidemiological surveys were conducted that demonstrated the heritability of asthma using twin studies [2]. Owing to the variable phenotypes that asthma presents with [3], defining it clinically has been challenging and no definitions so far have been fool proof, in terms of sensitivity and specificity [4]. The definitions and guidelines have seen transformations from time to time depending upon our understanding of its etiopathology [5]. Put in its simplest form, asthma is a chronic pulmonary disorder which is characterized by airway inflammation and remodeling that leads to reversible airway obstruction [3]. Inflammation is seen mainly in the larger conducting airways; however in severe forms of asthma even the smaller airways show infiltration of immune cells [6]. Asthma represents a spectrum of disease and apart from symptoms like wheezing and breathing difficulty; cough, running nose and eyes, dyspnoea etc. may accompany it with variable degree and frequency. Inherent genetic factors interact in complex fashion, with environmental triggers, to bring about its pathogenesis and depending upon the trigger, it is classified as extrinsic or intrinsic asthma [7]. Extrinsic asthma results from hypersensitivity reactions (such as wheal and flare reaction to intradermal allergens), resulting in increased serum IgE and bronchial hyper-responsiveness to specific or non-specific inhaled allergens [7]. In contrast intrinsic asthma is thought to be non-immune and without any atopic background. We mainly focus on extrinsic asthma, where there is plenty of genetic data to build up a sketch of the molecular biology pathways that play significant role in its pathogenesis. Also, the molecular mechan