Recent developments in asthma-related genes
Genetic factors have a strong impact on the risk of developing asthma.2 In particular, childhood asthma is strongly associated with the 17q21 locus alleles. Analyzing 14 different populations of asthmatic patients from 12 different countries, Farzan et al. showed that 17q21 polymorphism is related to an increased risk of exacerbations in children with asthma despite ICS use.14 The authors also observed that the SNP rs7216389 frequency was higher in East Asians, African Americans and Hispanics, compared to patients of European ancestry.14 Interestingly, an interaction between 17q21 variants and breastfeeding in relation to respiratory symptoms in the first year of life was observed by Gorlanova et al., suggesting a protective effect of breastfeeding on asthma inception linked to early‐life respiratory infections in babies carrying the risk alleles. Specifically, when infants were stratified by breastfeeding status, carriers of asthma risk alleles showed a protective effect of breastfeeding on respiratory symptoms during the weeks when they were breastfed, while they showed an increased risk of respiratory symptoms during the weeks when they were not breastfed.15 TheORMDL3 gene, also related to the 17q21 region, plays an important role as well. There are higher levels of human lung ORMDL3 and its SNPs rs8076131 from asthmatic patients than the healthy subjects.16
Associations between childhood asthma phenotypes and genetic, immunological, and environmental factors have been largely established whereas there is a lack of strategies to integrate high‐dimensional risk factors from multiple distinct data sets and thereby increase the statistical power of analyses.17 In many studies the classification of childhood asthma phenotypes is often based on assessment of singular risk factors measurements only. Krautenbacher et al. evaluated a new strategy combining cytokine, genotype, flow cytometry, diagnostic, questionnaire, Reverse transcription polymerase chain reaction (RT‐PCR), and microarray data by using an integrative multilevel learning approach. Following this new discovery approach genes such as PKN2 (protein kinase N2), PTK2 (protein tyrosine kinase 2), and ALPP (alkaline phosphatase, placental) seem to be the most important asthma risk factors.18
Interleukin 1 receptor-like 1 (ST2) is known to be related to the pathogenesis of allergic diseases by mediating the response to IL-33.Interleukin 1 receptor-like 1 (ST2) single‐nucleotide polymorphisms (SNPs) rs13431828, rs1420101, rs1921622, and rs10204137 were related to reduced efficacy of ICS in children and adolescents.19
Recently, Olafsdottir et al.3 demonstrated 88 asthma risk genome variants at 56 loci, 19 previously unreported, in a genome-wide association meta-analysis. They investigated the effect of asthma-associated variants and their genetic correlation between asthma and allergic phenotypes as well. They suggest a missense variant inTNFRSF8 and a 3’ untranslated region variant in TGFBR1 to be related to decreased asthma risk. In a study on the Hispanic/Latino population in the US genetic predisposition to obesity was found as a risk factor for asthma, especially for childhood-onset asthma in females4.