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.