Genetic variations in olfactory receptor gene OR2AG2 in a large multigenerational family with asthma

Abstract

It is estimated from twin studies that heritable factors account for at-least half of asthma-risk, of which genetic variants identified through population studies explain only a small fraction. Multi-generation large families with high asthma prevalence can serve as a model to identify highly penetrant genetic variants in closely related individuals that are missed by population studies. To achieve this, a four-generation Indian family with asthma was identified and recruited for examination and genetic testing. Twenty subjects representing all generations were selected for whole genome genotyping, of which eight were subjected to exome sequencing. Non-synonymous and deleterious variants, segregating with the affected individuals, were identified by exome sequencing. A prioritized deleterious missense common variant in the olfactory receptor gene OR2AG2 that segregated with a risk haplotype in asthma, was validated in an asthma cohort of different ethnicity. Phenotypic tests were conducted to verify expected deficits in terms of reduced ability to sense odors. Pathway-level relevance to asthma biology was tested in model systems and unrelated human lung samples. Our study suggests that OR2AG2 and other olfactory receptors may contribute to asthma pathophysiology. Genetic studies on large families of interest can lead to efficient discovery.

A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

“…Interestingly, ex vivo data demonstrated that stress induces a significant down-regulation of the expression of skin OR10A6 and OR2AG2, both at the mRNA and protein levels. Such an effect was already observed for OR2AG2 transcripts which was significantly lower in the lungs of asthmatics compared to normal subjects [ 42 ]. Therefore, as seen for the brain [ 43 , 44 ], the skin olfactory system might be affected under stress conditions.…”

Bioinformatics Analysis in Different Expression Genes and Potential Pathways of CD4+ Cells in Childhood Allergic Asthma

“…There are no current studies showing that these three genes are associated with asthma. However, a study in 2019 indicates that OR2AG2 from olfactory receptor family participates in the asthma pathogenesis and the suppression or genetic defects in OR2AG2 contribute to asthma pathogenesis [28]. According to the study, olfactory receptors express in the airways which is similar to bitter taste receptor [28].…”

“…However, a study in 2019 indicates that OR2AG2 from olfactory receptor family participates in the asthma pathogenesis and the suppression or genetic defects in OR2AG2 contribute to asthma pathogenesis [28]. According to the study, olfactory receptors express in the airways which is similar to bitter taste receptor [28]. Besides, another study shows that OR2AG1 (paralog of OR2AG2) and OR1D2 are functionally expressed in the in human airway smooth muscle cells (HASMCs) [29].…”

“…Besides, another study shows that OR2AG1 (paralog of OR2AG2) and OR1D2 are functionally expressed in the in human airway smooth muscle cells (HASMCs) [29]. These two olfactory receptor genes are activated by different ligands [30,31], which induce the brief increase of Ca2 + in HASMCs and both receptors can touch off cAMP-dependent signal transduction cascade [28]. CAMP possesses the ability to antagonize HASMC contraction and inhibits the cell proliferation, ghts the airway narrowing [32].…”

Comparison of statistical methods for recurrent event analysis using pediatrics asthma data

“…The present research article is based on the secondary data of a cohort study, 6‐8 where a cohort of 241 pediatric asthma patients (up to 18 y of age) was followed every third month and during acute exacerbation from August 2009 to December 2013 at the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. At enrollment and at each follow‐up visit, information on various variables was collected such as sociodemographic variables (at baseline only), family‐related variables (at baseline only), breastfeeding and feeding‐related variables (at baseline only), aggravating variables (at baseline only), asthmatic symptom variables (at baseline and each follow‐up visit), medication‐ and diagnosis‐related variables (at baseline and each follow‐up visit), and pulmonary function tests: spirometry and impulse‐oscillation‐system related variables (at baseline and each follow‐up visit).…”