AUTHOR=Shrestha Palikhe Nami , Mackenzie Constance A. , Licskai Christopher , Kim Richard B. , Vliagoftis Harissios , Cameron Lisa 

TITLE=The CRTh2 polymorphism rs533116 G > A associates with asthma severity in older females

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.970495

DOI=10.3389/fmed.2022.970495

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>CRTh2 is G protein coupled receptor for prostaglandin D2 (PGD)<sub>2</sub> expressed by immune cells that drive type 2 inflammation such as CD4<sup>+</sup> T cells (Th2), eosinophils and group 2 innate lymphoid cells (ILC2) as well as structural cells including smooth muscle and epithelium. CRTh2-expressing cells are increased in the blood and airways of asthmatics and severe asthma is characterized by increased activity of the PGD<sub>2</sub>-CRTh2 pathway. The <italic>CRTh2</italic> single nucleotide polymorphism (SNP) rs533116 G &gt; A is associated with development of asthma and increased Th2 cell differentiation.</p></sec><sec><title>Objective</title><p>To examine whether CRTh2 rs533116G &gt; A associates with asthma severity. Since severe asthma is more common in females than males, we performed a sex-stratified analysis.</p></sec><sec><title>Methods</title><p>Clinical data from asthmatics (<italic>n</italic> = 170) were obtained from clinic visits and chart review. Asthma severity was assessed according to ERS/ATS guidelines. Peripheral blood cells were characterized by flow cytometry and qRT-PCR. Genotyping was performed by TaqMan assay.</p></sec><sec><title>Results</title><p>Older females (≥45 years) homozygous for minor A allele of rs533116 were more likely to have severe asthma, lower FEV<sub>1</sub>, a higher prescribed dose of inhaled corticosteroid and more type 2 inflammation than females carrying GA or GG genotypes. Comparing females and males with the AA genotype also revealed that women had more type 2 inflammation.</p></sec><sec><title>Conclusions and significance</title><p>The polymorphism CRTh2 rs533116 G &gt; A associates with severe asthma and type 2 inflammation in older females. This study reveals a gene-sex-aging interaction influencing the effect of CRTh2 on asthma severity.</p></sec>