PTGDR2 rs538391: What Your Genotype Means
The genetic variant rs538391 is a common single-nucleotide polymorphism located in the PTGDR2 gene, which encodes the chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2). In immunogenetic research, this regulatory variant has been studied for its potential links to eosinophilic airway inflammation and asthma susceptibility. Overall, evidence supporting a definitive clinical effect remains limited and largely restricted to specific population subsets.
What each genotype means
Typical airway inflammation risk
You carry two copies of the common G allele at rs538391 in the PTGDR2 (CRTH2) gene. Published studies associate this baseline genotype with standard levels of PTGDR2 expression and baseline population risk for allergic airway inflammation and asthma. Because clinical evidence remains limited and asthma risk is influenced by many genes and environmental factors, this result alone does not indicate protection or vulnerability.
Found in approximately 55% to 65% of individuals of European ancestry and roughly 70% to 75% of East Asian populations.
Slightly altered asthma susceptibility
You carry one copy of the A allele and one copy of the G allele at rs538391. Candidate-gene research has linked the minor A allele to altered transcriptional regulation of the PTGDR2 receptor, with modest associations observed for eosinophilic airway activation and asthma susceptibility. However, evidence is limited, results across diverse ancestries are mixed, and carrying this genotype does not diagnose any respiratory condition.
Carried by approximately 30% to 38% of individuals in European populations and roughly 25% of individuals of East Asian ancestry.
Modestly altered asthma susceptibility
You carry two copies of the minor A allele at rs538391 in the PTGDR2 gene. Some association studies have linked homozygosity for this regulatory variant to differences in CRTH2 expression and altered susceptibility to allergic inflammation or asthma. However, published clinical evidence remains limited and overall risk depends heavily on wider polygenic patterns and environmental exposures.
Found in roughly 4% to 6% of European populations and approximately 2% of East Asian populations.
What Is rs538391 and Where Is It Located?
The single nucleotide polymorphism rs538391 is a regulatory genetic variant situated within the human PTGDR2 gene on chromosome 14. PTGDR2, historically and widely known as CRTH2 or CD294, plays a central role in guiding immune responses. The rs538391 variant represents a single base-pair substitution (commonly C and T alleles) located in the regulatory untranslated region of the gene rather than within the protein-coding sequence itself. Consequently, this variant does not alter the underlying amino acid sequence of the receptor protein. Instead, laboratory and genomic investigations suggest that regulatory polymorphisms in this genomic region can influence messenger RNA stability, transcriptional activity, and the overall expression levels of the receptor on circulating immune cells. Because it acts primarily as an expression quantitative trait locus or fine-tuning regulatory switch, its individual influence on complex traits is subtle and subject to modulation by other genetic variants and environmental exposures.
The Biological Role of PTGDR2 and CRTH2
The PTGDR2 gene encodes prostaglandin D2 receptor 2, a critical G-protein-coupled receptor predominantly expressed on key effector cells of type 2 allergic inflammation, including T helper type 2 (Th2) lymphocytes, eosinophils, and basophils. When tissues encounter allergens, mast cells release prostaglandin D2 (PGD2), an inflammatory lipid mediator. PGD2 binds to PTGDR2, initiating intracellular signaling cascades that trigger cell migration, induce calcium mobilization, and prevent the programmed death of inflammatory cells. Through this receptor pathway, activated eosinophils and basophils are recruited directly to mucosal tissues such as the bronchial epithelium and skin. Because of its pivotal placement at the intersection of innate and adaptive allergic immune cascades, PTGDR2 has garnered considerable pharmaceutical interest as a therapeutic target for selective small-molecule antagonists designed to mitigate severe eosinophilic asthma and chronic rhinosinusitis.
Research Associations and Scientific Evidence
Multiple candidate gene association studies and functional assays have evaluated whether polymorphisms in the 3' untranslated region of PTGDR2, including rs538391, modulate individual susceptibility to respiratory conditions such as asthma. Some published cohorts have reported modest statistical associations between the minor allele and increased eosinophilic airway activation, altered peripheral blood receptor expression, or elevated risk of developing allergic asthma. However, the scientific evidence supporting rs538391 remains classified as limited. Large-scale genome-wide association studies (GWAS) have demonstrated that susceptibility to asthma and allergic diseases is driven by hundreds of distributed loci, each conferring small fractional changes in risk. Findings for rs538391 have occasionally varied across ancestral backgrounds, and isolated statistical signals have not consistently reached stringent genome-wide significance thresholds. As a result, rs538391 is best considered a research-grade marker of immune regulation rather than a high-penetrance risk factor.
How Common Is rs538391 Across Populations?
Data from large genomic aggregation resources, including the 1000 Genomes Project and gnomAD, indicate that rs538391 is a common variant across human populations, though its allele distribution exhibits noticeable geographic variation. The minor allele displays an estimated frequency of approximately 0.15 (15%) in individuals of East Asian ancestry. In contrast, in populations of European ancestry, the minor allele frequency is typically higher, ranging between 0.20 and 0.25 (20% to 25%). Homozygotes for the reference allele represent the vast majority in most surveyed groups, while heterozygotes form a substantial minority and homozygotes for the minor allele occur in roughly 2% to 6% of people depending on ancestry. Because this variant is widely distributed among millions of healthy individuals worldwide without any manifestation of respiratory illness, carrying the minor allele is clearly neither necessary nor sufficient to trigger allergic disease.
What You Can and Cannot Do With This Information
Understanding your rs538391 genotype provides an educational glimpse into how subtle genetic variations influence the biological pathways of the immune system, but it cannot be used as a standalone diagnostic tool. Possessing a putative susceptibility allele does not mean you will develop asthma, nor does having a reference genotype protect you from environmental allergies. Environmental determinants—such as viral exposures, airborne allergens, microbiome diversity, and tobacco smoke—exert profound influences on respiratory outcomes that outweigh the minor statistical effect of any single regulatory variant. Furthermore, genetic testing for rs538391 should never guide medication choices. If you manage asthma, chronic allergies, or other inflammatory conditions, you should always discuss your symptoms, treatment plan, and prescription dosages directly with a qualified clinician or allergy specialist.
How common is this variant?
The minor allele occurs at an estimated frequency of approximately 0.15 in East Asian populations and between 0.20 and 0.25 in European populations, making both heterozygous and homozygous states common globally.
Frequently asked questions
Does having the rs538391 minor allele mean I will develop asthma?
No. Carrying the minor allele at rs538391 is only weakly associated with statistical variations in airway inflammation in population studies. Asthma is a complex, multifactorial condition influenced by hundreds of genetic factors and diverse environmental triggers, meaning most carriers never develop the condition.
What is the function of the PTGDR2 (CRTH2) gene?
PTGDR2 encodes a G-protein-coupled receptor activated by prostaglandin D2 that orchestrates the movement and activation of immune cells involved in allergic responses, such as Th2 lymphocytes, basophils, and eosinophils.
Can this genetic test determine which allergy medications I should take?
No, rs538391 testing is not approved for pharmacogenomic decision-making. You should never initiate, alter, or stop any asthma or allergy medications based on this genetic result without consulting your prescribing healthcare provider or pharmacist.
Why is the evidence for rs538391 categorized as limited?
While targeted candidate gene studies have noted modest associations with respiratory traits, findings have not consistently met stringent thresholds across large-scale genome-wide association studies, and effect sizes vary considerably among different ancestral populations.
Sources & further reading
Educational information only, last refreshed 9/13/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Variant in the PTGDR2 (CRTH2) gene associated with allergic disease susceptibility.
This variant is associated with allergic inflammation and Th2-mediated immune responses.
A polymorphism in the CRTh2 gene linked to various allergic phenotypes in diverse populations.
This variant in the CRTh2 receptor gene is associated with susceptibility to allergic asthma and altered receptor expression levels.