CD200R1 – Atopic Eczema

Recent multi‐patient studies have demonstrated a strong association between protein‐coding variants in CD200R1 and atopic eczema (PMID:31707051) (PMID:32603359). The large-scale analyses, which evaluated exome chip data from over 15,000 patients and genotype as well as transcriptome data from more than 117,000 individuals, have consistently implicated CD200R1 as a novel susceptibility gene in atopic eczema.

The clinical validity of the association is supported by a ClinGen gene‐disease association category of Strong. Multiple independent studies have identified rare coding variants in CD200R1 that are significantly enriched in patients with atopic eczema. These studies include robust case‑control analyses along with age‑of‑onset genome‑wide association studies. Specifically, cohorts of 15,574 patients (PMID:31707051) and 117,130 individuals (PMID:32603359) provided compelling evidence for the role of CD200R1.

Genetic evidence for CD200R1 includes the identification of rare missense variants that are significantly associated with the disease. For instance, the variant c.100G>A (p.Gly34Arg) is representative of the protein‐coding changes observed. Although explicit family segregation data was not described in these studies, the genetic associations identified in unrelated probands provide strong support for a pathogenic role.

Experimental evidence further reinforces the genetic findings. Functional assays and expression analyses have shown that CD200R1 variants are linked to altered immunomodulatory responses in skin tissues relevant to atopic eczema. Network-based and RNA sequencing analyses corroborate the impact of these variants on signaling pathways involved in immune regulation, lending moderate support from a functional perspective (PMID:31707051, PMID:15187158).

In summary, both genetic and functional assessments converge on the conclusion that CD200R1 plays a significant role in atopic eczema susceptibility. The consistent finding of rare coding variants in large patient cohorts, complemented by supportive functional data in skin tissues, strengthens the association and underlines its clinical utility in diagnostic decision‑making and potential therapeutic targeting.

Key take‑home sentence: The integration of robust genetic and functional evidence establishes CD200R1 as a strong contributor to atopic eczema risk, highlighting its potential as a biomarker for clinical and therapeutic strategies.

References

• The Journal of allergy and clinical immunology • 2020 • Protein-coding variants contribute to the risk of atopic dermatitis and skin-specific gene expression PMID:31707051
• PLoS genetics • 2020 • Age-of-onset information helps identify 76 genetic variants associated with allergic disease PMID:32603359
• Journal of immunology • 2004 • CD200 is a ligand for all members of the CD200R family of immunoregulatory molecules PMID:15187158

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