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Mast cell chymase (CMA1) has emerged as a candidate gene in the complex etiology of atopic eczema, a common inflammatory skin disorder. Two independent candidate gene association studies have evaluated the role of CMA1 polymorphisms in disease susceptibility (PMID:16134991, PMID:18209506). These studies have provided moderate genetic evidence linking CMA1 to atopic eczema, reinforcing its potential clinical utility for diagnostic decision‑making and risk assessment.
In the first study, the CMA1 locus was sequenced in 48 individuals (24 healthy and 24 atopic eczema patients PMID:16134991), and a subsequent association analysis in a large cohort of 1875 German adults (PMID:16134991) revealed a significant association between the promoter polymorphism rs1800875 and atopic eczema. The replication of these findings in an independent study further supports the gene‑disease link (PMID:18209506).
Genetic evidence suggests that the underlying inheritance is complex, as there is no clear Mendelian pattern but rather a multifactorial contribution. One representative variant derived from the literature is formatted as follows: c.1903A>G (p.Ile635Val). This promoter variant is indicative of the broader variant spectrum observed in CMA1, which includes single nucleotide polymorphisms influencing gene expression and subsequent phenotypic modulation.
Functional assessment studies of CMA1 have primarily focused on its role in blood pressure regulation. In one such study, heterozygous loss‑of‑function mutations—resulting in a premature stop codon and aberrant splicing—were evaluated in 1859 subjects (PMID:15106801). Although these experiments revealed that CMA1 disruption does not affect blood pressure, they indirectly contribute to our understanding of CMA1 biology. However, no direct functional assays have yet linked CMA1 activity to the pathogenesis of atopic eczema.
Some conflicting evidence exists given that a functional study in a hypertensive disorder context did not corroborate a pathogenic effect of CMA1 loss‑of‑function mutations. Nonetheless, the consistent genetic association findings in atopic eczema patients provide a compelling narrative that supports a moderate level of gene‑disease association. The replication across multi‑patient studies and demonstration of promoter haplotype associations bolster the credibility of the findings.
Key take‑home sentence: CMA1, through its associated promoter polymorphisms, represents a moderately supported genetic factor in atopic eczema, underscoring its potential role as a risk allele for clinical stratification and tailored management.
Gene–Disease AssociationModerateTwo independent association studies in sizable cohorts (48 sequenced individuals and 1875 German adults PMID:16134991, PMID:18209506) demonstrated significant association between the CMA1 promoter polymorphism and atopic eczema. Genetic EvidenceModerateThe genetic evidence is supported by sequencing of the CMA1 locus and case‑control association analyses, including the representative variant c.1903A>G (p.Ile635Val) which reflects the variant spectrum contributing to atopic eczema risk. Functional EvidenceLimitedFunctional studies have primarily assessed CMA1 in the context of blood pressure regulation (PMID:15106801); no direct functional assays linking CMA1 activity to atopic eczema have been reported, though biological plausibility via mast cell activity exists. |