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Recent studies have examined the association between variants in CCL1 (HGNC:10609) and chronic obstructive pulmonary disease (MONDO_0005002). In a retrospective analysis of a cohort of 276 male patients (PMID:16864713), a single nucleotide polymorphism located in the predicted enhancer region of CCL1 (rs2282691) was significantly associated with an increased frequency and severity of acute exacerbations of COPD under a dominant model. Although a standardized coding variant (c. notation) was not reported in these studies, the genetic data suggest that regulatory variation in CCL1 may contribute to disease risk.
Functional assessment further supports the biological relevance of CCL1 in COPD pathogenesis. An electromobility shift assay demonstrated that the transcription factor C/EBPβ binds selectively to the T allele rather than the A allele, indicating an allele-dependent regulatory mechanism that could influence the inflammatory response in pulmonary tissues (PMID:16864713). Conversely, an independent study evaluating multiple proinflammatory cytokine genes did not find a significant impact of these alleles on plasma protein levels (PMID:30296713), introducing some conflicting evidence. Overall, while there is limited genetic and experimental support for the association of CCL1 with COPD, the observed dominant effect on acute exacerbations and the functional insights into transcription factor binding provide a basis for further investigation. Key take‑home: Current evidence suggests a potential, though limited, role for CCL1 regulatory variation in modifying COPD risk, underscoring the need for additional studies before clinical implementation.
Gene–Disease AssociationLimitedRetrospective and prospective analysis in a cohort of 276 patients showed a significant dominant association of a CCL1 enhancer SNP with acute COPD exacerbations (PMID:16864713), but conflicting results regarding cytokine levels in an independent study (PMID:30296713) limit the evidence strength. Genetic EvidenceLimitedThe association is supported by statistically significant findings for a SNP in CCL1; however, the lack of standardized coding (c.) variant reporting and additional segregation data restricts the genetic evidence. Functional EvidenceModerateAllele-specific binding of C/EBPβ in electromobility shift assays supports a regulatory mechanism in lung tissue (PMID:16864713), although discrepancies in cytokine expression studies suggest that further validation is needed. |