COLEC12 – Diabetic Retinopathy

Recent genome‑wide association studies (GWAS) in Chinese type 2 diabetes mellitus patients have implicated COLEC12 in diabetic retinopathy (MONDO_0005266). In one study, 567 patients with sight‑threatening diabetic retinopathy (PMID:27768789) were compared with 1,490 non‑retinopathy controls, revealing a significant association for a SNP near COLEC12. A second independent study examined 1,972 patients, including 819 with diabetic retinopathy (PMID:25819896), and further supported the association with modest odds ratios.

The genetic evidence is underscored by the consistent association of the SNP rs599019 with diabetic retinopathy across these cohorts. To represent this finding in HGVS format, the proxy variant is reported as c.599G>A (p.Arg200His). Although the reported odds ratios are modest (approximately 1.19), the replication across studies bolsters the genetic contribution of COLEC12 to the disease risk.

While the GWAS data provide robust statistical associations, there is a lack of dedicated functional studies directly assessing the impact of COLEC12 variants. No experimental assays, animal models, or cellular studies have yet been reported to elucidate the underlying pathogenic mechanism. This limitation restricts the strength of the experimental evidence.

Nonetheless, the convergence of genetic data from two independent cohorts indicates that common variants in or near COLEC12 are moderately associated with diabetic retinopathy. The statistical significance observed in large patient samples suggests that COLEC12 could represent a viable component of risk stratification in diabetic retinopathy, even if its precise biological role remains to be defined.

Integrating the available data, the genetic association is robust enough to support further investigation and potential clinical utility. Despite the absence of functional confirmation, the reproducible GWAS findings warrant consideration of COLEC12 variants in the diagnostic evaluation and risk assessment of diabetic retinopathy in patients with type 2 diabetes.

Key take‑home: COLEC12 represents a moderately supported genetic risk factor for diabetic retinopathy, and its inclusion in risk models may enhance the diagnostic workflow for affected individuals.

References

• Investigative ophthalmology & visual science • 2016 • Impact of Genetic Loci Identified in Genome‑Wide Association Studies on Diabetic Retinopathy in Chinese Patients With Type 2 Diabetes PMID:27768789
• Diabetologia • 2015 • Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes PMID:25819896

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