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DNER – Type 2 Diabetes Mellitus

Two independent studies have strongly implicated DNER in the predisposition to type 2 diabetes mellitus. In a genome‑wide association study of American Indians, 278 young‑onset T2DM cases and 295 controls, along with 267 siblings used in family‑based analyses, a significant association of the rs1861612 C>T change in DNER was identified (odds ratio = 1.29 per T allele, P = 6.6 × 10⁻⁸) (PMID:24101674). In a separate study of a Chinese Han population with 298 T2DM patients and 500 controls, the same DNER rs1861612 variant was again found to increase disease risk, thereby replicating the initial association (PMID:25300688). Although classical segregation analysis is not available in these complex trait studies, the convergence of statistically robust genetic association signals from diverse populations substantiates the role of DNER.

The genetic evidence is bolstered by functional assays. In vitro transfection studies in murine pancreatic β‑cells have shown that DNER modulates notch signaling pathway gene expression, which is concordant with its proposed involvement in T2DM pathophysiology. Such functional data lend moderate experimental support to the genetic findings, suggesting that the DNER variant may affect beta‑cell function and thereby contribute to diabetes susceptibility.

Overall, the combined genetic and functional evidence supports a strong gene–disease association. While additional studies may further delineate the precise impact of DNER on T2DM risk, the current data are sufficient to inform diagnostic decision‑making, potential commercial assay development, and future publication efforts.

Key Take‑home: DNER is strongly associated with type 2 diabetes mellitus, providing a basis for its incorporation into clinical risk assessment models.

References

  • Diabetes • 2014 • A genome‑wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes mellitus PMID:24101674
  • Cell biochemistry and biophysics • 2015 • Association between single nucleotide polymorphisms of delta/notch‑like epidermal growth factor (EGF)‑related receptor (DNER) and Delta‑like 1 Ligand (DLL1) with the risk of type 2 diabetes mellitus in a Chinese Han population PMID:25300688

Evidence Based Scoring (AI generated)

Gene–Disease Association

Strong

Two independent association studies in diverse populations (>500 cases total) revealed a significant association of the rs1861612 C>T change with T2DM (PMID:24101674, PMID:25300688).

Genetic Evidence

Strong

Replication across American Indian and Chinese Han populations with robust p‑values and consistent allele effects support the genetic contribution of DNER to T2DM.

Functional Evidence

Moderate

Transfection studies in murine pancreatic β‑cells demonstrated that altered DNER expression affects notch signaling pathway genes, aligning with the human phenotype (PMID:24101674).