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The gene ZBED3 (HGNC:20711) has emerged as a candidate influencing type 2 diabetes mellitus (MONDO_0005148) risk through several large-scale genome‑wide association studies. Multiple independent cohorts, including a middle‑aged population study (PMID:21267535) and a Japanese case‑control analysis (PMID:22046406), consistently report modest but reproducible associations between common variants in or near ZBED3 and glucose homeostasis, underscoring the gene’s potential role in modulating insulin secretion and action.
The complex inheritance pattern of type 2 diabetes reflects a multifactorial etiology, with contributions from multiple loci, including ZBED3. Genetic associations identified in GWAS have been validated across diverse populations and meta‑analyses, reinforcing the reproducibility of the findings. Although no single causal variant in full HGVS nomenclature has been established for ZBED3, its recurring implication across independent studies supports its candidacy within the diabetes risk landscape.
Genetic evidence for ZBED3 is derived from large cohorts where risk alleles have been correlated with specific intermediate glycemic traits. While the GWAS approach has not yet pinpointed a unique coding change (i.e. a valid HGVS string for ZBED3), the cumulative association data from studies involving 5,722 participants (PMID:21267535) and replication in Japanese samples with nearly 5,000 participants (PMID:22046406) contribute to a robust overall association.
Functional evaluation studies have provided preliminary insights into the potential impact of ZBED3 on pancreatic beta‑cell function. In one functional assessment, novel variants within candidate diabetes genes including ZBED3 were observed in patients exhibiting beta‑cell failure, with suggestive functional trends toward altered insulin release (PMID:36585034). In parallel, in vitro analyses have noted pleiotropic effects on islet hormone secretion associated with common diabetes risk variants (PMID:23557703).
Despite the compelling genetic associations, functional studies remain at an early stage. The absence of clearly segregating familial variants specific to ZBED3 and the lack of a definitive causal coding change call for further mechanistic work. However, the convergent evidence from large diverse cohorts and preliminary functional assays lend credence to the role of ZBED3 in the pathogenesis of type 2 diabetes.
In summary, the integration of multi‑cohort GWAS data with early functional insights supports a strong gene‑disease association for ZBED3 in type 2 diabetes. This evidence underpins its potential utility for diagnostic decision‑making, commercial applications, and further academic investigation.
Gene–Disease AssociationStrongReplicated association across multiple large cohorts (PMID:21267535, PMID:22046406) and consistent effects on insulin secretion (PMID:23557703). Genetic EvidenceModerateGWAS analyses from diverse populations suggest a contribution of ZBED3 to type 2 diabetes susceptibility, despite the absence of a clearly delineated causal HGVS‑reported variant. Functional EvidenceLimitedPreliminary functional assessments indicate potential impairment of beta‑cell function associated with ZBED3 risk alleles, though further mechanistic validation is required (PMID:36585034). |