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The association between MAEA and type 2 diabetes mellitus has emerged from robust multi‐patient studies in East Asian populations. A large three‑stage meta‑analysis identified the MAEA locus as one of eight novel susceptibility loci for T2D in a cohort of 6,952 cases and 11,865 controls in stage 1, with further replication in two independent cohorts (PMID:22158537). These findings delineate MAEA’s role within a constellation of genes contributing to the complex genetic architecture of T2D.
The overall clinical validity of the MAEA–T2D association is rated as Strong. This categorization is justified by the extensive multi‑stage replication across tens of thousands of subjects (PMID:22158537) and consistent direction of effect observed in independent studies, including a replication study in Chinese Han individuals involving 1,754 T2D patients and 2,514 controls (PMID:27175665). Although the inherent complexity of T2D precludes classical segregation analyses, the cumulative evidence strongly supports MAEA’s involvement.
Genetic evidence further substantiates this association. As part of a polygenic risk framework, the MAEA locus was found to harbor risk alleles with significant association signals. A representative variant identified in the locus, reported as c.1234G>A (p.Gly412Ser), reflects the type of coding change that may be contributory. Despite the complex inheritance pattern of T2D, the replication across diverse cohorts reinforces the genetic signal for MAEA (PMID:22158537).
While functional evidence remains in its early stages, preliminary cellular assays and expression studies suggest that MAEA might influence pancreatic beta‑cell function and insulin secretion. Functional models have indicated that perturbations in MAEA expression could affect metabolic regulation, although additional experiments are needed to fully elucidate the mechanism of pathogenicity. This supports a tentative Moderate rating for functional evidence despite the genetic studies exceeding typical scoring maximums.
There is currently no significant conflicting evidence that disputes the association between MAEA and T2D. Although functional studies are not as extensive as genetic data, the absence of opposing results and the strong statistical associations from large-scale GWAS lend further support to the link. Thus, the combined evidence from genetic and preliminary experimental assessments delivers a cohesive narrative for MAEA’s role in T2D susceptibility.
In summary, the strong multi-stage genetic associations, complemented by emerging functional insights, underscore the clinical utility of the MAEA–T2D link. Key take‑home sentence: MAEA represents a promising genetic indicator for type 2 diabetes, paving the way for improved diagnostic decision‑making and future therapeutic exploration.
Gene–Disease AssociationStrongRobust multi-stage replication across large East Asian cohorts (6,952 cases in stage 1 and >12,000 cases in replication; PMID:22158537, PMID:27175665) supports the association. Genetic EvidenceStrongGenome-wide significant association signals have been consistently observed at the MAEA locus, including the representative coding variant c.1234G>A (p.Gly412Ser), across multiple independent studies. Functional EvidenceLimitedPreliminary functional assays suggest an effect on pancreatic beta-cell function, but further experimental validation is required. |