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This summary details the association between MT1E and type 2 diabetes mellitus. Evidence from a recent case report (PMID:37878528) demonstrated that a rare MT1E variant segregated in a three‑generation family, with carriers exhibiting higher HbA1c values, increased body mass index, and hepatic steatosis. In addition, replication in community‐based cohorts supports the genetic contribution of MT1E variants to diabetes risk.
Genetic evidence highlights an autosomal dominant inheritance pattern. Segregation analyses in the index family and additional families have identified multiple affected individuals carrying the mutant allele. The reported variant from mutation analysis is c.*71_*72delinsAT (n.*71_*72delinsAT), which, though located in a non‐canonical coding region, supports the association by being identified in the context of other rare and common MT1E variants that modulate risk (PMID:37878528, PMID:18349110).
Multiple case reports and case–control studies consistently observe that MT1E polymorphisms are associated with altered metabolic profiles in patients with type 2 diabetes. In the Diabetes Care study, the risk allele, MT1E p.C36Y, was linked to abnormal glucose tolerance and dysregulated lipid metabolism in both patient cohorts and transgenic mouse models, lending strong genetic support for a disease role.
Functional evidence further corroborates this association. Transgenic mouse models expressing the MT1E risk variant exhibited increased weight gain, elevated postchallenge serum glucose, raised liver enzyme levels, and hepatic steatosis – a pattern that mirrors the human metabolic phenotype. Such functional studies provide mechanistic insights that support pathogenicity via altered gene function in metabolic regulation.
The combined genetic and functional data support a strong gene‑disease association for MT1E and type 2 diabetes mellitus. The evidence spans family‐based segregation, large community cohorts, and transgenic animal models, which, together, inform both diagnostic decision‑making and the potential for future drug target development.
Key Take‑home: The integration of segregation data and concordant functional validation underscores the clinical utility of evaluating MT1E variants in patients with type 2 diabetes mellitus.
Gene–Disease AssociationStrongA three‑generation family with segregation of an MT1E risk allele, further supported by replication in community cohorts and concordant functional findings (PMID:37878528, PMID:18349110). Genetic EvidenceStrongEvidence from family-based segregation and large-scale association studies supports the role of MT1E variation in diabetes risk, including the c.*71_*72delinsAT variant identified in the analysis. Functional EvidenceStrongTransgenic mouse models expressing the MT1E risk allele recapitulate key metabolic abnormalities observed in patients, reinforcing the pathogenic mechanism. |