Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
The association between OGA and type 2 diabetes mellitus is based on conflicting genetic evidence. In one study conducted in Mexican Americans (PMID:15793264), a novel intronic single nucleotide polymorphism in the OGA gene was found to be significantly associated with diabetes risk in 27 families comprising 436 individuals. This study demonstrated that the SNP accounted for approximately 25% of the linkage signal, suggesting a potential role for OGA in increasing disease susceptibility. However, another multi‐patient study in Pima Indians (PMID:12359146) detected two variants in OGA but observed no association with diabetes parameters in a cohort of roughly 1300 individuals.
The genetic evidence is therefore limited: a single positive association in one ethnic group contrasts with a negative replication in a larger cohort, and no specific coding variant meeting HGVS criteria has emerged from these studies. Moreover, while OGA’s enzymatic activity in removing O-linked β-N-acetylglucosamine is well characterized, functional studies directly linking abnormal OGA function to type 2 diabetes mellitus are lacking. This discordance underscores the need for additional replication and mechanistic investigations before OGA can be confidently integrated into diagnostic decision‑making or therapeutic strategies.
Key Take‑home sentence: Although a significant intronic SNP in OGA was linked to type 2 diabetes in Mexican Americans, conflicting findings and limited functional evidence necessitate further research to clarify its clinical utility.
Gene–Disease AssociationLimitedThe association is supported by a single positive study in Mexican Americans (27 families, 436 individuals [PMID:15793264]) showing significant association, contrasted by a negative study in approximately 1300 Pima Indians ([PMID:12359146]). Genetic EvidenceLimitedA significant intronic SNP was identified in one study; however, the lack of replication and absence of a clearly defined coding variant diminishes overall confidence in the genetic evidence. Functional EvidenceLimitedAlthough OGA’s enzymatic role in O-GlcNAc removal is well established, no direct functional assays have linked its dysregulation to type 2 diabetes mellitus. |