NOX3 – Type 2 Diabetes Mellitus

Recent multi‑patient studies have reported an association between NOX3 and type 2 diabetes mellitus. In one study, gene expression profiling of peripheral blood mononuclear cells from diabetic individuals in 20 Mexican American families implicated NOX3 among six well‐annotated genes related to blood pressure dynamics in type 2 diabetes mellitus (PMID:27980621). A subsequent time‑to‑event GWAS of 49,230 participants with type 2 diabetes mellitus further revealed that an intergenic variant between TFB1M and NOX3 reached genome‑wide significance in patients developing cardiovascular complications (PMID:37546893).

Despite the large cohorts and consistent association signals, the overall genetic evidence remains limited because no pathogenic variants have been definitively segregated and there is a lack of direct functional validation for a disease‐causing mechanism in type 2 diabetes mellitus. The genetic evidence relies on statistically significant association signals rather than classical segregation or experimental studies showing a role for NOX3 in disease pathogenesis. Key take‑home: Although preliminary associations with type 2 diabetes mellitus are promising, additional studies are needed to firmly establish the clinical utility of NOX3 for diagnostic decision‑making in this context.

References

• BMC proceedings • 2016 • Analysis of gene expression to predict dynamics of future hypertension incidence in type 2 diabetic patients PMID:27980621
• medRxiv • 2023 • Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People with Type 2 Diabetes Mellitus PMID:37546893

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