부산대학교 도서관

Aims: The aim is to identify people with HNF1A‐MODY among individuals in diabetic cohort solely based on low hs‐CRP serum level and early diabetes onset. Methods: In 3537 participants, we analyzed the hs‐CRP levels. We analyzed the HNF1A gene in 50 participants (1.4% of the cohort) with type 1 or type 2 diabetes who had hs‐CRP ≤0.25 mg/L and were diagnosed with diabetes mellitus (DM) at the age of 8–40 years. We functionally characterized two identified missense variants. Results: Three participants had a rare variant in the HNF1A gene, two of which we classified as likely pathogenic: c.1369_1384dup (p.Val462Aspfs*92) and c.737T>G (p.Val246Gly), and one as likely benign: c.1573A>T (p.Thr525Ser). Our functional studies revealed that p.Val246Gly decreased HNF1α transactivation activity to ~59% and the DNA binding ability to ~16% of the wild‐type, while p.Thr525Ser variant showed no effect on transactivation activity, DNA binding, nor nuclear localization. Based on the two identified HNF1A‐MODY patients among 3537 people with diabetes, we estimate 0.057% as the minimal HNF1A‐MODY prevalence in Slovakia. A positive predictive value of hs‐CRP ≤0.25 mg/L for finding HNF1A‐MODY individuals was 4.0% (95% CI 0.7%, 13.5%). Conclusions: Hs‐CRP value and age of DM onset could be an alternative approach to current diagnostic criteria with a potential to increase the diagnostic rate of HNF1A‐MODY. [ABSTRACT FROM AUTHOR]