PON1 haplotypes show genotype-dependent associations with dysglycemia and metabolic liver risk beyond paraoxonase activity
By
Laura Batista-Herrera
Maria João Meneses
Rogério T. Ribeiro
Luís Gardete-Correia
João F. Raposo
José Manuel Boavida
Carlos Penha-Gonçalves
Maria Paula Macedo
July 7, 2026
Clinical Scorecard: Genetic Variants of PON1 Exhibit Associations with Dysglycemia and Metabolic Liver Risk Beyond Enzyme Activity
At a Glance
Category Detail
Condition Dysglycemia and Metabolic Liver Risk Key Mechanisms Genetic variation in PON1 influences enzyme activity and is associated with dysglycemia and metabolic liver risk beyond enzymatic activity. Target Population Individuals aged >55 years from the PREVADIAB2 cohort. Care Setting Population-based cohort study.
Key Highlights
Two PON1 variants (rs2057681 and rs854572) identified as major determinants of PONase activity. Haplotype analysis shows genotype-dependent associations with dysglycemia and metabolic liver risk. Despite strong genetic effects on PONase activity, enzyme activity was not directly associated with dysmetabolic phenotypes. Guideline-Based Recommendations
Diagnosis
Glycemic status defined according to WHO/International Diabetes Federation criteria. Management
Monitoring & Follow-up
Use of the Fibrotic NASH Index (FNI) to estimate metabolic liver risk. Risks
Increased risk of dysglycemia and metabolic liver risk associated with specific PON1 genetic configurations. Patient & Prescribing Data
Individuals aged >55 years with genetic variations in PON1.
Understanding genetic variations may inform risk assessment for dysglycemia and metabolic liver disease.
Clinical Best Practices
Consider genetic testing for PON1 variants in patients at risk for dysglycemia and metabolic liver disease. Monitor glycemic status and metabolic liver risk using established scoring tools. Related Resources & Content
