To investigate the relationship between PON1 genetic variation, serum paraoxonase activity, and dysmetabolic phenotypes.
Approach:
Cohort Analysis: Analyzed 922 individuals from the PREVADIAB2 cohort to assess genetic determinants of PONase activity and their associations with dysglycemia and metabolic liver risk.
Genetic Variant Identification: Identified independent PON1 variants through genome-wide analysis and combined them into haplotypes for further association studies.
Key Findings:
Two independent PON1 variants, rs2057681 and rs854572, were identified as major determinants of PONase activity.
Haplotype analysis revealed that specific genetic configurations were associated with dysglycemia and metabolic liver risk in a genotype-dependent manner, with varying effects based on the genetic background of individuals.
Despite strong genetic effects on PONase activity, enzyme activity itself was not directly associated with dysmetabolic phenotypes.
Interpretation:
PON1 genetic architecture is associated with dysglycemia and metabolic liver risk beyond enzyme activity.
Limitations:
The study is limited to a specific cohort, which may affect the generalizability of the findings.
Potential confounding factors in the assessment of metabolic risk were not fully explored.
Conclusion:
The findings provide insight into the genetic regulation of metabolic risk and may help explain inconsistent associations of PON1 variants in cardiometabolic disease.
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
