Paraoxonase-1 (PON1) promoter region polymorphisms, serum PON1 status and coronary heart disease

Introduction: Serum paraoxonase-1 (PON1) retards the oxidation of low-density lipoprotein and cell membranes and is atheroprotective. Polymorphisms in the promoter region of the PON1 gene have been shown to affect serum PON1 levels and have been related to the presence of coronary heart disease (CHD) in some studies. However, contradictory results have been reported with regard to promoter region polymorphisms and CHD presence; therefore we have re-examined the effects of the C-108T and G-909C promoter polymorphisms on PON1 levels and the presence of CHD in a large case-control study. Material and methods: Paraoxonase-1 activity, concentration and the C-108T and G-909C polymorphisms were measured in 417 people with CHD and 282 healthy controls, in a case control study. Results: Paraoxonase-1 activity and concentration were significantly lower in the CHD population compared to controls regardless of their C-108T and G-909C genotype (p < 0.001). Paraoxonase-1 activity was significantly different in the C-108T genotypes in both the control and CHD groups in the order TT GC > CC (p < 0.01). Haplotype analysis revealed no consistent patterns of PON1 activity in the CHD population; however, in the controls PON1 activity differed between haplotypes GGCC>GGTC>GGTT (p < 0.05) and GCCC > GCTC > GCTT (p < 0.02). Neither promoter polymorphism was associated with CHD presence. Conclusions: Paraoxonase-1 status was significantly lower in people with CHD and was affected by the promoter region polymorphisms.