Paraoxonase promoter polymorphism T(-107)C and relative paraoxonase deficiency as determinants of risk of coronary artery disease

This study tested the hypothesis that promoter polymorphism T(-107)C of the human paraoxonase gene (PON1) is associated with risk of coronary disease. Participants (n=897) were recruited from a cardiology department. All unde rwent coronary arteriography and were defined as coronary artery disease po sitive (n=699) or negative (n=198). No association of the promoter genotype s with coronary disease was observed in the overall population, but the hig h expressor genotype (-107CC) was associated with decreased risk of disease in patients aged 60 years or under in univariate and multivariate analysis independently of established risk factors. A significant deficiency in par aoxonase relative to cholesterol was apparent in patients, even when they w ere matched with controls for total and low-density lipoprotein cholesterol levels. The -107 polymorphism was not associated with risk in older patien ts (61 years or over). Age was negatively associated with serum concentrati ons and activities of paraoxonase; serum paraoxonase was significantly high er in those aged under 61 years than in those aged 61 or over. Age was an i ndependent predictor of paraoxonase concentrations. The results indicate th at in this population of patients the promoter polymorphism T(-107)C of the PON1 gene is an independent risk factor for coronary disease in those 60 y ears or younger. The data are consistent with the hypothesis that lower exp ression of this anti-oxidant enzyme increases risk of coronary disease. Age ing has also been identified as an independent determinant of serum paraoxo nase levels. Ageing is correlated with reduced serum paraoxonase levels, wh ich may compromise the protective influence of enzyme. The results are cons istent with the contention that the protective, anti-oxidant capacity of hi gh density lipoproteins is at least in part genetically determined.