Low protective PON1 lactonase activity in an Arab population with high rates of coronary heart disease and diabetes

Background: Recent studies showing that high density lipoproteins (HDL) can effect plaque regression indicate that recent trial failures do not exclude an atheroprotective role of HDL. Instead, they highlight differences between HDL function and measured HDL-cholesterol (HDL-C). PON1 is one key functional activity of HDL. Urban Palestinians have lower HDL-C and a higher incidence and mortality of coronary heart disease than those of Israelis. We hypothesized that the cardioprotective PON1 lactonase and arylesterase activities and PON1 functional genotype may differ between Palestinians and Israelis. Methods: We measured PON1 activities in a cross-sectional population-based study of Palestinian (n = 960) and Israeli (n = 694) residents in Jerusalem, 1654 participants in all. Results: Palestinians had high prevalences of obesity and diabetes and low mean concentrations of HDL-cholesterol (0.97mmol/l in men and 1.19mmol/l in women). Lactonase and arylesterase activities were lower by 10.8% (p=1.2*10^-14) and 2.7% (p<0.0005), respectively, in Palestinians as compared to Israelis. The functional genotype distribution, demonstrated by plotting paraoxonase vs lactonase activities, showed a modest between-group difference (p=0.024), with 12.1% RR in Palestinian Arabs vs 8.4% in Israeli Jews, but no overall difference in allele frequencies. Lactonase correlated inversely with age (Spearman's rho=-156), weakly with BMI (-059), positively with HDL-C (173) and non-HDL-C (103), but was not associated with triglycerides or fasting glucose. Palestinians showed consistently lower lactonase activity in logistic regression models adjusted for multiple covariates and for functional genotype (odds ratios of 1.81 and 1.98, respectively, for the lower fifth vs the upper 4 fifths of lactonase activity p<0.0001). Conclusion: We showed a lower physiologically-significant lactonase PON1 activity in an Arab population, a finding consistent with the high cardiovascular and diabetes risk of Palestinians.