title: Low protective PON1 lactonase activity in an Arab population with high rates of coronary heart disease and diabetes.
abstract: 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 (0.97 mmol/l in men and 1.19 mmol/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).
  
  
  CONCLUSIONS
  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.
authors: Glycation, Oxidation and Disease Laboratory, Department of Research, College of Osteopathic Medicine, Touro University California, Vallejo, CA, United States. Electronic address: alejandro.gugliucci@tu.edu.
authors: A
authors: A
authors: Gugliucci
authors: Glycation, Oxidation and Disease Laboratory, Department of Research, College of Osteopathic Medicine, Touro University California, Vallejo, CA, United States.
authors: R
authors: R
authors: Caccavello
authors: Dept of Cardiology, Hadassah Medical Center, Ein Kerem, Jerusalem, Israel; St Joseph Hospital, Jerusalem, Israel.
authors: H
authors: H
authors: Nassar
authors: Hebrew University, Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel.
authors: W
authors: W
authors: Abu Ahmad
authors: Hebrew University, Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel.
authors: R
authors: R
authors: Sinnreich
authors: Hebrew University, Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel.
authors: J D
authors: JD
authors: Kark
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D018912:Arabs; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000235:genetics* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D003327:Coronary Disease / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Cardiovascular risk; High-density lipoprotein; Jewish; Lactonase; PON1; Palestinians