Factors Affecting Serum Paraoxonase 1 Activity in Migrant and Resident Gujarati South Asians

Paraoxonase 1 (PON1) protects against the development of atherosclerosis by hydrolysing damaging lipid peroxides formed in low-density lipoprotein (LDL) and cell membranes. The effect of migration on PON1 activity is unknown. We have investigated the effect of migration on serum PON1 activity by comparing an Indian Gujarati community who had migrated to Sandwell (West Midlands, UK) with people still living in their villages of origin around the town of Navsari (Gujarat, North-West India) and determined biochemical and nutritional parameters which may correlate with PON1 activity. PON1 activity was almost double in men and women living in Sandwell compared to those in Navsari. In the Spearman’s Rank correlation analysis, PON1 activity was significantly negatively correlated with fasting glucose and C-reactive protein, and positively with fasting non-esterified fatty acids, homeostasis model assessment (HOMA)-insulin sensitivity, and high-density lipoprotein (HDL) in rural Indian men, positively with HDL and apolipoprotein A1 (apo A1) in migrant Indian men, negatively with HOMA-β-cell activity and apo A1. It was positively correlated with HDL cholesterol, mean LDL particle diameter, and oxidised-LDL (ox-LDL) in rural Indian women and positively with HDL cholesterol, apo A1, and ox-LDL in migrant Indian women. Multivariate analysis with PON1 as the dependent variable indicated significant relationships with migrant status and HDL cholesterol only (both p<0.001). In conclusion, in the South Asian populations studied here, PON1 activity significantly correlated with measures of insulin sensitivity and the metabolic syndrome; however, by far the strongest determinant of PON1 activity was migration, or at least environmental and dietary changes which accompany migration. We also found an as yet unexplained lack of gender difference in HDL cholesterol, which requires further investigation.

[1]  S. Humphries,et al.  Paraoxonase-1 Is Not Associated with Coronary Artery Calcification in Type 2 Diabetes: Results from the PREDICT Study , 2012, Disease markers.

[2]  A. Koc,et al.  Paraoxonase and Arylesterase Activities in Children With Iron Deficiency Anemia and Vitamin B12 Deficiency Anemia , 2012, Pediatric hematology and oncology.

[3]  K. Gill,et al.  Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics. , 2012, Gene.

[4]  G. Rimbach,et al.  Determinants of paraoxonase 1 status: genes, drugs and nutrition. , 2011, Current medicinal chemistry.

[5]  Ferdinando Giacco,et al.  Oxidative stress and diabetic complications. , 2010, Circulation research.

[6]  J. Joven,et al.  Tissue distribution and expression of paraoxonases and chemokines in mouse: the ubiquitous and joint localisation suggest a systemic and coordinated role , 2010, Journal of Molecular Histology.

[7]  J. Joven,et al.  Serum paraoxonase-1 activity and genetic polymorphisms: common errors in measurement and interpretation of results , 2010, Clinical chemistry and laboratory medicine.

[8]  Hieronim Jakubowski,et al.  The role of paraoxonase 1 in the detoxification of homocysteine thiolactone. , 2010, Advances in experimental medicine and biology.

[9]  M. Sandhu,et al.  Both Paraoxonase-1 Genotype and Activity Do Not Predict the Risk of Future Coronary Artery Disease; the EPIC-Norfolk Prospective Population Study , 2009, PloS one.

[10]  Y. Ikeda,et al.  Low human paraoxonase predicts cardiovascular events in Japanese patients with type 2 diabetes , 2009, Acta Diabetologica.

[11]  Y. Ikeda,et al.  High glucose induces transactivation of the human paraoxonase 1 gene in hepatocytes. , 2008, Metabolism: clinical and experimental.

[12]  D. Shih,et al.  Is it just paraoxonase 1 or are other members of the paraoxonase gene family implicated in atherosclerosis? , 2008, Current opinion in lipidology.

[13]  T. Hayek,et al.  Paraoxonase 1 (PON1) attenuates diabetes development in mice through its antioxidative properties. , 2008, Free radical biology & medicine.

[14]  D. Arveiler,et al.  Paraoxonase activity and coronary heart disease risk in healthy middle-aged males: the PRIME study. , 2008, Atherosclerosis.

[15]  E. Topol,et al.  Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. , 2008, JAMA.

[16]  D. Shih,et al.  Adenovirus-Mediated Expression of Human Paraoxonase 3 Protects Against the Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[17]  M. Mackness,et al.  Defective Metabolism of Oxidized Phospholipid by HDL From People With Type 2 Diabetes , 2006, Diabetes.

[18]  D. Prabhakaran,et al.  Impact of migration on coronary heart disease risk factors: comparison of Gujaratis in Britain and their contemporaries in villages of origin in India. , 2006, Atherosclerosis.

[19]  D. Shih,et al.  Paraoxonase 1 (PON1) attenuates macrophage oxidative status: studies in PON1 transfected cells and in PON1 transgenic mice. , 2005, Atherosclerosis.

[20]  P. McElduff,et al.  Progestogens of varying androgenicity and cardiovascular risk factors in postmenopausal women receiving oestrogen replacement therapy , 2004, Clinical endocrinology.

[21]  P. McElduff,et al.  Low Paraoxonase Activity Predicts Coronary Events in the Caerphilly Prospective Study , 2003, Circulation.

[22]  P. Durrington,et al.  The paraoxonase gene family and coronary heart disease , 2002, Current opinion in lipidology.

[23]  BjörnFagerberg,et al.  Circulating Oxidized LDL Is Associated With Subclinical Atherosclerosis Development and Inflammatory Cytokines (AIR Study) , 2002 .

[24]  O. Kordonouri,et al.  Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus. , 2001, Metabolism: clinical and experimental.

[25]  J. Ferrières,et al.  Paraoxonase activity in two healthy populations with differing rates of coronary heart disease , 2000, European journal of clinical investigation.

[26]  B. La Du,et al.  Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. , 1999, Free radical biology & medicine.

[27]  B. La Du,et al.  The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. , 1996, Genomics.

[28]  P. Zimmet,et al.  Non‐insulin‐dependent Diabetes and 11‐Year Mortality in Asian Indian and Melanesian Fijians , 1996, Diabetic medicine : a journal of the British Diabetic Association.

[29]  A. Boulton,et al.  Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[30]  R. Balarajan Ethnicity and variations in the nation's health. , 1995, Health trends.

[31]  S. Adkins,et al.  Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. , 1993, American journal of human genetics.

[32]  D. Adler,et al.  The molecular basis of the human serum paraoxonase activity polymorphism , 1993, Nature Genetics.

[33]  A. Motulsky,et al.  Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon. , 1988, American journal of human genetics.

[34]  G. Siest,et al.  An improved method for phenotyping individuals for the human serum paraoxonase arylesterase polymorphism. , 1986, Annales de biologie clinique.

[35]  R. Krauss,et al.  Nondenaturing polyacrylamide gradient gel electrophoresis. , 1986, Methods in enzymology.

[36]  L. Bn,et al.  The polymorphic paraoxonase/arylesterase isozymes of human serum. , 1984 .

[37]  B. La Du,et al.  The human serum paraoxonase/arylesterase polymorphism. , 1983, American journal of human genetics.

[38]  D. Beevers,et al.  Heart attack, stroke, diabetes, and hypertension in West Indians, Asians, and whites in Birmingham, England. , 1980, British medical journal.