Association of PON2 variation with birth weight in Trinidadian neonates of South Asian ancestry

Busch, Christopher P.; Ramdath, D. Dan; Ramsewak, Samuel; Hegele, Robert A.

doi:10.1097/00008571-199906000-00010

Cited by 33 publications

(19 citation statements)

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“…We found no significant relationship between PON1 activity or PON1 genes and birth weight. Variations in the PON2 gene have been associated with low birth weight in Trinidadian neonates of South Asian but not African ancestry (Busch et al 1999). PON2 genes were not analyzed in our study.…”

Section: Discussionmentioning

confidence: 87%

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Berkowitz

Wetmur²,

Birman-Deych³

et al. 2004

Environ Health Perspect

307

261

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Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

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Section: Discussionmentioning

confidence: 87%

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Berkowitz

Wetmur²,

Birman-Deych³

et al. 2004

Environ Health Perspect

307

261

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“…There are two common polymorphisms of the PON2 gene, PON2–311 [C/G: Cys (C)/Ser (S)] and PON2–148 [C/G: Ala (A)/Gly (G)]. Some hypotypes of the PON2 gene have emerged to be novel risk factors for diseases such as CHD [49,50,51], hyperglycemia [52] and low birth weight [53]. The PON2 gene polymorphisms displayed a significant interracial distribution.…”

Section: Discussionmentioning

confidence: 99%

Study of the Relationship between Gene Polymorphisms of Paraoxonase 2 and Stroke in a Chinese Population

Yuan²,

Zhao³

et al. 2007

Cerebrovasc Dis

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Background and Purpose: The paraoxonase (PON) gene family has been demonstrated to be capable of preventing lipid peroxidation and could consequently exert antiatherosclerotic effects. Alteration of enzyme activity due to polymorphisms in the PON genes may influence the development of atheroma and thus affect stroke risk. PON2, the second member of this family, has twopolymorphisms, C311S and G148A. Our study explores the relationship between the two polymorphisms of PON2 and stroke. Methods: 120 healthy individuals, 150 patients with primary cerebral hemorrhage and 180 patients with cerebral infarction were included in this study. The genotypes of PON2 were detected with polymerase chain reaction and digested by specific restriction enzymes. Results: C311S and G148A polymorphisms of PON2 exist in Chinese people, with the allele frequencies 0.273/0.727 for C/S and 0.567/0.433 for G/A. No significant differences were observed in genotype and allele frequency between stroke patients and controls (p > 0.05). Conclusions: There was no significant correlation between the two tested polymorphisms of PON2 and stroke in the Chinese population. Allele C/S and G/A might not be independent risk factors for stroke.

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“…Although the expression of PON1 and PON3 is restricted primarily to the liver, PON2 is more widely expressed and is found in a number of tissues, including brain, liver, kidney, and testis (20). Furthermore, like PON1, PON2 polymorphisms are associated with numerous pathophysiological conditions, including variations in plasma lipoproteins (21,22), glucose levels in fasting type II diabetics (23), and neonatal birth weight (24) and the risk of coronary heart disease (25). Although a genetic association between PON2 and these conditions has been shown, the exact function of PON2 in humans is not known.…”

Section: Oxidation Of Low Density Lipoproteins (Ldl)mentioning

confidence: 99%

Paraoxonase-2 Is a Ubiquitously Expressed Protein with Antioxidant Properties and Is Capable of Preventing Cell-mediated Oxidative Modification of Low Density Lipoprotein

Ng¹,

Wadleigh²,

Gangopadhyay

et al. 2001

Journal of Biological Chemistry

419

402

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The oxidation of apolipoprotein B-containing lipoproteins and cell membrane lipids is believed to play an integral role in the development of fatty streak lesions, an initial step in atherogenesis. We have previously shown that two antioxidant-like enzymes, paraoxonase (PON)-1 and PON3, are high density lipoprotein-associated proteins capable of preventing the oxidative modification of low density lipoprotein (LDL) (Reddy, S. T., Wadleigh, D. J., Grijalva, V., Ng, C., Hama, S., Gangopadhyay, A., Shih, D. M., Lusis, A. J., Navab, M., and Fogelman, A. M. (2001) Arterioscler. Thromb. Vasc. Biol. 21, 542-547). In the present study, we demonstrate that PON2 (i) is not associated with high density lipoprotein; (ii) has antioxidant properties; and (iii) prevents LDL lipid peroxidation, reverses the oxidation of mildly oxidized LDL (MM-LDL), and inhibits the ability of MM-LDL to induce monocyte chemotaxis. The PON2 protein was overexpressed in HeLa cells using the tetracyclineinducible ("Tet-On") system, and its antioxidant capacity was measured in a fluorometric assay. Cells that overexpressed PON2 showed significantly less intracellular oxidative stress following treatment with hydrogen peroxide or oxidized phospholipid. Moreover, cells that overexpressed PON2 were also less effective in oxidizing and modifying LDL and, in fact, were able to reverse the effects of preformed MM-LDL. Our results suggest that PON2 possesses antioxidant properties similar to those of PON1 and PON3. However, in contrast to PON1 and PON3, PON2 may exert its antioxidant functions at the cellular level, joining the host of intracellular antioxidant enzymes that protect cells from oxidative stress. Oxidation of low density lipoproteins (LDL)1 trapped in the arterial subendothelial space is a key process in atherosclerotic lesion development. High density lipoprotein (HDL) inhibits LDL oxidation (1-4) and prevents the synthesis and secretion of monocyte chemotactic protein-1 by artery wall cells, thereby blocking the recruitment and transmigration of monocytes though the arterial endothelial layer (5). The anti-atherogenic properties associated with HDL are due, at least in part, to the activity of HDL-associated enzymes, which interact with LDL and prevent and/or reverse its oxidation (6). The calcium-dependent ester hydrolase paraoxonase (PON)-1 (EC 3.1.8.1) is one of several such enzymes and is found tightly associated with apoA-I in the HDL particle (7). Purified PON1 not only prevents LDL oxidation (8), but also blocks the ability of mildly oxidized LDL (MM-LDL) to induce monocyte chemotaxis and binding to endothelial cells (9). Epidemiological studies have shown that PON1 polymorphisms are correlated with variations in plasma lipoprotein levels (10) and coronary artery disease in some populations (11-15). In addition, Mackness et al. (16) showed that alloenzymes of PON1 determine the effectiveness of HDL in the protection of LDL from lipid peroxidation. Two other members of the PON gene family, termed PON2 and PON3, have been identified...

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Association of PON2 variation with birth weight in Trinidadian neonates of South Asian ancestry

Cited by 33 publications

References 0 publications

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Study of the Relationship between Gene Polymorphisms of Paraoxonase 2 and Stroke in a Chinese Population

Paraoxonase-2 Is a Ubiquitously Expressed Protein with Antioxidant Properties and Is Capable of Preventing Cell-mediated Oxidative Modification of Low Density Lipoprotein

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