Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration

Baird, Paul N.; Chu, Diep; Guida, Elizabeth; Vu, Hien; Guymer, Robyn H.

doi:10.1016/j.ajo.2004.04.053

Cited by 37 publications

(20 citation statements)

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“…PON1 has an equally broad infl uence on human health, having been linked to vascular disease, Parkinson's disease ( 57-59 ), systemic lupus erythematosus ( 60-62 ), breast cancer ( 63, 64 ), age-related macular degeneration (65)(66)(67)(68)(69)(70)(71), and diabetes ( 36, 37 ) among other disorders. A fuller understanding of the determinants of PON1 activity should include the effects of diet.…”

Section: Discussionmentioning

confidence: 99%

Dietary cholesterol increases paraoxonase 1 enzyme activity

Kim

Burt

Ranchalis

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org High density lipoprotein (HDL) levels have long believed to be cardioprotective ( 1 ) through a variety of processes, including reverse cholesterol transport in which excess cholesterol is taken to the liver for excretion ( 2 ). However, recent studies have highlighted the need to better understand the cardioprotective role of HDL. For example, two recent Mendelian randomization studies found that single nucleotide polymorphisms (SNP) that predict plasma HDL cholesterol (HDL-C) variance were not associated with myocardial infarction (MI) ( 3, 4 ). Moreover, a recent drug trial with torcetrapib, a cholesterol ester transport protein inhibitor, found that although torcetrapib increased levels of HDL and lowered deleterious low density lipoprotein (LDL) levels, it did not affect atherosclerotic measures and paradoxically led to an increase in adverse cardiovascular events ( 5 ). In addition, a recent large randomized clinical trial did not show a benefi t of niacin in preventing adverse cardiovascular outcomes, despite improved levels of HDL-C and triglycerides in the treatment group ( 6 ). These results refocus attention on the many aspects of HDL biology that are not captured by serum measurements of HDL, such as its paraoxonase 1 (PON1) activity, which itself is inversely associated with cardiovascular and other human diseases.The activity of PON1 , a liver-produced glycoprotein enzyme bound to the surface of HDL, is consistently correlated with atherosclerotic vascular disease and end-organ damage ( 7-9 ). PON1 is at least partially responsible for the cardioprotective inhibitory effects of HDL on LDL peroxidation ( 10-12 ), and it also has been demonstrated to hydrolyze oxidized lipid or lipid hydroperoxides in LDL ( 13 ). Inactivation of PON1 reduced the ability of HDL to Abstract HDL-associated paraoxonase 1 (PON1) activity has been consistently associated with cardiovascular and other diseases. Vitamins C and E intake have previously been positively associated with PON1 in a subset of the Carotid Lesion Epidemiology and Risk (CLEAR) cohort. The goal of this study was to replicate these fi ndings and determine whether other nutrient intake affected PON1 activity. To predict nutrient and mineral intake values, 1,402 subjects completed a standardized food frequency survey of their dietary habits over the past year. Stepwise regression was used to evaluate dietary and covariate effects on PON1 arylesterase activity. Five dietary components, cholesterol ( P < 2.0 × 10 ؊ 16 ), alcohol ( P = 8.51 × 10 ؊ 8 ), vitamin C ( P = 7.97 × 10 ؊ 5 ), iron ( P = 0.0026), and folic acid (0.037) were independently predictive of PON1 activity. Dietary cholesterol was positively associated and predicted 5.5% of PON1 activity, second in variance explained. This study presents a novel fi nding of dietary cholesterol, iron, and folic acid predicting PON1 activity in humans and confi rms prior reported associations, including that with vitamin C. Identifying and understanding en...

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Section: Discussionmentioning

confidence: 99%

Dietary cholesterol increases paraoxonase 1 enzyme activity

Kim

Burt

Ranchalis

et al. 2012

Journal of Lipid Research

View full text Add to dashboard Cite

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“…Given that SNPs in PON2 have been previously reported in this cohort to predict PON1 enzyme activity, the failure of additional PON2 SNPs to predict PON1 activity in SKAT analyses may and the quorum-sensing factor of pseudomonas aeruginosa ( 35,36 ). Perhaps due to this extensive substrate specifi city, PON1 also has been implicated in numerous human diseases in addition to vascular disease, such as Parkinson's disease (37)(38)(39)(40)(41), systemic lupus erythematosus (42)(43)(44), breast cancer ( 45,46 ), age-related macular degeneration (47)(48)(49), and diabetes ( 50 ), among other disorders ( 51 ). Given the recent failures of HDL-C to prevent atherosclerotic outcomes in recent trials and the varied effects of PON1 on numerous important human diseases, a fuller understanding of PON1 activity may shed light on the cardioprotective role of HDL.…”

Section: Description Of the Pon Gene Cluster Snvs In The Esp6500 Datamentioning

confidence: 99%

Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL

Kim

Burt

Crosslin

et al. 2013

Journal of Lipid Research

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“…20,21 The results are conflicting, and some reports suggest that both polymorphisms are positively associated with AMD and others demonstrate no association with AMD. 19,[22][23][24] In the current study, we have demonstrated that the L55M and Q192R polymorphisms were significantly associated with AMD. The 55MM and the 192QQ genotypes were less frequent in AMD patients than in the control subjects.…”

Section: Discussionmentioning

confidence: 78%