The Arg allele in position 192 of PON1 is associated with carotid atherosclerosis in subjects with elevated HDLs

Gnasso, Agostino; Motti, Corradino; Irace, Concetta; Gennaro, I. Di; Pujia, Arturo; Leto, Elio; Ciamei, Monica; Crivaro, Andrea; Bernardini, Sergio; Federici, Giorgio; Cortese, Claudio

doi:10.1016/s0021-9150(02)00070-9

Cited by 33 publications

(22 citation statements)

References 26 publications

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“…Several studies have examined PON1 gene variants with respect to IMT, with some showing an association [11, 14, 16, 17, 29], and others failing to find an effect of different alleles on IMT [10, 12, 13, 15, 30, 31]. Because of the conflicting results the role of the PON1 gene in carotid artery disease is currently unclear.…”

Section: Discussionmentioning

confidence: 99%

Association between Human Paraoxonase 1 Activity and Intima-Media Thickness in Subjects under 55 Years of Age with Carotid Artery Disease

et al. 2007

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Background: Human serum paraoxonase (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (oxLDL); therefore, it may protect against atherosclerosis. PON1 activity and polymorphisms have been inconsistently associated with carotid artery disease. The goal of this study was to clarify the role of PON1 activity and phenotype on carotid artery disease and its correlation with some inflammatory and immune markers in subjects under 55 years with early-onset carotid atherosclerosis. Methods: Sixty patients with occlusive carotid artery disease and 30 healthy controls were enrolled. Intima-media thickness (IMT) was measured by high-resolution ultrasound of both common carotid arteries. Anti-oxLDL antibody levels were determined by ELISA. Results: In the whole study population we found a negative correlation between PON1 activity and IMT (r = –0.27, p = 0.011), and between salt-stimulated PON1 activity and IMT (r = –0.24, p = 0.02). Both PON1 activity and salt-stimulated PON1 activity negatively correlated with anti-oxLDL levels (r = –0.28, p = 0.008; r = –0.26, p = 0.01). PON1 activity was lower in patients compared to controls; however, the difference was not significant.PON1 phenotype distribution of patients and controls did not differ significantly. Conclusion: The importance of PON1 activity as a predictive risk factor for early-onset occlusive carotid artery disease should be assessed in future studies.

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Section: Discussionmentioning

confidence: 99%

Association between Human Paraoxonase 1 Activity and Intima-Media Thickness in Subjects under 55 Years of Age with Carotid Artery Disease

et al. 2007

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“…Association between PON1 polymorphisms and atherosclerosis is controversial. The M55L and Q192R polymorphisms in PON1 gene were shown to be associated with CAD (Imai et al 2000) and increased carotid atherosclerosis (Fortunato et al 2003;Gnasso et al 2002). The C107T and the Q192R polymorphisms in PON1 gene were associated with risk of stroke in some studies Ranade et al 2005).…”

Section: High-density Lipoprotein Cholesterol Metabolismmentioning

confidence: 98%

Molecular genetics of atherosclerosis

2009

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Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic polymorphisms significantly influence susceptibility to atherosclerotic vascular diseases. A large number of candidate genes, genetic polymorphisms and susceptibility loci associated with atherosclerotic diseases have been identified in recent years and their number is rapidly increasing. In this review we focus on some of the major candidate genes and genetic polymorphisms associated with human atherosclerotic vascular diseases.

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“…123 An eleventh study showed higher IMT in RR homozygotes than Q allele carriers; 124 the twelfth showed plaque to be more frequent in PON 1 192R carriers with high levels of high-density lipoprotein, but no difference in plaque by genotype in subjects with low levels of high-density lipoprotein. 125 The thirteenth showed the R allele to be more frequent in older persons with moderate versus no atherosclerosis. 62 Association studies of the PON 1 55 polymorphism have suggested that IMT and plaque are increased in L allele carriers, but relationships are complex.…”

Section: Paraoxonasementioning

confidence: 99%

Genetics of Ultrasonographic Carotid Atherosclerosis

Boerwinkle

O’Donnell

Wilson

2004

ATVB

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Abstract-The search for genes related to the cause of common complex disorders such as cardiovascular disease has been frustrating, partly because of the many factors known to contribute to cardiovascular disease and the potential "distance" of cardiovascular disease as a phenotype from genes and gene products. Linkage and association studies for phenotypes more proximal in the pathway from DNA sequence variation to overt clinical disease, such as ultrasound-defined carotid atherosclerosis, may potentially be more enlightening. Only one genetic variant previously reported to be associated with atherosclerosis or clinically evident cardiovascular disease, matrix metalloproteinase (MMP) 3, has shown consistently positive associations with carotid disease, although it has not been studied widely. Another, PON1 L55M, is weakly associated in subgroups only, and 2, ApoE and MTHFR, are equivocal. Genetic variants reported to be associated with clinical cardiovascular disease show weak or no relationship to carotid atherosclerosis. This may reflect the known inconsistency in associations of genetic variants with clinical cardiovascular disease itself. Alternatively, genetic determinants of ultrasound-defined carotid atherosclerosis may differ from those of clinically manifest cardiovascular disease and may require pursuit through large-scale genomic studies of carotid atherosclerosis as a distinct phenotype. Key Words: atherosclerosis Ⅲ genes Ⅲ human Ⅲ carotid artery Ⅲ cardiovascular disease I dentification of genes influencing complex clinically manifest traits such as myocardial infarction and stroke has been difficult, in part because of the many interacting factors known to contribute to these traits and the large conceptual, physiological, and temporal distance between gene variation and clinical manifestation of adult disease. 1,2 In addition, genetic analysis of a disease end point is complicated by vagaries in disease diagnosis, including variations in presentation, access to care, and acumen of care providers. Studies of phenotypes further upstream in the pathway from DNA sequence variation to overt clinical disease, such as ultrasonographic carotid atherosclerosis, may thus yield valuable information not obtainable by studying clinical conditions alone.Intimal-medial thickening (IMT) of the carotid artery determined by B-mode ultrasonography is a quantitative measure of atherosclerosis that has a graded, predictive relationship to overt clinical disease. 3 Carotid IMT can be measured noninvasively in population-based samples free of many of the biases of clinically identified cases and controls. [3][4][5] Focal carotid wall thickening (plaque) and lumen narrowing (stenosis) can also be imaged and also predict cardiovascular events. 6 Ultrasonographic measures of the carotid artery may thus provide a useful intermediate phenotype for the identification of atherosclerosis-related genes. In this review, we describe the most commonly reported ultrasound-defined carotid phenotypes and estimates of their heritabilit...

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The Arg allele in position 192 of PON1 is associated with carotid atherosclerosis in subjects with elevated HDLs

Cited by 33 publications

References 26 publications

Association between Human Paraoxonase 1 Activity and Intima-Media Thickness in Subjects under 55 Years of Age with Carotid Artery Disease

Association between Human Paraoxonase 1 Activity and Intima-Media Thickness in Subjects under 55 Years of Age with Carotid Artery Disease

Molecular genetics of atherosclerosis

Genetics of Ultrasonographic Carotid Atherosclerosis

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