PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population

Arca, Marcello; Ombres, Domenico; Mestice, Anna; Campagna, F.; Madon, E; Tanzilli, Gaetano; Campa, Pietro Paolo; Ricci, Giorgio; Verna, Roberto; Pannitteri, Gaetano

doi:10.1046/j.1365-2362.2002.00935.x

Cited by 58 publications

(35 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(39) In addition, Blatter-Garin et al reported that homozygosity for the 55Leu allele of PON1 is an independent risk factor for CHD in non-insulin-dependent diabetics (44), which is supported by other studies (74, 128). In contrast, some studies conducted in patient groups of different ethnicities found no significant association between the 55 polymorphism and the presence of CHD (15,214,291,358).…”

Section: Pons Polymorphisms and Coronary Artery Diseasementioning

confidence: 81%

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

She

Chen

Yan

et al. 2012

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar b propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence. Clinical observations focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Many other conditions, such as diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The abundance and/or activity of PONs can be regulated by lipoproteins and their metabolites, biological macromolecules, pharmacological treatments, dietary factors, and lifestyle. In conclusion, both previous results and ongoing studies provide evidence, making the PON cluster a prospective target for the treatment of atherosclerosis. Antioxid. Redox Signal. 16, 597-632.

show abstract

Section: Pons Polymorphisms and Coronary Artery Diseasementioning

confidence: 81%

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

She

Chen

Yan

et al. 2012

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…The PON1 55 Leu and 192 Arg isoforms have been associated to an increased risk of CAD in some clinical studies [20-35], but not all [36][37][38][39][40][41][42][43][44][45][46][47][48][49]. This controversy was addressed by a recent metaanalysis including about 24 000 subjects [50], which showed no significant association between Leu55Met and CAD.…”

Section: Discussionmentioning

confidence: 99%

“…The HDL particles from 55 Met/Met and 192 Gln/Gln individuals have been demonstrated to be most effective in protecting LDL from oxidative modification [19]. The alleles less effective in protecting from oxidative stress, 55 Leu and the 192 Arg, have been associated with an increased risk of vascular disease in some clinical studies [20- 35], but not all [36][37][38][39][40][41][42][43][44][45][46][47][48][49]. A recent meta-analysis showed no significant association between 55 Leu allele and coronary heart disease, whereas a weak, but statistically significant increased risk (OR=1.12 with 95% CI=1.07-1.16) was found for the 192 Arg allele [50].…”

Section: Introductionmentioning

confidence: 99%

Interaction between metabolic syndrome and PON1 polymorphisms as a determinant of the risk of coronary artery disease

et al. 2005

View full text Add to dashboard Cite

The enzyme serum paraoxonase plays an important role in antioxidant defences and prevention of atherosclerosis. Metabolic syndrome (MS) is a clinical condition associated with increased oxidant stress and cardiovascular mortality. Two common polymorphisms of serum paraoxonase, PON1 Leu(55)Met and Gln(192)Arg, have been postulated to modulate the cardiovascular risk. We studied 915 subjects with angiographic documentation: 642 subjects with coronary atherosclerosis and 273 with normal coronary arteries. Two hundred and twenty-four subjects met the diagnostic criteria of MS. We found a significant interaction between MS and both the PON1 polymorphisms in determining the risk of coronary artery disease (P<0.05 by likelihood-ratio test). The 55Leu and the 192Arg alleles, associated with reduced protection against lipid peroxidation, were associated with coronary artery disease only in the MS subgroup. Subjects with MS and both 55Leu and 192Arg alleles had significantly increased risk (OR=9.38 with 95% CI=3.02-29.13 after adjustment by multiple logistic regression) as compared to subjects without MS and with 55Met/Met-192Gln/Gln genotype. No increased risk was found for subjects with MS and the 55Met/Met-192Gln/Gln genotype. This study highlights a potential example of genetic (paraoxonase polymorphisms)-clinical (MS) interaction influencing cardiovascular risk.

show abstract

“…Few case-control studies of the 55 polymorphism have been done. Some have shown an association between the PON1 55L allele and atherosclerosis 83,93 , but others have not 84,94 . However, no prospective studies of CAD and PON1 polymorphisms are available.…”

Section: Pon1 Coding Region Polymorphisms and Cadmentioning

confidence: 99%

Paraoxonase 1 (PON1) Activity, Polymorphisms and Coronary Artery Disease

Gupta¹,

Gill²,

Singh³

2012

Coronary Artery Disease - New Insights and Novel Approaches

View full text Add to dashboard Cite

PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population

Cited by 58 publications

References 36 publications

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

Interaction between metabolic syndrome and PON1 polymorphisms as a determinant of the risk of coronary artery disease

Paraoxonase 1 (PON1) Activity, Polymorphisms and Coronary Artery Disease

Contact Info

Product

Resources

About