A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women

Fortunato, Giuliana; Rubba, P.; Panico, Salvatore; Trono, D.; Tinto, Nadia; Mazzaccara, Cristina; Michele, Mario De; Iannuzzi, Arcangelo; Vitale, Dino Franco; Salvatore, Francesco; Sacchetti, Lucia

doi:10.1016/s0021-9150(02)00423-9

Cited by 49 publications

(36 citation statements)

References 34 publications

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“…In contrast to the cited studies, the 192Q allele was found in a higher frequency and was associated with the risk of cardiovascular system diseases in the German (125) and Polish (126) population. It was noted that the Q192R polymorphism of PON1 was not related to carotid intima thickness (127). A similar result was reported for Sicilian hypercholesterolemic patients in whom early carotid atherosclerosis and polymorphism were found unrelated (128).…”

Section: Effects On Cardiovascular Systemsupporting

confidence: 66%

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

Aydın¹,

Şahin²,

Aydın³

et al. 2012

Journal of Medical Biochemistry

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Summary: Although paraoxonase is synthesized in many tissues including the heart, colon, kidneys, lungs, small intestines and brain, its major locus of synthesis is the liver. PON1 is in close association with apolipoproteins and protects LDL against oxidation. It was reported that PON1 quantities dropped to 40 times lower than normal in cardiovascular diseases and diseases like diabetes, ulcerative colitis, Crohn's disease, chronic renal failure, SLE, Behcet's disease, cancer, hepatitis B, obesity, metabolic syndrome, Alzheimer's and dementia. It is speculated that the concerning decline in serum PON1 amount results from single nucleotide polymorphism in the coding (Q192R, L55M) and promoter (T-108C) sites of the PON1 gene. Additionally, circulating amounts of PON1 are affected by vitamins, antioxidants, fatty acids, dietary factors, drugs, age and lifestyle. This collection attempts to review and examine the past and present studies of paraoxonase and its relation with the cardiovascular system and some relevant diseases.Keywords: paraoxonase, polymorphism, cardiovascular system diseases Kratak sadr`aj: Iako se paraoksonaza sinteti{e u mnogim tkivima, uklju~uju}i srce, debelo crevo, bubrege, plu}a, tanko crevo i mozak, glavno mesto njene sinteze je jetra. PON1 je blisko povezana sa apolipoproteinima i {titi LDL od oksidacije. Koli~ine PON1 ~ak 40 puta ni`e od normalnog nivoa zabele`ene su u kardiovaskularnim bolestima i oboljenjima kao {to su dijabetes, ulcerozni kolitis, Kronova bolest, hroni~na bubre`na insuficijencija, sistemski eritemski lupus, Beh~etov sindrom, kancer, hepatitis B, gojaznost, metaboli~ki sindrom, Alchajmerova bolest i demencija. Spekuli{e se da pomenuti pad nivoa PON1 u serumu poti~e od polimorfizma pojedina~nih nukleotida na kodnim (Q192R, L55M) i promoterskim (T-108C) podru~jima gena PON1. Pored toga, na koli~inu PON1 u cirkulaciji uti~u vita mini, antioksidansi, masne kiseline, faktori ishra ne, le kovi, godine i na~in `ivota. Ovaj pregled predstavlja poku{aj da se izlo`e i razmotre pro{le i sada{nje studije o paraoksonazi i njenom odnosu sa kardiovaskularnim sistemom i nekim relevantnim bolestima.

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Section: Effects On Cardiovascular Systemsupporting

confidence: 66%

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

Aydın¹,

Şahin²,

Aydın³

et al. 2012

Journal of Medical Biochemistry

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“…Q192R, a common variant of the PON1 gene, is the major determinant of paraoxonase activity [60] . Several studies have shown that rare variants are associated with increased risk of ischemic stroke [61] and IMT [62] . However, several researchers [63] failed to replicate these data.…”

Section: Lipid Metabolismmentioning

confidence: 99%

Genetics of stroke

Guo

Liu

2010

Acta Pharmacol Sin

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Stroke is the second most common cause of death and the most common cause of disability in developed countries. Stroke is a multifactorial disease caused by a combination of environmental and genetic factors. Numerous epidemiologic studies have documented a significant genetic component in the occurrence of strokes. Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for stroke. Although a large group of candidate genes have been studied, most of the epidemiological results are conflicting. Studies of stroke as a monogenic disease have made huge progress, and animal models serve as an indispensable tool to dissect the complex genetics of stroke. In the present review, we provide insight into the role of in vivo stroke models for the study of stroke genetics.

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“…The LL genotype is less protective of LDL oxidation than the MM genotype [12], therefore an association between CHD risk and the LL genotype would be expected, and indeed an association has been demonstrated between PON55 LL and arterial atherosclerosis [37][38][39].…”

Section: Pon55 Polymorphism and Disease Riskmentioning

confidence: 99%

Paraoxonase activity and coronary heart disease risk in healthy middle-aged males: The PRIME study

et al. 2008

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Objective: Classic coronary heart disease (CHD) risk factors fail to explain the large gradient in CHD incidence between Northern Ireland and France. The Prospective Epidemiological Study of Myocardial Infarction (PRIME) study, a multicentre prospective study of 10,593 middle-aged males, investigated novel risk factors in these populations. We tested the hypotheses that (1) higher paraoxonase activity is associated with decreased CHD risk and (2) PON55 LL genotype is associated with increased CHD risk. Methods: Paraoxonase activity was measured in 299 men who had developed CHD at 5-year follow-up and in 576 matched controls. DNA was available from 247 cases and 433 controls for genotyping for the PON55 polymorphism. Results: There was no significant difference in paraoxonase activity between cases and controls (geometric means 73.8 and 74.2 U/l; p = 0.81). There was no significant difference in CHD risk between fifths of paraoxonase activity either before (p = 0.55) or after adjustment for classical risk factors (p = 0.58).There was no significant association between genotype and CHD risk; relative to the LL genotype, the OR (95% CI) for the LM and MM genotypes were 0.92 (0.66-1.29) and 0.83 (0.50-1.36), respectively. The frequency of the L allele in cases (66.6%) and controls (64.5%) did not differ significantly, p = 0.45. Conclusions: These findings suggest that neither paraoxonase activity nor PON55 genotype is associated with CHD risk in males in the PRIME study.

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A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women

Cited by 49 publications

References 34 publications

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

The Past and Present of Paraoxonase Enzyme: Its Role in the Cardiovascular System and Some Diseases

Genetics of stroke

Paraoxonase activity and coronary heart disease risk in healthy middle-aged males: The PRIME study

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