Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions

Hadjigeorgiou, Georgios M.; Malizos, Konstantinos N.; Dardiotis, Efthimios; Aggelakis, Konstantinos; Dardioti, Maria; Zibis, Aristeidis; Dimitroulias, Apostolos; Scarmeas, Nikolaos; Tsezou, Aspasia; Karantanas, Apostolos H.

doi:10.1002/jor.20393

Cited by 28 publications

(17 citation statements)

References 39 publications

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“…These risk genes/polymorphisms are involved in a series of biological processes, including the regulation of cholesterol (e.g., ApoE, CETP) (Nebes et al, 2001;Hogh et al, 2007;Godin et al, 2009;Paternoster et al, Brought to you by | Carleton University OCUL Authenticated Download Date | 6/18/15 3:37 AM 2009; Qureischie et al, 2009), the regulation of systemic blood pressure and cerebral blood flow (e.g., ACE, AGT, AGTR1, CYP11B, F3) (Amar et al, 1998;Schmidt et al, 2001;Verpillat et al, 2001;Hassan et al, 2002;Henskens et al, 2005;van Rijn et al, 2007;Smith et al, 2009;), the biosynthesis of DNA and RNA (e.g., MTHFR) (Kohara et al, 2003;Linnebank et al, 2009;Hong et al, 2009;Szolnoki et al, 2012), immune response and inflammation (e.g., IL-6, IL5RA, ITGB6, CAPN10, NR3C1, KITLG) (Fornage et al, 2008;van Rossum et al, 2008;Smith et al, 2009;Fernandez-Cadenas et al, 2011), neuron regeneration (e.g., BDNF) (Taylor et al, 2008), neuroinflammation (e.g., MMP2, MMP3, MMP9, MMP13) (Fornage et al, 2007;Smith et al, 2009;Fernandez-Cadenas et al, 2011), cystoskeleton and cell adhesion (e.g., KNS2, ADD1, A2M, ICAM1) (van Rijn et al, 2006;Szolnoki et al, 2007;Fernandez-Cadenas et al, 2011;Fornage et al, 2011), and oxidative stress (e.g., PON1, NOS3) (Schmidt et al, 2000a;Henskens et al, 2005;Hadjigeorgiou et al, 2007;Fernandez-Cadenas et al, 2011). Although these risk genes/polymorphisms were shown to be strongly associated with the increased risk of LA, th...…”

Section: Candidate Gene Association Studymentioning

confidence: 99%

Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology

Lin¹,

Huang

Tzeng

2015

Reviews in the Neurosciences

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AbstractLeukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically, LA is characterized by loss of myelin and axons, patchy demyelination, and denudation of ependyma in regions of WMH. Age and hypertension are the most importantly established risk factors for LA. However, the precise pathogenic mechanisms remain unclear. Together with the previous findings, our recent genetic results strongly supported that LA is associated with immune response and neuroinflammation. Therefore, we confidently hypothesized that LA was not only a common neuroimaging phenomenon in the elderly but also an emerging neuroinflammatory disorder in the central nervous system. This article focusing on neuroimaging classification, genetics basis, and putative molecular mechanism introduced the basic knowledge and current status of LA and put forward some of our research ideas and results from our molecular genetics research, which may pave the way for deciphering the putative pathogenic mechanism, risk factor, epigenetic index, and its application in diagnostic agents or drug target for prevention and treatment. Thus, it could provide clinicians and researchers with a specific and modern overview of LA to enable the understanding of recent progress and future directions in this illness.

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Section: Candidate Gene Association Studymentioning

confidence: 99%

Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology

Lin¹,

Huang

Tzeng

2015

Reviews in the Neurosciences

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“…The PON1-192QQ genotype was associated to increased risk for white matter lesions in Greek patients with osteonecrosis of the femoral head, while the PON1-55LM polymorphism was not associated with this pathology (Hadjigeorgiou et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase 1 Polymorphisms Are Not Related with the Risk for Multiple Sclerosis

et al. 2009

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It has been suggested a possible role of oxidative stress and lipid peroxidation in the inflammatory processes and in the pathogenesis of multiple sclerosis. Human serum paraoxonase 1 is a polymorphic enzyme encoded by the gene PON1, located in chromosome 7q21.3, that plays a major role in the metabolism of organophosporus compounds, and in the protection against oxidative stress. Paraoxonase-1 activity has been found decreased in the plasma of multiple sclerosis patients. An association between PON1 polymorphism and the risk of multiple sclerosis has been described in Italians. To investigate the possible association between the PON1 genotype and allelic variants of the polymorphisms L55M and Q192R and the risk for multiple sclerosis in the Spanish Caucasian population; we studied the frequency of the PON1 genotypes and allelic variants in 228 patients with multiple sclerosis and 220 healthy controls using a PCR-RLFP method. The frequencies of the PON1 genotypes and allelic variants did not differ significantly between patients and controls, and were unrelated with gender, age of onset, and course of the disease. The OR (95% confidence intervals) for the variant alleles PON1-55L and PON1-192R were 0.96 (0.73-1.26) and 1.01 (0.76-1.35), respectively. The results of the present study suggest that PON1 polymorphism is not related with the risk for multiple sclerosis in our population.

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“…Recent researches mainly focus on PON 192 and 55 polymorphisms, several trials found that they were associated with risk of ischemic vascular events as stroke and coronary heart disease [17]. One study also showed that PON-1 192QQ genotype increased risk for steroid-induced ONFH [18]. On the basis of these findings, we hypothesized that there might be a possible relationship between SNP of PON-1 and steroid-induced ONFH.…”

Section: Introductionmentioning

confidence: 94%

Association of a polymorphism in PON-1 gene with steroid-induced osteonecrosis of femoral head in Chinese Han population

et al. 2013

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BackgroundTreatment with steroids covers a wide spectrum of diseases in clinic. However, some users are suffering from serious side effects of steroid administration, while we enjoy the benefit it brings about. Osteonecrosis of the femoral head (ONFH) is a troublesome one among them. Recent studies have demonstrated that lipid metabolism disorder may play a vital role in pathogenesis of ONFH and mutation of the paraoxonase-1 (PON-1) gene may be involved in the occurrence of this disease. However, the relationship between polymorphisms of PON-1 and ONFH has not been thoroughly studied. The aim of this study was to determine whether PON-1 polymorphisms are associated with steroid-induced ONFH through a cohort study among Chinese Han population.MethodsThis trial applied a case–control scheme to compare the clinical data including PON-1 SNP among 94 patients and 106 control subjects to analyze the association between SNP and risk of steroid-induced ONFH. Time of Flight Mass Spectrometer is utilized for genotyping and the result was analyzed in multivariate analysis models.ResultsAccording to polymorphism test of rs662, its SNP was significantly associated with the risk of ONFH in overdominant analysis model [P value: 0.022; odds ratio (OR): 0.39]. However, genotype frequencies of rs662 of PON-1 gene between case and control group showed no differences (P > 0.05).ConclusionsOur data suggest for the first time that SNP (rs662) of the PON-1 gene was associated with the risk of steroid-induced ONFH. In addition, PAI-1 SNPs may play an important role in pathogenesis of ONFH.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/1501829501107336.

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Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions

Cited by 28 publications

References 39 publications

Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology

Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology

Paraoxonase 1 Polymorphisms Are Not Related with the Risk for Multiple Sclerosis

Association of a polymorphism in PON-1 gene with steroid-induced osteonecrosis of femoral head in Chinese Han population

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