Association of Paraoxonase 1 L55m and Q192r Single-Nucleotide Polymorphisms With Age-Related Macular Degeneration

Söğüt, Erkan; Ortak, Hüseyin; Aydoğan, Leyla; Benli, İsmail

doi:10.1097/iae.0b013e318287da59

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…In our study, we did not observe that patients with exudative AMD show decreased arylesterase activity of apoB depleted sera. Polymorphisms in the PON-1 gene are associated with AMD [ 30 – 32 ].…”

Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration

Pertl¹,

Kern²,

Weger³

et al. 2016

PLoS ONE

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PurposeHigh-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients.MethodsBlood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants.ResultsIn our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01).ConclusionsThe investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration

Pertl¹,

Kern²,

Weger³

et al. 2016

PLoS ONE

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“…Both enzymes are capable to restrain LDL oxidation 34 and trigger antioxidant properties along with cholesterol efflux of HDL [35], [36]. Association of PON2 and PON3 polymorphism with various disorders has sparingly been studied [14], [15], [16], [17], [18], [19], [20], [21]. Present study was conducted to explore association between senile cataract and PON2 and PON3 polymorphism.…”

Section: Discussionmentioning

confidence: 99%

“…Paraoxonases are calcium dependent antioxidant enzymes constituting three isoforms PON1, PON2 and PON3 10 . PON1 polymorphism has been studied in different disorders including cataract,[11], [12] diabetes, 13 age related macular degeneration, 14 Alzheimer’s disease, 15 Behcet’s disease, 16 and atherosclerosis 17 . Data for PON2 and PON3, however, is limited.…”

Section: Introductionmentioning

confidence: 99%

Association of PON2 and PON3 polymorphism with risk of developing cataract

Baig

Ata-ur-Rehman

Zarina

2019

Saudi Journal of Ophthalmology

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Purpose Paraoxonases (PON) are calcium bound enzymes offering protection against oxidative stress by working as endogenous free-radical scavenging molecules. Oxidative stress has been implicated in pathophysiology of many diseases including cataract. Lens opacity is an age related disorder which is a principal cause of blindness in Pakistani population. Relationship of PON2 and PON3 polymorphism with genetic predisposition for incidence of cataract has not been investigated till date. Objective of the current study was to explore possible association between PON2 and PON3 polymorphism with incidence of cataract in local population. Methods Our study design comprised of fifty-one cataractous and fifty-nine healthy individuals. Identification of single nucleotide polymorphism (SNP) at positions (C311S and G148A) for PON2 and C133A for PON3 was conducted using restriction fragment length polymorphism (RFLP). Results Statistical analysis revealed significant association of PON2 G148 allele with incidence of cataract. GG allele was found to be higher in cataract patients as compared to control ( p < 0.001) suggesting distribution of PON2 G148A genotype and allele frequency is linked with cataractogenesis. There was no noticeable association between PON2 C311S and PON3 C133A. Significant difference was observed in distribution of 311CS/148A combined genotype with highest frequency in control individuals (88.89%), while 311S/148G combined genotypes showed the highest frequencies among the cataract patients (71.42%). Conclusion Our data suggests mutation at G148A might be related with incidence of cataract in studied population.

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