Dataset Information

Association between Q192R polymorphism in the PON1 gene and statin responses in cardiac patients.

ABSTRACT:

Introduction

Paraoxonases are a group of different forms enzymes that consist of three non-similar isoforms, PON1, PON2 and PON3, which are located near to each other on the long arm of chromosome7. This study aims to investigate the association of a Q192R polymorphism of PON1 gene and statin response in patients with ischemic heart disease with dyslipidemia.

Methods

The studied population included three hundred patients with coronary artery disease with dyslipidemia who were prescribed statins. Total lipid profile was measured in these patients both before and after approximately 6 months of treatment. Q192R polymorphism of PON1 gene was assessed by real-time PCR.

Results

There were no significant differences in baseline lipid levels according to different genotypes in all studied casesof Q192R (rs662) polymorphism. HDL-C goals were attained less often in patients with RR homozygosity than in Q allele carriers. Analysis by univariate logistic regression confirmed that QQ/QR carriers had an increased chance of attaining HDL-C goals.

Conclusion

This study shows that the Q192R polymorphism of PON1gene has important role in interindividual variety in accomplishment of HDL-C goals in response to statins.

SUBMITTER: Abd Elgwad ER

PROVIDER: S-EPMC6004736 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Association between Q192R polymorphism in the PON1 gene and statin responses in cardiac patients.

Abd Elgwad Eman R ER Behiry Eman G EG Swailem Fathy M FM Ameen Seham G SG Abdelhasib Dalia M DM Abd Elhamid Rabab O RO

Annals of medicine and surgery (2012) 20180512

<h4>Introduction</h4>Paraoxonases are a group of different forms enzymes that consist of three non-similar isoforms, <i>PON1, PON2 and PON3</i>, which are located near to each other on the long arm of chromosome7. This study aims to investigate the association of a Q192R polymorphism of PON1 gene and statin response in patients with ischemic heart disease with dyslipidemia.<h4>Methods</h4>The studied population included three hundred patients with coronary artery disease with dyslipidemia who we ...[more]

PMID: 29922459

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Project description:BackgroundLow levels of antioxidant paraoxonase 1 (PON1) enzyme activity, PON1-Q192R polymorphism (a glutamine (Q) to arginine (R) substitution at position 192), PON1-L55M polymorphism (a leucine (L) to methionine (M) substitution at position 55), and oxidized low-density lipoprotein (oxLDL) are risk factors for coronary heart disease. Aerobic exercise improves PON1 activity, but the effects of hypoxic exercise are yet unclear. The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms.MethodsSerum PON1 and arylesterase activities (ARE), PON1, PON3, and oxLDL protein levels (by using the enzyme-linked immunosorbent assays) were determined in an athletic group (42 trained male underwater rugby players; age = 21.7 ± 4.2 years, mean ± SD) and a control group (43 sedentary men; age = 23.9 ± 3.2 years). The polymorphisms were determined from genomic DNA samples.ResultsPON1 activity (25.1%, p = 0.052), PON3 (p < 0.001), and oxLDL (p < 0.001) of the athletic group, including most genotype groups, were higher than those of the control group. In comparison to the controls, PON1 activity levels (p = 0.005) of the PON1-Q192R homozygote QQ genotype group and PON1 activity levels (30%, p = 0.116) of the PON1-L55M homozygote LL genotype group were higher, whereas ARE activity values of athletic R allele carrier (Rc = QR + RR) (p = 0.005) and LL group (p = 0.002) were lower than the control genotype groups related to their polymorphisms.ConclusionHypoxic training can cause (1) significant oxidative stress, including oxLDL, and an antioxidant response (increase in PON1 activity and PON3), (2) differences in the activity of PON1 and ARE, which are modified by PON1-Q192R and PON1-L55M polymorphisms, respectively, and (3) improvements in PON1 activity of QQ and LL groups. However, hypoxic training can cause a disadvantage of LL and Rc groups for ARE.

Project description:Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association. Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle-Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27-3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43-3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41-10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47-5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64-5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38-6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74-2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57-3.12, P = 0.52). The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.

Dataset Information

Association between Q192R polymorphism in the PON1 gene and statin responses in cardiac patients.

Introduction

Methods

Results

Conclusion

Publications

Association between Q192R polymorphism in the PON1 gene and statin responses in cardiac patients.

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