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

Elgwad, Eman R. Abd; Behiry, Eman G.; Swailem, fathy M.; Ameen, Seham Gouda; Abdelhasib, Dalia M.; Elhamid, Rabab O. Abd

doi:10.1016/j.amsu.2018.05.007

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…64 The importance of this PON1 coding polymorphism has also been demonstrated in findings by Abd Elgwad and coworkers, which estimated the response of the HDLcholesterol concentration to statin therapy. 65 They found that Q allele carriers responded better to statin therapy with respect to increased HDL-cholesterol concentration, than RR homozygotes. This opens a new area of potential drug design studies related to statin therapy clinical usefulness.…”

Section: Pon1 and Vascular Diseasesmentioning

confidence: 99%

Paraoxonase 1 and atherosclerosis‐related diseases

et al. 2019

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A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high‐density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti‐inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis‐related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end‐stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.

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Section: Pon1 and Vascular Diseasesmentioning

confidence: 99%

Paraoxonase 1 and atherosclerosis‐related diseases

et al. 2019

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“…Many studies evaluating how different statins influence PON1 activity are provided [32,33,34], a recently published meta-analysis [35] confirms, independent of particular drug, dose, treatment duration and serum lipid profile, an effect of enhancing PON1 activities and concentration. Additionally, it is described that individual response to treatment with statins is dependent on PON1 Q192R polymorphism [36], which may explain the significant difference of PON1 paraoxonase activity between patients with and without treatment noted in our study.…”

Section: Discussionmentioning

confidence: 66%

Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery

Wysocka

Cybulski

Wysokiński

et al. 2019

JCM

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Background: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. Materials and methods: Investigated population consisted of 71 patients aged 43–76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for –108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR–RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. Results: Significant correlations between diabetes mellitus and paraoxonase activity (R = –0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = –0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. Conclusions: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.

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“…[22] One prospective and one crosssectional studies for patients with Q allele of the PON1 Q192R polymorphism HDL-C goals were attained moreover than patients with RR homozygosity. [23,24] In Japanese, diabetic patient with Q allele who was treated with…”

Section: Pon1 Genementioning

confidence: 99%

“…Ciuculete et al (2017) [19] Prospective Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. Elgwad et al (2018) [23] Prospective Q192R polymorphism of PON1gene had important role in interindividual variety in accomplishment of HDL-C goals in response to statins. Sumi et al (2017) [24] Cross-sectional PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism.…”

Section: Article Title Study Design Conclusionmentioning

confidence: 99%

“…The literature search was limited by available databases and access. The number of publications in this topic is relatively [9,[13][14][15] X X SLCO1B1 [16,17] X X APOE [9,10,14,18,19] X X PON1 [23,24] X X RYR2 [27] X X RYR2 [17] X X TLR4, [10] LTa C804A, [31] LPA, [9] NPC1L1, [18] HLA-G, [32] CYP3A4*2, [33] eNOS, [33] CYP2D6, [34] ABCB1, [35] CETP, [14] SREBF1,2, [36] KIF16, [37] HMGCR, [14,19] SORT1/CELSR2/PSRC1 [19,24] X X ACE, [10] HL, [10] WDR52, [38] CDH13, [39] CYP3A4*2 [40] X X HLA-DRB1, [17] LILRB5 [25] X X COQ2, [15] GATM [17,30] X X Pharmacogentics of statins Anas S. Aldawsari and Mohammad S. Shawaqfeh scares which made the literature search a real challenge. There were limited numbers of randomised controlled studies and meta-analysis in the topic.…”

Section: Limitationsmentioning

confidence: 99%

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Clinical evidence of pharmacogenetics of statins: systematic literature review

Aldawsari

Shawaqfeh

2019

J Pharm Health Serv Res

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Objectives A systematic review was conducted to explore the clinical evidence of pharmacogenetic testing with statins in a personalised approach to minimise the incidence of adverse drug reaction (ADR), ensure better response and optimise medication adherence. Methods Systematic literature review using PubMed and EMBASE/Medline database that includes all clinically relevant pharmacogenomic studies involving statins. Key findings Twenty-four articles were evaluated for a total of 120 articles screened. The included studies were classified according to study design (two randomised controlled trial studies (RCTs), three meta-analysis studies, two interventional studies, four prospective studies, 10 case-control studies, two cross-sectional studies and one data analysis study). There were 23 different genetic polymorphisms related to statins were studied clinically with the specified outcome either LDL-lowering response or adverse drug reaction. Those genes were diverse and involve metabolic enzymes, transporters and other receptors. Conclusions Many studies suggest a strong association between clinical outcomes and certain genes relevant to statins. However, these studies were observational and only a few were randomised controlled trials (RCTs). The strength of evidence to support pharmacogenetic testing for statin is not adequate.

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

Cited by 6 publications

References 25 publications

Paraoxonase 1 and atherosclerosis‐related diseases

Paraoxonase 1 and atherosclerosis‐related diseases

Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery

Clinical evidence of pharmacogenetics of statins: systematic literature review

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