Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus

Yığıt, Serbülent; Uzun, Suheyla; Rustemoglu, Husniye; Dashatan, Payam Amiri; Soylu, Hüseyin; Atmaca, Ayşegül; Rüstemoğlu, Aydın; Kuruca, Nilüfer; Karakuş, Nevin

doi:10.2174/1567202617999201214230147

Cited by 7 publications

(4 citation statements)

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“…This is in addition to drugs. 9 In these patients, the pharmacodynamics of clopidogrel was enhanced by the intensity of smoking, and smokers who received clopidogrel had low platelets reactivity. 10 In this study, we investigated whether smoking enhances clopidogrel responsiveness in patients with ischemic heart disease (IHD) following PCI.…”

Section: Introductionmentioning

confidence: 99%

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The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Aldallal,

Mohammad,

Rgeeb

et al. 2023

F1000Res

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Background: Previous studies have pointed out the disproportionate action of clopidogrel in inhibiting platelet aggregation due to smoking more than ten cigarettes per a day. This study was designed to examine whether smoking enhances clopidogrel responsiveness in patients who are clinically diagnosed with coronary artery disease (CAD), following percutaneous coronary intervention (PCI). Methods: A total of 324 IHD participants were enrolled in a case-control study. Platelet function test was performed to all participants two hours before PCI procedure to measure clopidogrel response. Participants were then categorized into a non-responder group (case group n = 111) and responder group (control group n = 213). Each group was subdivided into a smoker group and a non-smoker group. All participants received clopidogrel loading dose equivalent to 600 mg and scheduled for elective PCI. Participants’ age, gender, family history of chronic illnesses was recorded in this study. Results: Smoking participants displayed a significant higher level of hemoglobin as compared to the non-smoking participants among the responder and the non-responder study groups (14.6±0.55 vs. 13.12±0.38, P < 0.029; 14.3±0.31 versus 12.96±0.39, P < 0.033) but lower AUC level (17±9 vs. 45±6, P < 0.005; 62±3 vs. 95±7, P < 0.008). Additionally, smoking intensity enhanced clopidogrel responsiveness by odd’s ratio 0.4213 at 95% C.I. (0.259 - 0.684), P < 0.0002. Conclusions: Current smokers had a good response to clopidogrel therapy which exerted a beneficial effect when undergoing PCI as compared to non-smokers. The marked difference in AUC between smokers and non-smokers could be related to the variance in hemoglobin level. The smokers’ paradox needs further justification to confirm this concept.

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Section: Introductionmentioning

confidence: 99%

“…Clopidogrel, which is P2Y 12 inhibitors was the first medication in this category, play an essential role in antiplatelet therapy and consequently in the treatment and prevention of CVD. 1,9 However, there are several factors which may alter personal response to clopidogrel therapy. This is in addition to drugs.…”

Section: Introductionmentioning

confidence: 99%

The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Aldallal,

Mohammad,

Rgeeb

et al. 2023

F1000Res

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“…This is in addition to drugs. 10 The main objective of the following project is to measure the efficacy of 2 known doses of atorvastatin (daily intake of 20 mg, and 40 mg oral supplementation for 16 weeks) on serum nitric oxide level and lipid profile in patients with heart disease, with and without clopidogrel resistance.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance

et al. 2023

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Introduction and aim: Lipid lower drugs have been widely used to prevent atherosclerosis in patients with heart disease. This study aims to compare the findings between the efficacy of 20 mg/day and 40 mg/day atorvastatin supplementation for 16 weeks, on nitric oxide level and lipid profile in clopidogrel resistant and non-resistant patients with coronary heart disease (CAD). Methods: This retrospective study included two hundred and eighty-four participants with CAD. Patients were subjected to platelets function to determine the clopidogrel resistance. 88 patients were included into the clopidogrel resistant group, and 196 patients were included into the clopidogrel non-resistant group. Each group was subdivided into two subgroups depending on the daily dose of atorvastatin therapy (daily intake of 20 mg and 40 mg, orally). Results: Irrelevant to the study group, there was significant increase in serum levels of NO following 40 mg/day clopidogrel supplementation for 16 weeks as compared to 20 mg/day clopidogrel supplementation, P ≤ 0.05. This was associated with a significant reduction in serum lipids (total cholesterol and LDL-C), P ≤ 0.05. Conclusion: Atorvastatin supplementation improves serum nitric oxide level, and serum lipid profile in patients with CAD with and without clopidogrel resistance.

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“…The clinical implications of the single nucleotide polymorphisms rs2070744 (−786T>C in the promoter region) and rs1799983 (894G>T, Glu298Asp) and the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR -rs61722009) of the endothelial nitric oxide synthase (eNOS) in several health problems have been studied (i.e., cardiovascular diseases and diabetes mellitus) [1][2][3]. These variants are located in an important region of the NOS3 gene and they possibly affect the production of nitric oxide (NO) and physiological processes [4].…”

Section: Introductionmentioning

confidence: 99%

VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study

Forgerini

Urbano

Nadai

et al. 2022

JGLD

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Background and Aims: Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR - rs61722009) of the endothelial nitric oxide synthase (eNOS) on the drug response, we assessed the influence of this polymorphism for the risk of upper gastrointestinal bleeding (UGIB). Methods: A case-control study, including 200 cases and 706 controls, was conducted in a Brazilian hospital complex. Cases were participants with UGIB diagnosis. Controls were participants admitted to surgical procedures not related to gastrointestinal problems. The 4b/4a VNTR was determined through polymerase chain reaction followed by fragment analysis. Conditional logistic regression models were designed. The additive interaction between the presence of the 4b/4a VNTR variant and the use of low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) was calculated by fitting the Cox regression model through the parameters of Synergism index (S) and Relative Excess Risk Due To Interaction (RERI). Results: The presence of the 4b/4a VNTR variant did not increase the risk of UGIB: carriers of the 4a/4a genotype (OR=0.37, 95%CI: 0.09-1.45) and of the variant allele “4a” (OR=0.91, 95%CI: 0.55-1.51). The risk of UGIB in LDA users carriers of the wild genotype (OR=4.96, 95%CI: 2.04- 2.06) and the variant allele “4a” (OR=3.49, 95%CI: 1.18-10.38) is similar, as well as for NSAID users carriers of the wild genotype (OR=5.73, 95%CI: 2.61-12.60) and variant allele “4a” (OR=5.51, 95%CI: 1.42-15.82). No additive interaction was identified between the presence of the genetic variant and the use of LDA [RERI: -1.44 (95%CI: -6.02–3.14; S: 0.63 (95%CI: -1.97–1.15)] and NSAIDs [RERI: -0.13 (95%CI: -6.79–6.53; S: 0.97 (95%CI: -0.23–4.19)] on the UGIB risk. Conclusion: Our data suggests that there is no increase in the magnitude of UGIB risk in LDA and NSAIDs users’ carrying the variant allele “4a”.

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Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus

Cited by 7 publications

References 0 publications

The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance

VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study

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