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NADPH Oxidase Gene Polymorphism is Associated with Mortality and Cardiovascular Events in 7-Year Follow-Up.

ABSTRACT: The CYBA gene encodes the regulatory subunit of NADPH oxidase, which maintains the redox state within cells and in the blood vessels. That led us to investigate the course of coronary artery disease (CAD) with regards to CYBA polymorphisms. Thus, we recruited 1197 subjects with coronary atherosclerosis and observed them during 7-year follow-up. Three CYBA polymorphisms: c.214C>T (rs4673), c.-932G>A (rs9932581), and c.*24G>A (1049255) were studied for an association with death, major adverse cardiovascular events (MACE) and an elective percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG). We found an association between the CYBA c.214C>T polymorphism and two end points: death and PCI/CABG. CYBA c.214TT genotype was associated with a lower risk of death than C allele (9.5% vs. 21%, p < 0.05) and a higher risk of PCI/CABG than C allele (69.3% vs. 51.7%, p < 0.01). This suggests that the CYBA c.214TT genotype may be a protective factor against death OR = 0.47 (95%CI 0.28-0.82; p < 0.01), while also being a risk factor for an elective PCI/CABG OR = 2.36 (95%CI 1.15-4.82; p < 0.05). Thus, we hypothesize that among patients with coronary atherosclerosis, the CYBA c.214TT genotype contributes to atherosclerotic plaque stability by altering the course of CAD towards chronic coronary syndrome, thereby lowering the incidence of fatal CAD-related events.

SUBMITTER: Racis M

PROVIDER: S-EPMC7290726 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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NADPH Oxidase Gene Polymorphism is Associated with Mortality and Cardiovascular Events in 7-Year Follow-Up.

Racis Milena M Sobiczewski Wojciech W Stanisławska-Sachadyn Anna A Wirtwein Marcin M Bluj Elżbieta E Nedoszytko Michał M Borzyszkowska Joanna J Limon Janusz J Rynkiewicz Andrzej A Gruchała Marcin M

Journal of clinical medicine 20200514 5

The CYBA gene encodes the regulatory subunit of NADPH oxidase, which maintains the redox state within cells and in the blood vessels. That led us to investigate the course of coronary artery disease (CAD) with regards to CYBA polymorphisms. Thus, we recruited 1197 subjects with coronary atherosclerosis and observed them during 7-year follow-up. Three CYBA polymorphisms: c.214C>T (rs4673), c.-932G>A (rs9932581), and c.*24G>A (1049255) were studied for an association with deat ...[more]

PMID: 32423015

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Project description:BackgroundAdvanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up.MethodsDuring year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016.ResultsThe participants were mainly men (59.5%), 51.5 ± 16.7 years old, with BMI 25.0 ± 4.1 kg/m2, diabetes duration 21.5 ± 13.6 years, HbA1C 7.6 ± 1.1%. LDL cholesterol was 1.04 ± 0.29 g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3 ± 26.6 ml/min/1.73 m2. Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (≥ 30 mg/24 h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63 ± 0.73 arbitrary units (AU) vs 2.08 ± 0.54 for other patients (p = 0.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HR = 4.13 [1.30-13.07]; p = 0.02 for 1 AU of SAF) and Kaplan-Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (p = 0.001).ConclusionA high SAF predicts MACE in patients with T1D.

Dataset Information

NADPH Oxidase Gene Polymorphism is Associated with Mortality and Cardiovascular Events in 7-Year Follow-Up.

Publications

NADPH Oxidase Gene Polymorphism is Associated with Mortality and Cardiovascular Events in 7-Year Follow-Up.

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