Polymorphisms in CD36 and STAT3 Genes and Different Dietary Interventions Among Patients With Coronary Artery Disease (GENUTRI)

Effect of Polymorphisms in CD36 and STAT3 Genes on Different Dietary Interventions Among Patients With Coronary Artery Disease: a Randomized Clinical Trial With a Nutrigenetic Approach

Background: Cardiovascular diseases are the major health problem worldwide and the understanding of genetic contributions on the development of cardiovascular diseases is increasing significantly. The CD36 is a protein associated with uptake of oxidized forms of LDL and the single nucleotide polymorphism (SNP) rs1761667 A/G in the CD36 gene is correlated with increased consumption of total fat. The transcription factor STAT3 is released during the inflammatory acute phase response and the SNP rs8069645 G/A in the STAT3 gene is associated with abdominal obesity and higher intake of saturated fat. Studies have been shown the benefits of the Mediterranean diet in secondary prevention of cardiovascular disease and these dietary patterns have been often studied with nutrigenetic approach; these studies, however, are often limited to European populations, making it difficult to generalize to different populations.

Hypothesis: Different dietary approaches may similarly influence in modifying metabolic, inflammatory and anthropometric profile, especially among patients with coronary arterial disease (CAD). The genetic interaction with environmental factors such as the nutrient intake, and the prescription of a different diet according to individual genotype, could influence the development and/or the treatment of cardiovascular diseases.

Objective: To evaluate the effect of three dietary approaches on metabolic, inflammatory and anthropometric profile in patients with CAD and possible interactions with polymorphisms in CD36 and STAT3 genes.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Dietary supplement: Control diet; Dietary supplement: Olive oil; Dietary supplement: Nuts

Detailed Description

A randomized clinical trial with a nutrigenetic approach among patients ≥ 40 years diagnosed with CAD. Randomization will be made in blocks from a list of random numbers generated by site www.randomization.org (sealed opaque envelopes). A questionnaire with demographic and clinical data will be applied; systolic and diastolic blood pressure, waist, hip and neck circumferences, height and weight will be assessed. Nutrients intake will be assessed through a food diary. Laboratory evaluation will consist of lipid profile (LDL-cholesterol, HDL-cholesterol and total cholesterol, serum triglycerides), glycemic profile (fasting plasma glucose, glycated hemoglobin) and inflammatory profile (high-sensitivity C-reactive protein, fibrinogen, TNF-alpha, interleukin-6 and interleukin-10). Genotyping will be made by TaqMan SNP Genotyping Assay®. Patients will be randomized in three groups: Group 1 Intervention [Supplementation with nuts (SN)]: standard dietary guidelines + 30g of nuts a day; Group 2 Intervention [Supplementation with olive oil (SAO)]: standard dietary guidelines + 30ml of olive oil a day; Group 3 [Control diet (CO)]: standard dietary guidelines. Patients will be followed for three months (12 weeks) and the primary endpoint will be the change in LDL-cholesterol. The follow-up visits will be made at 30 days, 60 days and 90 days (final visit).

• Study Type: Interventional
• Enrollment (Anticipated): 204
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90.620-001
      • Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with coronary arterial disease.

Exclusion Criteria:

• Psychiatric disease;
• Morbid obesity (BMI ≥ 40mg/m2);
• Expectancy of life less than 6 months;
• Pregnancy or lactation;
• Renal failure (in dialysis);
• Congestive heart failure;
• Prior organ transplantation;
• Patients in wheelchair;
• Use of vitamin/nutritional supplements;
• Chronic use of non steroidal anti-inflammatory drugs;
• Participation in another experimental study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control diet (standard dietary); Patients will receive a control diet based on standard dietary guidelines	Dietary supplement: Control diet; Diet based on standard guidelines
EXPERIMENTAL: Olive oil (30ml a day); Patients will receive a control diet based on standard dietary guidelines + 30ml of olive oil a day	Dietary supplement: Olive oil; 30ml a day of olive oil
EXPERIMENTAL: Nuts (30g a day); Patients will receive a control diet based on standard dietary guidelines plus 30g of nuts a day	Dietary supplement: Nuts; 30g a day of nuts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL	LDL-cholesterol, in mg/dL	twelve weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TC	total cholesterol (TC), in mg/dL)	twelve weeks
NHDL	non-HDL-cholesterol, in mg/dL	twelve weeks
HDL	HDL-cholesterol, in mg/dL	twelve weeks
TG	serum triglyceride, in mg/dL	twelve weeks
TyG index	Triglycerides/fasting glucose index, calculated according to (fasting triglycerides [mg/dL] x fasting glucose [mg/dL])/2	twelve weeks
HbA1C	glycated hemoglobin (HbA1C), in %	twelve weeks
FG	fasting glucose, in mg/dL	twelve weeks
Insulin	serum insulin, in UI/mL	twelve weeks
HOMA-IR	Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated according to fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5	twelve weeks
inflammatory profile	CRP-us, in mg/dL; IL-6, in mg/dL; IL-10, in mg/dL	twelve weeks
BW	body weight, in kg;	twelve weeks
BMI	body mass index (BMI), in kg/m2, calculated according to weight (kg)/height*height (m)	twelve weeks
WC	waist circumference, in cm	twelve weeks
NC	neck circumference, in cm	twelve weeks
LAP index	Lipid Accumulation Product Index (in cm.mmol.l), calculated for men: men (waist circumference [WC] - 65) x triglycerides (TG), and women (WC - 58) x TG	twelve weeks
DAAT index	Deep-Abdominal-Adipose-Tissue Index (in cm2), calculated for men (- 382.9 + [1.09 x weight] + [6.04 x waist circumference (WC)] + [- 2.29 x body mass index (BMI)]) and women (- 278 + [- 0.86 x weight] + [5.19 x WC])	twelve weeks
VAI index	Visceral Adiposity Index (log), calculated for men (waist circumference (WC)/[39 + (1.88 x body mass index (BMI)) x (triglycerides (TG)/1.03) x (1.31/HDL)]) and women (WC/[36.58 + (1.89 x BMI) x (TG/0.81) x (1.53/HDL)])	twelve weeks
PFA	plasma fatty acids, in percentage	twelve weeks
Mon	plasma monocytes, in percentage	twelve weeks
rs1761667 G>A	Polymorphism rs1761667 G>A in the CD36 gene	baseline
rs8069645 A>G	Polymorphism rs8069645 A>G in the STAT3 gene	baseline
Interaction diet * genotype	Interaction between dietary intervention, rs1761667 and rs8069645	twelve weeks

Collaborators and Investigators

• Sponsor: Instituto de Cardiologia do Rio Grande do Sul
• Collaborators: Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Investigators: Principal Investigator: Aline Marcadenti, PhD, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC); Study Director: Vera L Portal, PhD, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC); Study Director: Melissa M Markoski, PhD, Instituto De Cardiologia/Fundação Universitária De Cardiologia; Study Director: Alexandre S Quadros, PhD, Instituto De Cardiologia/Fundação Universitária De Cardiologia

Publications and helpful links

General Publications

• Dos Santos JL, Portal VL, Markoski MM, de Quadros AS, Bersch-Ferreira A, Marcadenti A. Effect of pecan nuts and extra-virgin olive oil on glycemic profile and nontraditional anthropometric indexes in patients with coronary artery disease: a randomized clinical trial. Eur J Clin Nutr. 2022 Jun;76(6):827-834. doi: 10.1038/s41430-021-01045-7. Epub 2021 Nov 22.
• Campos VP, Portal VL, Markoski MM, Quadros AS, Bersch-Ferreira AC, Garavaglia J, Marcadenti A. Effects of a healthy diet enriched or not with pecan nuts or extra-virgin olive oil on the lipid profile of patients with stable coronary artery disease: a randomised clinical trial. J Hum Nutr Diet. 2020 Jun;33(3):439-450. doi: 10.1111/jhn.12727. Epub 2019 Dec 19.
• Portal VL, Markoski MM, Quadros AS, Garofallo S, Santos JL, Oliveira A, Wechenfelder C, Campos VP, Souza PA, Machado L, Marcadenti A. Effect of polymorphisms in the CD36 and STAT3 genes on different dietary interventions among patients with coronary artery disease: study protocol for a randomized controlled trial. Trials. 2016 Sep 5;17(1):437. doi: 10.1186/s13063-016-1564-1.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): June 17, 2016
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: July 18, 2014
• First Submitted That Met QC Criteria: July 25, 2014
• First Posted (ESTIMATE): July 28, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Heart Diseases
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 48612013