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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Dietary Supplement: Olive oil
* Dietary Supplement: Nuts
* Dietary Supplement: Control diet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control diet (standard dietary)<br>Patients will receive a control diet based on standard dietary guidelines | Dietary Supplement: Control diet<br>* Diet based on standard guidelines<br>|
| Experimental: Olive oil (30ml a day)<br>Patients will receive a control diet based on standard dietary guidelines + 30ml of olive oil a day | Dietary Supplement: Olive oil<br>* 30ml a day of olive oil<br>|
| Experimental: Nuts (30g a day)<br>Patients will receive a control diet based on standard dietary guidelines plus 30g of nuts a day | Dietary Supplement: Nuts<br>* 30g a day of nuts<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Diseases