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The Association of IL-6, TNFα and CRP Gene Polymorphisms with Coronary Artery Disease in a Tunisian Population: A
Nedra Grira1,2, Dhaker Lahidheb3,4, Oussama Lamine3,5
1Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia. nedra.grira@fst.utm.tn.
Insights
Genetic variations in Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNFα), and C-reactive protein (CRP) genes are associated with increased coronary artery disease (CAD) risk in the Tunisian population. These polymorphisms may serve as crucial susceptibility markers for CAD.
Area of Science:
- Cardiovascular Genetics
- Immunology
- Population Health
Background:
- Coronary artery disease (CAD) is recognized as an inflammatory condition.
- Systemic inflammation markers like Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNFα), and C-reactive protein (CRP) are linked to cardiovascular event risk.
- Investigating genetic susceptibility markers for CAD is crucial for understanding disease etiology.
Purpose of the Study:
- To evaluate the association of specific gene variants (IL-6 -174 G/C, TNFα -308 A/G, CRP +1059G/C) with CAD susceptibility in a Tunisian cohort.
- To determine if these polymorphisms act as risk factors for developing coronary artery disease.
Main Methods:
- A case-control study was conducted with 204 CAD patients and 400 controls from Tunisia.
- Genotyping of IL-6, TNFα, and CRP gene variants was performed using polymerase chain reaction and restriction fragment length polymorphism analysis.
- Clinical data including BMI, smoking history, lipid profiles, and inflammatory marker levels were analyzed.
Main Results:
- Significant differences in BMI, family history of CAD, smoking, TC, LDLc, hs-CRP, IL6, and TNFα levels were observed between CAD patients and controls.
- Specific genotypes showed significant differences: IL6-174CC (OR=7.71), TNFα -308 AA (OR=2.95), and CRP +1059 CC (OR=5.40) were associated with increased CAD risk.
- No association was found between these genotypes and the measured levels of inflammatory markers.
Conclusions:
- The IL-6 (-174 G/C), TNFα (-308 A/G), and CRP (+1059G/C) polymorphisms are identified as potential risk factors for coronary artery disease in the Tunisian population.
- These genetic variations may contribute to CAD susceptibility independent of their direct impact on circulating inflammatory marker levels.
Abstract:
Coronary artery disease is an inflammatory disease. Systemic markers of inflammation such as Interleukin-6, Tumor Necrosis Factor alpha and C-reactive protein have previously been shown to be associated with increased risk of cardiovascular events. The aim of the present study is to assess the role of variants in the IL-6 (- 174 G/C), TNFα (- 308 A/G) and CRP (+ 1059G/C) genes as susceptibility markers for CAD in a Tunisian population. The investigation was conducted as a case-control study involving 204 patients and 400 age-gender matched controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. There are significant differences between CAD patients and the control group with regard to BMI (p < 10-3) and family history of CAD (p < 10-3). The CAD patients are more likely to have a history of smoking (p < 10-3), have a higher value of TC (p = 0.003), LDLc (p = 0.016), hs-CRP (p = 0.01), IL6 (p < 10-3) and TNFα (p = 0.038). Our analysis showed significant differences between cases and controls in genotypic distribution of IL6-174CC (p = 0.003; OR = 7.71 CI (1.58-37.56)), TNFα - 308 AA (p = 0.004; OR = 2.95 (1.57-5.51)) and CRP + 1059 CC (p < 10-3; OR = 5.40 (2.30-12.68)). However, we failed to find an association between the different genotypes and the inflammatory markers levels. Our results suggest that the presence of IL-6 (- 174 G/C), TNFα (-308 A/G) and CRP (+ 1059G/C) polymorphisms, may be considered to be a risk factor for CAD in Tunisian population.
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