Association of IL-1β +3953 C and HLA-DRB1*15 with Coronary Artery and Rheumatic Heart Diseases in South India
M S Sreekanth1, S K Esdan Basha1, G Arun Kumar2
1Department of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Chennai 603103, India.
Insights
This study found that specific human leukocyte antigen (HLA)-DRB1 alleles and interleukin-1 beta (IL-1β) gene variants are associated with cardiovascular diseases in South India. HLA-DRB1*14 and IL-1β +3953C increase risk for coronary artery disease, while HLA-DRB1*15 predisposes to rheumatic heart disease.
Area of Science:
- Genetics
- Cardiology
- Immunology
Background:
- Cardiovascular diseases (CVDs) are a major health concern globally.
- Specific genetic factors, including Human Leukocyte Antigen (HLA) alleles and cytokine gene polymorphisms, are implicated in CVD susceptibility.
- Understanding these genetic associations is crucial for risk stratification and targeted interventions.
Purpose of the Study:
- To investigate the association of HLA-DRB1* and IL-1β +3953C/T gene polymorphisms with Coronary Artery Disease (CAD) and Rheumatic Heart Disease (RHD) in a South Indian population.
- To analyze these associations in relation to clinical parameters, demographic factors, and specific ethnic groups.
Main Methods:
- A case-control study involving 323 CAD patients, 56 RHD patients, and 254 controls from South India.
- Genotyping of HLA-DRB1* and IL-1β +3953C/T polymorphisms using Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) and Amplification Refractory Mutation System - PCR (ARMS-PCR).
- Statistical analysis of genetic associations with clinical and demographic variables, including population stratification.
Main Results:
- The HLA-DRB1*14 allele showed a significant predisposition to CAD, particularly in males and those with Triple Vessel Disease.
- The HLA-DRB1*15 allele was significantly associated with RHD in both genders.
- The IL-1β +3953C allele demonstrated a high-risk association with CAD, especially in specific castes (Mudaliar and Vanniyar).
- Distinct genetic associations were observed for RHD (infectious etiology) and CAD (inflammatory disorder).
Conclusions:
- The study highlights varied genetic predispositions for RHD and CAD in the South Indian cohort.
- HLA-DRB1*14 and IL-1β +3953C are risk factors for CAD, while HLA-DRB1*15 is associated with RHD.
- These findings underscore the importance of genetic background in the pathogenesis of different cardiac diseases.
Abstract:
Among the various candidate genes predisposing for cardiovascular diseases, HLA-DRB1* and IL-1β +3953C/T alleles have been implicated repeatedly. To test these in South India, we carried out a case control study of 323 Coronary Artery Disease (CAD) patients, 56 Rheumatic Heart Disease (RHD) patients and 254 endemic controls. The polymorphisms were studied by PCR - SSP and ARMS-PCR methods and results analyzed for various clinical and demographic parameters. In CAD, HLA-DRB1*14 allele showed significant predisposition (OR: 2.19; 95% CI: 1.04-4.58; p value=0.023), particularly in male patients (OR: 4.07; 95% CI: 1.20-13.81; p value=0.01) and further in males with Triple Vessel Disease (OR: 5.49; 95% CI: 1.45-20.60; p value=0.007). On the other hand, HLA-DRB1*15 predisposed for RHD (OR: 3.56; 95% CI: 1.87-6.78; p value=0.001) in both the genders. Population stratification showed this higher risk association in Vanniyar caste (OR: 5.00; 95% CI: 1.27-19.59; p value=0.022). Among the IL1-β +3953C/T polymorphism, the ancestral allele 'C' showed a significant high risk association with CAD (OR: 1.83; 95% CI: 1.24-2.70; p value=0.001), particularly in Mudaliar (OR: 6.07; 95% CI: 1.77-20.74; p value=0.003; AF=0.7) and Vanniyar castes (OR: 3.67; 95% CI: 0.92-14.57; p value=0.05; AF=0.660). Two different cardiac ailments studied, RHD & CAD thus showed varied associations in this South Indian cohorts. RHD having an infectious aetiology shared a HLA-DRB1*15 high risk association, while HLA-DRB1*14 and IL-1β +3953C predisposed for CAD, an inflammatory disorder, reiterating the diverse genetic predisposition of the two cardiac ailments studied.
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