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The role of NF-κB1A promoter polymorphisms on coronary artery disease risk
Nil Özbilüm1, Serdal Arslan, Öcal Berkan
1Department of Molecular Biology and Genetics, Faculty of Science, Cumhuriyet University, Sivas, Turkey.
Insights
The NF-κBIA-826TT genotype is a significant risk factor for coronary artery disease (CAD) in the Turkish population. This finding may serve as a valuable marker for CAD development and prevention strategies.
Area of Science:
- Genetics
- Cardiovascular Disease
- Immunology
Background:
- Coronary artery disease (CAD) is a leading global cause of mortality, recognized as a chronic inflammatory condition.
- Nuclear factor kappa B (NF-κB) is a key regulator of immune responses.
- NF-κB inhibitor alpha (NF-κBIA) plays a crucial role in modulating NF-κB activity.
Purpose of the Study:
- To investigate the association between CAD and specific polymorphisms in the NF-κBIA gene (-297 C/T, -826 C/T, -881 A/G) within a Turkish population.
- To determine if these NF-κBIA gene variants are risk factors for the development of CAD.
Main Methods:
- Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to analyze genotypes.
- The study included 201 patients diagnosed with CAD and 201 healthy controls from Turkey.
- Allele, genotype, and haplotype frequencies were compared between the case and control groups.
Main Results:
- No significant differences were observed for NF-κBIA-297 C/T and -881 A/G polymorphisms between CAD patients and controls.
- The NF-κBIA-826TT genotype frequency was significantly higher in CAD patients (p=0.015, adjusted OR=7.09).
- The NF-κBIA-826T allele carriage rate was also significantly higher in CAD patients (p=0.03, OR=1.43).
- Linkage analysis revealed close linkage among the three NF-κBIA variants, with specific haplotypes (TTG, TTA, TCG) associated with CAD risk.
Conclusions:
- The NF-κBIA-826TT genotype is identified as a significant risk factor for CAD in the studied Turkish population.
- This genotype may serve as a valuable genetic marker for predicting CAD development.
- Further research into the functional implications of NF-κBIA variants in CAD pathogenesis is warranted.
Abstract:
Coronary artery disease (CAD), which is now regarded as a chronic inflammatory disease, is the leading cause of death worldwide. Nuclear factor (NF)-κB is a transcription factor that plays an important role in the regulation of the immune system. NF-κBIA is the inhibitory version of NF-κB. This study is the first investigation of the association between CAD and NF-κBIA-297 C/T, -826 C/T, -881 A/G polymorphisms in a Turkish population using PCR-RFLP method. The study population comprised 201 cases with CAD and 201 healthy controls. There was no significant difference in NF-κB1A-297 C/T and -881 A/G in allele and genotype frequencies between case and control populations. The genotype frequency of NF-κBIA-826TT in the patients with CAD was significantly higher than that of the controls (p = 0.015, adjusted OR = 7.09, 95% CI = 1.95-25.70). The patients with CAD also had significantly higher carriage rate of NF-κBIA-826T allele than the controls (p = 0.03, OR = 1.43, 95% CI = 1.03-1.99). Linkage analysis indicated a close linkage among these three variants of NF-κBIA (for case, χ(2 ) = 85.35 and p < 0.001; for control, χ(2 ) = 21.58 p < 0.001) and TTG, TTA and TCG haplotypes were associated with CAD (adjusted OR = 2.54, 95% CI = 0.88-7.27; p = 0.001, adjusted OR = 1.61, 95% CI: 0.64-4.02; p = 0.04, adjusted OR = 0.08, 95% CI = 0.01-0.64; p < 0.001, respectively). NF-κBIA-826TT genotype may be a significant risk factor and a valuable marker for the development of CAD.
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