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An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
ADA gene haplotype is associated with coronary-in-stent-restenosis
Morteza Gholami1, Sepideh Borhan Dayani2, Maryam Mehrpooya3
1Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Insights
The Adenosine Deaminase (ADA) gene A allele (rs452159) and GA haplotype may reduce the risk of in-stent restenosis (ISR) in cardiovascular disease patients. Further studies are recommended for ISR risk assessment.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Research
- Pharmacogenomics
Background:
- Cardiovascular diseases (CVDs) are a leading global cause of mortality.
- The role of Adenosine Deaminase (ADA) gene variants in in-stent restenosis (ISR) remains understudied.
- ISR is a significant complication following angioplasty with stenting.
Purpose of the Study:
- To investigate the association of ADA gene variants with the risk of ISR.
- To evaluate the genetic and haplotype-based risk of ISR.
- To explore potential genetic markers for ISR risk assessment.
Main Methods:
- Genotyping of ADA gene polymorphisms G22A (rs73598374) and A4223C (rs452159) using PCR-RFLP.
- Analysis of 91 patients (40 ISR+ and 51 ISR-) with coronary artery disease (CAD).
- Statistical analysis using SPSS v. 20 and Haploview 4.2 software for genetic and haplotype models.
Main Results:
- The A allele of ADA rs452159 polymorphism was significantly associated with a decreased risk of ISR (OR=0.366, P=0.028).
- No significant association was found for the rs73598374 polymorphism with ISR risk.
- The GA haplotype (rs73598374/rs452159) also showed a protective effect against ISR (OR=0.382, P=0.025).
Conclusions:
- The A allele of ADA rs452159 and the GA haplotype may be protective factors against ISR in patients receiving drug-eluting stents.
- These findings suggest a potential role for ADA variants in ISR risk stratification.
- Further observational studies in diverse populations are warranted to validate these findings and develop a comprehensive ISR risk assessment panel.
Background:
Cardiovascular diseases (CVDs) are the most common and the first cause of death worldwide. While some studies have investigated the association of the Adenosine Deaminase (ADA) gene with CDVs, its roles on in-stent restenosis (ISR) has not been studied.
Methods And Results:
In this study, we investigated the role of ADA gene variants in both genetic and haplotype models on the risk of ISR. 91 samples were included in this study. The subjects were divided into two groups regarding having or not-having ISR (n = 40 ISR+ and n = 51 ISR-). The genotyping for G22A (rs73598374) and A4223C (rs452159) polymorphisms was performed using PCR-RFLP method. Statistical analysis was performed by SPSS v. 20 and Haploview 4.2 softwares. The basic demographic conditions in ISR groups were statistically similar. There was a significant association between A allele of rs452159 ISR groups after adjustment (allelic model: P value = 0.028, OR(95%CI) = 0.366(0.149-0.899)), while rs73598374 polymorphism shows no significant association with ISR. In haplotype analysis, the GA (G:rs73598374/A:rs452159) haplotype decreased the risk of ISR (P value = 00.025, OR(95%CI) = 0.382(0.161-0.907)).
Conclusions:
This study suggests that A allele of ADA rs452159 polymorphism and GA (G:rs73598374/A:rs452159) haplotype may be related to decreased risk of ISR in CAD patients receiving drug-eluting stent and offers more observational studies on ADA variants in other populations to generate a potential haplotype panel for ISR risk assessment.
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