Association between two polymorphisms in the HLA-G gene and angiographic coronary artery disease
Chiara Boiocchi1, Sara Bozzini, Michele Zorzetto
1Laboratory of Immunogenetics, Department of Genetics and Microbiology, University of Pavia, Pavia, Italy. chiara.boiocchi@unipv.it
Insights
The human leukocyte antigen-G (HLA-G) gene
Area of Science:
- Immunogenetics
- Cardiovascular Disease Research
Background:
- Atherosclerosis is a leading cause of death globally.
- Cardiac inflammation plays a key role in atherosclerosis.
- Human Leukocyte Antigen-G (HLA-G) gene polymorphisms may influence disease susceptibility.
Purpose of the Study:
- To investigate the association between HLA-G gene polymorphisms (rs16375 and rs1632933) and coronary artery disease (CAD).
Main Methods:
- Polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and real-time PCR were used.
- Genotyping of 664 CAD patients and 345 controls for HLA-G polymorphisms.
- Analysis of allelic, genotypic, and haplotypic frequencies.
Main Results:
- The Ins/Ins genotype frequency of the 14-bp insertion/deletion (rs16375) polymorphism was significantly higher in CAD patients.
- The homozygous Ins/Ins genotype was independently associated with angiographic CAD (OR 2.09, P=0.03).
Conclusions:
- The homozygous Ins/Ins genotype of the HLA-G 14-bp insertion/deletion polymorphism is a novel risk factor for coronary artery disease.
- This finding contributes to understanding the genetic basis of this multifactorial inflammatory condition.
Abstract:
Atherosclerosis and related complications still represent the major cause of morbidity and mortality in industrialized countries. Therefore, it is particularly important to investigate the molecules involved in cardiac inflammation. Evidence exists showing that the human leukocyte antigen‑G (HLA-G) gene tissue expression and related protein physiological significance is influenced by two polymorphisms, rs16375 and rs1632933. In this study, allelic, genotypic and haplotypic frequencies of a 14-bp insertion/deletion (Ins/Del) (rs16375) and of rs1632933 polymorphisms of the HLA-G gene were investigated in 664 patients with coronary artery disease (CAD) and 345 matched controls by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and real-time PCR. The frequency of the Ins/Ins genotype was significantly higher in patients with CAD compared to the controls (P=0.018). After analysis of confounding variables, the results showed that the homozygous Ins/Ins was significantly and independently associated with the presence of angiographic CAD (odds ratio 2.09, 95% confidence interval 1.10-4.02, P=0.03). Our data demonstrate a new risk factor for this multifactorial inflammatory disease.
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