DNA repair gene polymorphism is associated with the genetic basis of atherosclerotic coronary artery disease

Bazo, Ana Paula; Salvadori, Décio; Salvadori, Ricardo A.F.; Sodré, Luciandro P.; da Silva, Glenda N.; de Camargo, Elaine A.; Ribeiro, Lúcia R.; Salvadori, Daisy Maria Fávero

doi:10.1016/j.carpath.2009.12.004

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Volume 20, Issue 1 , Pages e9-e15, January 2011

DNA repair gene polymorphism is associated with the genetic basis of atherosclerotic coronary artery disease

Ana Paula Bazo
- Department of Pathology, Botucatu Medical School, UNESP, São Paulo State University, São Paulo, SP, Brazil
Décio Salvadori Jr
- Beneficência Portuguesa Hospital, São Paulo, SP, Brazil
Ricardo A.F. Salvadori
- São Luiz Hospital, São Paulo, SP, Brazil
Luciandro P. Sodré
- Department of Pathology, Botucatu Medical School, UNESP, São Paulo State University, São Paulo, SP, Brazil
Glenda N. da Silva
- Department of Pathology, Botucatu Medical School, UNESP, São Paulo State University, São Paulo, SP, Brazil
Elaine A. de Camargo
- Department of Pathology, Botucatu Medical School, UNESP, São Paulo State University, São Paulo, SP, Brazil
Lúcia R. Ribeiro
- Department of Pathology, Botucatu Medical School, UNESP, São Paulo State University, São Paulo, SP, Brazil
Daisy Maria Fávero Salvadori
- Department of Pathology, Botucatu Medical School, UNESP, São Paulo State University, São Paulo, SP, Brazil
- Corresponding author. Faculdade de Medicina de Botucatu, UNESP, Rubião Junior, 18618-000 Botucatu, SP, Brazil. Tel.: +55 14 38117263.

Received 13 October 2009; received in revised form 27 November 2009; accepted 18 December 2009. published online 21 January 2010.

Abstract

Background

Atherosclerotic coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. It is nowadays accepted that increased levels of DNA damage induced by xenobiotics play an important role in the early phases of atherogenesis. Therefore, in this study, we focus on determining whether genetic variations in xenobiotic-metabolizing [glutathione-S-transferase theta 1 (GSTT1), glutathione-S-transferase mu 1 (GSTM1), cytochrome P450 IIEI (CYP2E1)] and DNA repair [X-ray cross-complementing group 1 (XRCC1)] genes might be associated with increased risk for CAD.

Methods

A case-control study was conducted with 400 individuals who underwent subjected to coronary angiography. A total of 299 were patients diagnosed with effective coronary atherosclerosis (case group; >20% obstructive lesion), and 101 (control group) were individuals diagnosed as negative for CAD (<20% obstructive lesions). The polymorphism identifications for GSTM1 and GSTT1, and for CYP2E1 and XRCC1 genes were performed by polymerase chain reaction (PCR) amplification and by PCR-RFLP, respectively.

Results and conclusions

The XRCC1 homozygous wild-type genotype Arg/Arg for codon 399 was statistically less pronounced in the case subjects (21.4%) than in controls (38.5%); individuals with the variant XRCC1 genotype had a 2.3-fold increased risk for coronary atherosclerosis than individuals with the wild-type genotype (OR=2.3, 95% CI=1.13–4.69). Conversely, no association between GSTM1, GSTT1, and CYP2E1gene polymorphisms and coronary atherosclerosis was detected. The results provide evidence of the role of DNA damage and repair in cardiovascular disease.

Keywords: Atherosclerosis, Gene polymorphisms, XRCC1, CYP2E1, GSTM1, GSTT1