Genetic Polymorphisms rs699947, rs1570360, and rs3025039 on the VEGF Gene Are Correlated with Extracranial Internal Carotid Artery Stenosis and Ischemic Stroke

  1. Byoung-Soo Shin9,10,11
  1. 1Department of Biochemistry, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal, Korea
  2. 2Clinical Trial Center for Functional Food, Chonbuk National University Hospital, Jeonju, Korea
  3. 3Department of Neurology, Wonkwang University School of Medicine, Iksan, Korea
  4. 4Department of Neurology, Chonnam National University Medical School and Hospital, Gwangju, Korea
  5. 5Department of Neurology, Chosun University School of Medicine and Hospital, Gwangju, Korea
  6. 6Department of Neurology, GoodMorning Hospital, Gwangju, Korea
  7. 7Department of Neurology, Hoseong Jeonju Hospital, Jeonju, Korea
  8. 8Department of Neurology, Gwangju General Hospital, Gwangju, Korea
  9. 9Department of Neurology, Chonbuk National University Medical School and Hospital, Jeonju, Korea
  10. 10Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
  11. 11Honam Stroke Research Society, Korea
  1. Address correspondence to Dr. Byoung-Soo Shin, Department of Neurology, Chonbuk National University Medical School, 20, Geonji-ro, Jeonju, Chonbuk, 54907, Korea; phone: +82 63 250 1896;, fax: +82 63 251 9363; e mail: sbsoo{at}jbnu.ac.kr
  1. * These authors contributed equally to this study.

Abstract

Extracranial internal carotid artery (ECICA) stenosis is a modifiable risk factor of ischemic stroke. VEGF plays a crucial role in the maintenance of endothelial integrity and physiological function. This study was designed to assess the correlations of VEGF polymorphisms with ECICA stenosis in ischemic stroke and to explore the relationships between these polymorphisms and different biochemical parameters. This study included a total of 650 ischemic stroke patients, 232 with ECICA stenosis while 418 had no ECICA stenosis as assessed by magnetic resonance angiography. Three SNPs in the VEGF gene, rs699947, rs1570360, and rs3025039, were assessed by real-time PCR coupled with melting curve analysis. Serum samples were analyzed for biochemical parameters in an automated clinical chemistry analyzer in the Laboratory Medicine Department. The CA and CA+AA (A allele bearing) genotype frequencies of the rs699947 polymorphism (AOR=1.46 and 1.47, respectively) and the GA genotype frequency of the rs1570360 polymorphism (AOR=7.33) showed a significant association with ECICA stenosis. However, the haplotype frequencies of C-A-A, T-A-C, and T-A-A (rs302503-rs1570360-rs699947) were significantly different between patients who experienced stroke with and stroke without ECICA stenosis. We found that the total homocysteine (tHcy) levels of stroke patients with ECICA stenosis with rs1570360 and rs699947 SNPs were significantly different compared to the wild-type reference genotype. In conclusion, VEGF rs699947 and rs3025039 polymorphisms were associated with increased risk of stroke, while rs1570360 and rs699947 were associated with stroke and ECICA stenosis.

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