Molecular & Cellular Toxicology

, Volume 8, Issue 3, pp 257–262

Association between CD40 promoter polymorphism (rs1800686, −508 C/T) and ischemic stroke with hypertension in a Korean population

  • Jin-Man Cho
  • Bong-Keun Choe
  • Renhua Zheng
  • Jinmann Chon
  • Seung Don Yoo
  • Chong-Jin Kim
  • Geum-hee Gwak
  • Sung-Vin Yim
Original Paper

DOI: 10.1007/s13273-012-0031-7

Cite this article as:
Cho, JM., Choe, BK., Zheng, R. et al. Mol. Cell. Toxicol. (2012) 8: 257. doi:10.1007/s13273-012-0031-7

Abstract

Although glutamate toxicity is important in stroke injury, the immune and inflammatory systems are also related to stroke pathogenesis. Tumor necrosis factor (TNF) receptor superfamily member 5 (CD40) plays a crucial role in mediating a broad variety of immune and inflammatory responses. To investigate whether CD40 polymorphisms are associated with the development of ischemic stroke, two promoter single nucleotide polymorphisms (SNPs) of the CD40 gene (rs1800686, −508A/G; rs752118, −173C/T) were analyzed in 121 patients with ischemic stroke (IS) and 291 control subjects. All stroke patients were classified into clinical subgroups according to their blood pressure levels (hypertension, present and absent), fasting plasma glucose (diabetes mellitus, present and absent), and lipids (dyslipidemia, present and absent). SNPStats and SNPAnalyzer Pro software were used to obtain odds ratios (ORs), 95% confidence intervals (CIs), and Pvalues. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were used to analyze the genetic data. The two tested CD40 promoter SNPs (rs1800686 and rs752118) were not associated with the development of IS, but the GT haplotype of these two SNPs was associated with the development of IS (P= 0.0148). The rs1800686 SNP frequency differed between IS patients without hypertension and those with hypertension (P=0.017, OR=0.17, 95% CI=0.04–0.72 in the codominant2 model; P=0.023, OR=0.37, 95% CI=0.15–0.90 in the dominant model; P=0.0085, OR=0.42, 95% CI=0.21–0.81 in the log-additive model; P=0.011, OR=0.47, 95% CI=0.27–0.85 in allele frequencies). The A allele frequency of rs1800686 was lower in IS patients with hypertension (27.2%) than in IS patients with hypertension (44.3%), while the G allele frequency of rs1800686 was higher in IS patients with hypertension (72.8%) than in IS patients with hypertension (55.7%). These results suggest that the GT haplotype of rs1800686 and rs752118 in the CD40 gene may be associated with the development of IS, and rs1800686 may contribute to IS in Korean patients with hypertension.

Keywords

CD40 Hypertension Ischemic stroke Pathogenesis Single nucleotide polymorphism Toxicity 

Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Jin-Man Cho
    • 1
  • Bong-Keun Choe
    • 2
  • Renhua Zheng
    • 3
  • Jinmann Chon
    • 4
  • Seung Don Yoo
    • 4
  • Chong-Jin Kim
    • 1
  • Geum-hee Gwak
    • 5
  • Sung-Vin Yim
    • 2
    • 3
  1. 1.Division of Cardiology, Department of Internal Medicine, School of MedicineKyung Hee UniversitySeoulKorea
  2. 2.Kohwang Medical Research InstituteKyung Hee UniversitySeoulKorea
  3. 3.Department of Clinical Pharmacology, School of MedicineKyung Hee UniversitySeoulKorea
  4. 4.Department of Physical Medicine & Rehabilitation, School of MedicineKyung Hee UniversitySeoulKorea
  5. 5.Department of Biochemistry and Molecular Biology, School of MedicineKyung Hee UniversitySeoulKorea

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