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Haplotype-based case-control study on human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 gene and essential hypertension
- Source :
- American journal of hypertension. 23(2)
- Publication Year :
- 2009
-
Abstract
- BACKGROUND Oxidative DNA damage is involved in the pathophysiology of essential hypertension (EH), which is a multifactorial disorder. Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/REF-1) is an essential endonuclease in the base excision repair pathway of oxidatively damaged DNA, in addition to having reducing properties that promote the binding of redox-sensitive transcription factors. Blood pressure in APE1/REF-1-knockout mice is reported to be significantly higher than in wild-type mice. The aim of this study was to investigate the relationship between EH and the human APE1/REF-1 gene through a haplotype-based case-control study using single-nucleotide polymorphisms (SNPs). METHODS We selected five SNPs in the human APE1/REF-1 gene (rs1760944, rs3136814, rs17111967, rs3136817, and rs1130409), and performed case-control studies in 265 EH patients and 266 age-matched normotensive (NT) subjects. RESULTS rs17111967 was found to show nonheterogeneity among Japanese subjects. There were no significant differences in the overall distribution of genotypes or alleles for each SNP between EH and NT groups. In the overall distribution of the haplotype-based case-control study constructed based on rs1760944, rs3136817, and rs1130409, the frequency of the G-T-T haplotype was significantly higher in the EH group than in the NT group (2.1% vs. 0.0%, P = 0.001). Multiple logistic regression analysis also revealed significant differences for the G-T-T haplotype, even after adjustment for confounding factors (OR = 8.600, 95% CI: 1.073-68.951, P = 0.043). CONCLUSIONS Based on the present results, the G-T-T haplotype appears to be a genetic marker of EH, and the APE1/REF-1 gene appears to be a susceptibility gene for EH.
- Subjects :
- Male
Genotype
Single-nucleotide polymorphism
Blood Pressure
Biology
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Japan
Risk Factors
Internal Medicine
DNA-(Apurinic or Apyrimidinic Site) Lyase
Humans
AP site
Allele
Gene
Alleles
Aged
Genetics
Reverse Transcriptase Polymerase Chain Reaction
Haplotype
Base excision repair
Middle Aged
Lipids
Logistic Models
Haplotypes
Genetic marker
Case-Control Studies
Hypertension
Female
DNA Damage
Transcription Factors
Subjects
Details
- ISSN :
- 19417225
- Volume :
- 23
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of hypertension
- Accession number :
- edsair.doi.dedup.....c5c56583a7ba9e9242b042a604eb2f48