Haplotype-based case-control study on human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 gene and essential hypertension.
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.
Naganuma
Takahiro
T
Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
Nakayama
Tomohiro
T
Sato
Naoyuki
N
Fu
Zhenyan
Z
Soma
Masayoshi
M
Yamaguchi
Mai
M
Shimodaira
Masanori
M
Aoi
Noriko
N
Usami
Ron
R
D000368:Aged; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014157:Transcription Factors
D008055:Lipids; D014157:Transcription Factors; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase