• 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).

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.

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).

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.

American Journal of Hypertension 2010; doi:10.1038/ajh.2009.221

Takahiro Naganuma^1,2, Tomohiro Nakayama^1,3, Naoyuki Sato^1,3, Zhenyan Fu^1,4, Masayoshi Soma⁵, Mai Yamaguchi¹, Masanori Shimodaira³, Noriko Aoi¹ and Ron Usami²

• ¹Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan
• ²Department of Biological Applied Chemistry, Toyo University Graduate School of Engineering, Saitama, Japan
• ³Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
• ⁴Department of Cardiovascular Medicine, First Affiliated Hospital, Xinjiang Medical University, Urumqi, China
• ⁵Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

Correspondence: Tomohiro Nakayama, (tnakayam@med.nihon-u.ac.jp)