Polymorphism of Nrf2, an Antioxidative Gene, is Associated with Blood Pressure and Cardiovascular Mortality in Hemodialysis Patients

被引:48
作者
Shimoyama, Yasuhiko [1 ]
Mitsuda, Yoko [2 ]
Tsuruta, Yoshinari [3 ]
Hamajima, Nobuyuki [4 ]
Niwa, Toshimitsu [1 ,5 ]
机构
[1] Nagoya Univ, Grad Sch Med, Dept Adv Med Uremia, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Prevent Med, Showa Ku, Nagoya, Aichi 4668550, Japan
[3] Meiyo Clin, Aichi, Japan
[4] Nagoya Univ, Grad Sch Med, Dept Healthcare Adm, Showa Ku, Nagoya, Aichi 4668550, Japan
[5] Shubun Univ, Fac Hlth & Nutr, Ichinomiya, Aichi 4910938, Japan
来源
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES | 2014年 / 11卷 / 07期
关键词
Nrf2; polymorphism; hemodialysis; blood pressure; cardiovascular mortality; TRANSCRIPTION FACTOR NRF2; OXIDATIVE STRESS; LUNG INJURY; IN-VIVO; PROTECTION; MICE; EXPRESSION; ATHEROSCLEROSIS; INFLAMMATION; RESPONSES;
D O I
10.7150/ijms.8590
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Nrf2 is a transcription factor that regulates the expression of antioxidant genes. This study aimed to investigate the association of Nrf2 gene single nucleotide polymorphisms (SNPs), rs35652124 (-653A/G) and rs6721961 (-617C/A), with laboratory data and mortality in hemodialysis (HD) patients. Methods: Blood samples were obtained from 216 HD patients (119 males and 97 females; 60 diabetics and 156 non-diabetics) with mean age of 60.3 +/- 13.3 (SD) years, and mean HD duration of 9.10 +/- 8.28 years. Genotyping was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay. Results: As for rs35652124, diastolic blood pressure (BP) was significantly high in total AA carriers. beta 2-microglobulin was significantly low in male AA carriers. Systolic BP, diastolic BP and albumin were significantly high in female AA carriers. As for 6721961, systolic BP and diastolic BP were significantly high in female AA carriers. Cox proportional hazard analysis adjusted for age, HD duration, diabetes and Kt/V demonstrated that rs35652124 AA carriers showed higher cardiovascular mortality than (GG+GA) carriers. Conclusion: Nrf2 SNPs were associated with BP in Japanese HD patients. More notably, rs35652124 was associated with cardiovascular mortality in these patients.
引用
收藏
页码:726 / 731
页数:6
相关论文
共 25 条
  • [1] NF-E2-Related Factor 2 Promotes Atherosclerosis by Effects on Plasma Lipoproteins and Cholesterol Transport That Overshadow Antioxidant Protection
    Barajas, Berenice
    Che, Nam
    Yin, Fen
    Rowshanrad, Amir
    Orozco, Luz D.
    Gong, Ke Wei
    Wang, Xuping
    Castellani, Lawrence W.
    Reue, Karen
    Lusis, Aldons J.
    Araujo, Jesus A.
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2011, 31 (01) : 58 - +
  • [2] Nrf2 is essential for protection against acute pulmonary injury in mice
    Chan, KM
    Kan, YW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) : 12731 - 12736
  • [3] The transcription factor NRF2 protects against pulmonary fibrosis
    Cho, HY
    Reddy, SPM
    Yamamoto, M
    Kleeberger, SR
    [J]. FASEB JOURNAL, 2004, 18 (09) : 1258 - +
  • [4] Role of NRF2 in protection against hyperoxic lung injury in mice
    Cho, HY
    Jedlicka, AE
    Reddy, SP
    Kensler, TW
    Yamamoto, M
    Zhang, LY
    Kleeberger, SR
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2002, 26 (02) : 175 - 182
  • [5] The NRF2 gene variant,-653G/A, is associated with nephritis in childhood-onset systemic lupus erythematosus
    Cordova, E. J.
    Velazquez-Cruz, R.
    Centeno, F.
    Baca, V.
    Orozco, L.
    [J]. LUPUS, 2010, 19 (10) : 1237 - 1242
  • [6] Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase 1 gene
    Dhakshinamoorthy, S
    Jaiswal, AK
    [J]. ONCOGENE, 2001, 20 (29) : 3906 - 3917
  • [7] High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes
    Enomoto, A
    Itoh, K
    Nagayoshi, E
    Haruta, J
    Kimura, T
    O'Connor, T
    Harada, T
    Yamamoto, M
    [J]. TOXICOLOGICAL SCIENCES, 2001, 59 (01) : 169 - 177
  • [8] Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping
    Hamajima, N
    Saito, T
    Matsuo, K
    Kozaki, K
    Takahashi, T
    Tajima, K
    [J]. JAPANESE JOURNAL OF CANCER RESEARCH, 2000, 91 (09): : 865 - 868
  • [9] Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease
    Heitzer, T
    Schlinzig, T
    Krohn, K
    Meinertz, T
    Münzel, T
    [J]. CIRCULATION, 2001, 104 (22) : 2673 - 2678
  • [10] Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
    Itoh, K
    Wakabayashi, N
    Katoh, Y
    Ishii, T
    Igarashi, K
    Engel, JD
    Yamamoto, M
    [J]. GENES & DEVELOPMENT, 1999, 13 (01) : 76 - 86