Possible association of tumor necrosis factor receptor 2 gene polymorphism with severe hypertension using the extreme discordant phenotype design

被引:6
作者
Eguchi, Takashi [1 ]
Maruyama, Tatsuya [1 ]
Ohno, Yoichi [1 ,2 ]
Morii, Toshiyuki [1 ]
Hirao, Keiichi [1 ]
Hirose, Hiroshi [3 ]
Kawabe, Hiroshi [3 ]
Saito, Ikuo [3 ]
Hayashi, Matsuhiko [1 ]
Saruta, Takao [1 ]
机构
[1] Keio Univ, Sch Med, Dept Internal Med, Moroyama, Saitama 3500495, Japan
[2] Saitama Med Univ, Community Hlth Sci Ctr, Saitama, Japan
[3] Keio Univ, Ctr Hlth, Yokohama, Kanagawa 223, Japan
关键词
extreme discordant phenotypes; insulin resistance and C-reactive protein; soluble tumor necrosis factor receptor 2; INSULIN-RESISTANCE; BLOOD-PRESSURE; ARTERIAL STIFFNESS; ADIPOSE-TISSUE; FACTOR-ALPHA; DISEASE; OBESITY; INFLAMMATION; SENSITIVITY; MECHANISMS;
D O I
10.1038/hr.2009.91
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The tumor necrosis factor (TNF)-alpha pathway has a key role in regulating insulin resistance. TNF receptor 2 (TNFR2) is an emerging candidate gene for insulin resistance in essential hypertension. We examined the association of insulin resistance and enhanced TNF pathway with severe hypertension and the association of a microsatellite polymorphism of the TNFR2 gene with severe hypertension. Male severe essential hypertensive patients (HT) with the onset before 60 years of age and with genetic predispositions to hypertension were consecutively enrolled at our outpatient department (N=92). Normotensive men (NT) over 50 years of age were randomly registered from the participants in the annual health check program (N=78). Patients were selected as HT and NT who met stringent criteria for systolic/diastolic blood pressure (SBP/DBP) levels >= 180 and/or 110 mm Hg and <120/80 mm Hg, respectively. HT revealed significantly higher plasma insulin levels, C-reactive protein (CRP) and soluble fraction of TNFR2 concentrations (sTNFR2) than NT. A microsatellite polymorphism of the CA repeat in intron 4 of the TNFR2 gene was analyzed. The allele frequency of CA16 in HT differed significantly from that in NT (66/184 vs. 36/156, P=0.01 by chi(2) analysis). In HT, the CA16 carriers showed significantly higher SBP and plasma insulin levels and a higher tendency of sTNFR2 than did those without this allele. In NT, CA16 carriers revealed significantly higher sTNFR2 and CRP levels than did the CA16 non-carriers. These results suggest that the TNFR2 gene locus has a potential effect on developing severe hypertension through the augmented TNF pathway and insulin resistance. Hypertension Research (2009) 32, 775-779; doi: 10.1038/hr.2009.91; published online 26 June 2009
引用
收藏
页码:775 / 779
页数:5
相关论文
共 33 条
  • [1] STABILIZATION OF THE BIOACTIVITY OF TUMOR-NECROSIS-FACTOR BY ITS SOLUBLE RECEPTORS
    ADERKA, D
    ENGELMANN, H
    MAOR, Y
    BRAKEBUSCH, C
    WALLACH, D
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (02) : 323 - 329
  • [2] CA-repeat polymorphism in intron 1 of HSD11B2 - Effects on gene expression and salt sensitivity
    Agarwal, AK
    Giacchetti, G
    Lavery, G
    Nikkila, H
    Palermo, M
    Ricketts, M
    McTernan, C
    Bianchi, G
    Manunta, P
    Strazzullo, P
    Mantero, F
    White, PC
    Stewart, PM
    [J]. HYPERTENSION, 2000, 36 (02) : 187 - 194
  • [3] Signalling pathways of the TNF superfamily: A double-edged sword
    Aggarwal, BB
    [J]. NATURE REVIEWS IMMUNOLOGY, 2003, 3 (09) : 745 - 756
  • [4] Mechanisms of egfr gene transcription modulation:: Relationship to cancer risk and therapy response
    Brandt, Burkhard
    Meyer-Staeckling, Soenke
    Schmidt, Hartmut
    Agelopoulos, Konstantin
    Buerger, Horst
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (24) : 7252 - 7260
  • [5] INSULIN RESISTANCE - A MULTIFACETED SYNDROME RESPONSIBLE FOR NIDDM, OBESITY, HYPERTENSION, DYSLIPIDEMIA, AND ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE
    DEFRONZO, RA
    FERRANNINI, E
    [J]. DIABETES CARE, 1991, 14 (03) : 173 - 194
  • [6] Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance
    Fernández-Real, JM
    Broch, M
    Ricart, W
    Casamitjana, R
    Gutierrez, C
    Vendrell, J
    Richart, C
    [J]. DIABETES, 1998, 47 (11) : 1757 - 1762
  • [7] Insulin resistance and chronic cardiovascular inflammatory syndrome
    Fernández-Real, JM
    Ricart, W
    [J]. ENDOCRINE REVIEWS, 2003, 24 (03) : 278 - 301
  • [8] Shedding of TNF-α receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus
    Fernandez-Real, JM
    Lainez, B
    Vendrell, J
    Rigla, M
    Castro, A
    Peñarroja, G
    Broch, M
    Pérez, A
    Richart, C
    Engel, P
    Ricart, W
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2002, 282 (04): : E952 - E959
  • [9] Polymorphism of the tumor necrosis factor-α receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients
    Fernández-Real, JM
    Vendrell, J
    Ricart, W
    Broch, M
    Gutiérrez, C
    Casamitjana, R
    Oriola, J
    Richart, C
    [J]. DIABETES CARE, 2000, 23 (06) : 831 - 837
  • [10] Linkage and association of tumor necrosis factor receptor 2 locus with hypertension, hypercholesterolemia and plasma shed receptor
    Glenn, CL
    Wang, WYS
    Benjafield, AV
    Morris, BJ
    [J]. HUMAN MOLECULAR GENETICS, 2000, 9 (13) : 1943 - 1949