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

Takashi Eguchi, Tatsuya Maruyama, Yoichi Ohno, Toshiyuki Morii, Keiichi Hirao, Hiroshi Hirose, Hiroshi Kawabe, Ikuo Saito, Matsuhiko Hayashi, Takao Saruta

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The tumor necrosis factor (TNF)-α 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 χ2 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.

Original languageEnglish
Pages (from-to)775-779
Number of pages5
JournalHypertension Research
Issue number9
Publication statusPublished - 2009 Sep 18


ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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