PMID- 10523338
OWN - NLM
STAT- MEDLINE
DCOM- 19991201
LR  - 20220408
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 34
IP  - 4 Pt 1
DP  - 1999 Oct
TI  - Genetic variants in the epithelial sodium channel in relation to aldosterone and 
      potassium excretion and risk for hypertension.
PG  - 631-7
AB  - Renin and aldosterone secretion is often lower in blacks than in whites,
      characteristics that resemble a milder form of Liddle syndrome in which a
      mutation in the amiloride-sensitive epithelial sodium channel (ENaC) of the
      kidney results in enhanced resorption of sodium. In the present study, we looked 
      for evidence that the intrinsic level of ENaC activity is indeed higher in blacks
      than in whites. In overnight urine samples collected from young people (249 white
      and 181 black subjects, mean age 13.4 years), the urinary aldosterone/potassium
      ratio, which is typically very low in Liddle syndrome, was lower in blacks than
      in whites: 0.421+/-0.024 (mean+/-SE) versus 0.582+/-0.016 nmol/mmol (P<0.0001).
      In addition, all but 1 of 5 molecular variants in ENaC were much more common in
      blacks than in whites. G442V in the beta-subunit, present in 16% of the blacks
      and in only 1 white, was associated with parameters reflective of a greater Na
      retention and potentially a higher ENaC activity: a lower plasma aldosterone
      concentration (P=0.070), a lower urinary aldosterone excretion rate (P=0.052), a 
      higher potassium excretion rate (P=0.048), and a lower urinary
      aldosterone/potassium ratio (P=0.027). In a second cohort consisting of 126 black
      and 161 white normotensive subjects and 232 black and 188 white hypertensive
      subjects, betaG442V did not show a significant association with hypertension
      (P=0.089). On the other hand, a variant that was twice as common in whites,
      alphaT663A, was associated with being normotensive both in blacks (P=0.018) and
      in whites (P=0.034). Expression of either betaG442V or alphaT663A in Xenopus
      oocytes did not result in a change in basal Na current, consistent with the
      variants being in linkage disequilibrium with alleles at active loci. In
      conclusion, several lines of evidence are presented to suggest that ENaC activity
      is higher in blacks than in whites, which could contribute to racial differences 
      in Na retention and the risk for hypertension.
FAU - Ambrosius, W T
AU  - Ambrosius WT
AD  - Department of Medicine, Indiana University School of Medicine , and the VA
      Medical Center, Indianapolis, Ind, USA.
FAU - Bloem, L J
AU  - Bloem LJ
FAU - Zhou, L
AU  - Zhou L
FAU - Rebhun, J F
AU  - Rebhun JF
FAU - Snyder, P M
AU  - Snyder PM
FAU - Wagner, M A
AU  - Wagner MA
FAU - Guo, C
AU  - Guo C
FAU - Pratt, J H
AU  - Pratt JH
LA  - eng
GR  - HL-03575/HL/NHLBI NIH HHS/United States
GR  - M01-RR00750/RR/NCRR NIH HHS/United States
GR  - R01-HL-35795/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Sodium Channels)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 3.4.23.15 (Renin)
RN  - RWP5GA015D (Potassium)
SB  - IM
EIN - Hypertension 2003 Jan;41(1):1e
MH  - Adolescent
MH  - Aldosterone/blood/*metabolism/urine
MH  - Blacks/genetics
MH  - Blood Pressure/genetics
MH  - Cohort Studies
MH  - Epithelial Cells/metabolism
MH  - Exons
MH  - Female
MH  - Humans
MH  - Hypertension/*genetics
MH  - Male
MH  - Potassium/blood/*metabolism/urine
MH  - Renin/metabolism
MH  - Risk Factors
MH  - Sodium Channels/*genetics/*metabolism
MH  - Whites/genetics
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1161/01.hyp.34.4.631 [doi]
PST - ppublish
SO  - Hypertension. 1999 Oct;34(4 Pt 1):631-7. doi: 10.1161/01.hyp.34.4.631.