Poster Session I (PI 1-106)Displayed 8:00 am – 3:00 ... - Nature

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effect was lost at a concentration of 1 μM, with only K demonstrating the
significant inhibition of efflux, which was confirmed by patch-clamp.
CONCLUSION: The data demonstrate that the K metabolites
partially (40% relative to nicotine) stimulated the α3β4 NR at 100 nM
concentrations and this effect was lost at higher concentrations. The
observed stimulation was inhibited by the NR antagonist mecamylamine
indicating that this was mediated by NR. In addition, the inhibition of
Rb efflux was only seen for K, with weak inhibition by NK, HK1 and
HNK. While for the α7 NR, weak inhibition was observed for all metabolites
except DHNK, which had a pronounced effect, suggesting subtype
selectivity for K and DHNK for NR. The variability observed in treatment
response in depressed patients and chronic pain patients may be
due to individual differences in the metabolism of K.
PI-22
HYPERTENSION SUSCEPTIBILITY LOCI ASSOCIATED
WITH BLOOD PRESSURE RESPONSE TO ANTIHYPERTEN-
SIVES- RESULTS FROM THE PHARMACOGENOMIC EVALU-
ATION OF ANTIHYPERTENSIVE RESPONSES (PEAR) STUDY.
Y. Gong, 1 C. W. McDonough, 1 Z. Wang, 2 R. M. Cooper-DeHoff, 1
T. Y. Langaee, 1 A. L. Beitelshee, 3 S. T. Turner, 4 A. B. Chapman, 5
J. G. Gums, 1 K. R. Bailey, 4 E. Boerwinkle, 2 J. A. Johnson 1 ; 1 University
of Florida, Gainesville, FL, 2 University of Texas, Houston, TX,
3 University of Maryland, Baltimore, MD, 4 Mayo Clinic, Rochester,
MN, 5 Emory University, Atlanta, GA. Y. Gong: 1. This research
was sponsored by; Company/Drug; NIH grant U01 GM074492.
C.W. McDonough: None. Z. Wang: None. R.M. Cooper-DeHoff:
1. This research was sponsored by; Company/Drug; NIH grant U01
GM074492, HL084090. T.Y. Langaee: 1. This research was sponsored
by; Company/Drug; NIH grant U01 GM074492. A.L. Beitelshee:
1. This research was sponsored by; Company/Drug; NIH grant
U01 GM074492. S.T. Turner: 1. This research was sponsored by;
Company/Drug; NIH grant U01 GM074492. A.B. Chapman: 1.
This research was sponsored by; Company/Drug; NIH grant U01
GM074492. J.G. Gums: 1. This research was sponsored by; Company/Drug;
NIH grant U01 GM074492. K.R. Bailey: 1. This research
was sponsored by; Company/Drug; NIH grant U01 GM074492. E.
Boerwinkle: 1. This research was sponsored by; Company/Drug; NIH
grant U01 GM074492. J.A. Johnson: 1. This research was sponsored
by; Company/Drug; NIH grant U01 GM074492. 2. I am a paid consultant/employee
for; Company/Drug; Medco.
BACKGROUND: To date, 39 SNPs are associated with blood pressure
(BP) in genome-wide association studies (GWAS) in whites. We
assessed the association of these loci with BP response to atenolol
(ATEN) and hydrochlorothiazide (HCTZ), with particular interest in
loci with opposite associations for the two drugs, given their contrasting
pharmacological mechanisms.
METHODS: PEAR evaluated BP response in 768 hypertensive
patients randomized to either ATEN or HCTZ monotherapy then the
combination. Genotypes of 37 loci were obtained from Illumina 50K
cardiovascular or Omni1M GWAS chips. Associations with systolic
(SBP) and diastolic BP (DBP) responses to ATEN or HCTZ mono-
or add-on therapy was evaluated in 464 white individuals using linear
regression adjusting for baseline BP, age, gender and principal components
for ancestry.
RESULTS: Eight SNPs reached nominal significance (p