A. Sloan

University of Florida, Gainesville, Florida, United States

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Publications (4)27.38 Total impact

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    ABSTRACT: Purpose: Polymorphisms (SNPs) of the B2AR gene have been associated with hypertension. We investigated the association of several B2AR SNPs and blood pressure (BP) responses to atenolol.Methods: Data and genomic samples were obtained from 740 participants of the International Verapamil-Trandolapril Study (INVEST) trial with hypertension and coronary artery disease in whom atenolol was added as monotherapy or was added to stable background therapy. Arg16Gly, Gln27Glu and a synonymous CA SNP at nt523 were genotyped by pyrosequencing. Analysis of covariance was used to compare BP responses to atenolol at 6 weeks among genotypes adjusting for age (66.2 9.2), BMI, baseline BP and race.Results: Minor allele frequencies for Arg16Gly, Gln27Glu and nt523 C to A were 0.42, 0.34 and 0.28, respectively. Codon 16 polymorphisms were not associated with BP response to atenolol. 27Gln and nt523A alleles of B2AR were associated with significantly better systolic blood pressure (SBP) response to atenolol (p= 0.0080 and p= 0.0288). 27Gln carriers also showed better diastolic blood pressure (DBP) response (p= 0.0242) to atenolol therapy. (see Table)Conclusion: Our data suggest that codon 27 and nt523 gene variants may be important determinants of variable BP response to atenolol therapy in older hypertensives with coronary disease.
    Clinical Pharmacology &#38 Therapeutics 01/2005; 77(2):P22-P22. · 6.85 Impact Factor
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    ABSTRACT: Traditional risk factors have been linked to heart failure (HF) severity. We investigated whether |[beta]|1-adrenergic receptor (AR) genotypes and variable HF drug use offer additional prognostic information.Patients with documented HF were enrolled and followed for all-cause mortality, heart transplant, or HF hospitalization. Cox regression was used to examine the effects of covariates on outcome. Variables included traditional demographic, medical and social history, and laboratory parameters along with use of digoxin and spironolactone, |[beta]|1AR codon 49 genotype, and |[beta]|1AR codon 389 genotype. |[beta]|-blocker, ACE inhibitor, and diuretic use were high at baseline and end of follow-up and not included in the model. Significance for inclusion in the model was set at 0.1.Patients (n=181) were followed for a median of 18 months (4 days min, 36 months max). Significant markers of HF prognosis are presented (Table). HF drugs with variable use (digoxin, spironolactone) and |[beta]|1AR genotypes were not significant.Traditional risk factors associated with worse HF prognosis were verified in our population. |[beta]|1AR genotypes and digoxin and spironolactone use were not associated with the composite endpoint. The guideline-driven high use of |[beta]|-blockers in this population may have masked any |[beta]|1AR genotype effects on endpoints.
    Clinical Pharmacology &#38 Therapeutics 01/2004; 75(2):P55-P55. · 6.85 Impact Factor
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    ABSTRACT: Purpose: The CYP3A5 |[ast]|3, |[ast]|6, and |[ast]|7 alleles have a greatly reduced capacity to produce functional CYP3A5 enzyme relative to the |[ast]|1 allele. Polymorphic renal CYP3A5 expression may regulate blood pressure (BP) and risk of hypertension (HTN). A previous study of 25 young healthy African-Americans (AA) showed an association between CYP3A5 genotype and BP.Methods: A total of 564 AAs (n=266) and Caucasians (n=298) normotensives (NT) with no known family history of HTN and hypertensives (HT) with a family history of HTN were genotyped for CYP3A5 |[ast]|3 (and |[ast]|6 and |[ast]|7 in AAs only) using pyrosequencing technology. CYP3A5 haplotypes for AAs were determined by computational methods. Functional allele status was determined based on |[ast]|3 genotype for Caucasians (ie: |[ast]|1,|[ast]|3=1 functional allele) and |[ast]|3, |[ast]|6 and |[ast]|7 diplotype for AAs (ie: |[ast]|1, |[ast]|1, |[ast]|1/,|[ast]|1, |[ast]|6, |[ast]|1=1 functional allele).Results: There were no differences in functional allele/haplotype frequencies between HT (0.16) and NT Caucasians (0.11); p=0.21, or HT (0.60) and NT AAs (0.56); p=0.52. There were also no differences in BP (Mean |[plusmn]| SD) by number of functional alleles among NT AAs or Caucasians (Table).Conclusion: There was no association between hypertension or BP and CYP3A5 expressor (|[ast]|1) versus nonexpressor (|[ast]|3, |[ast]|6, |[ast]|7) alleles in AAs or Caucasians.
    Clinical Pharmacology &#38 Therapeutics 01/2004; 75(2):P13-P13. · 6.85 Impact Factor
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    ABSTRACT: The |[beta]|2AR gene has been associated with hypertension, but data are conflicting. Racial differences in this association or role of the |[beta]|2AR haplotype have not been well studied. We sought to determine whether race and/or haplotype influence the association between the |[beta]|2AR gene and hypertension. Genetic samples were obtained from African American (AA) or Caucasian (C) hypertensive (HT) or normotensive (NT) patients. |[beta]|2AR codon 16 and 27 genotypes were determined by PCR and luciferase-based pyrosequencing. Differences were analyzed by Chi-square and Fisher's exact test with AA and C analyzed separately. Haplotype frequencies were compared by race between NT and HT. A total of 482 patients were enrolled. Allele and genotype frequencies were similar for HT and NT at codons 16 and 27 for both AA and C. No differences were found in |[beta]|2AR haplotypes between NT and HT for AA or C (Table). There were no differences in blood pressure across haplotype for NT AA or C. Our data do not support a significant contribution of the |[beta]|2AR gene to hypertension risk.
    Clinical Pharmacology &#38 Therapeutics 01/2004; 75(2):P95-P95. · 6.85 Impact Factor