PubMed Health⌕ Search

Biomedical subjects

David E Lanfear

Publications and source records attributed to David E Lanfear.

4 recordsLinked to original sources
PubMed2005

Beta2-adrenergic receptor genotype and survival among patients receiving beta-blocker therapy after an acute coronary syndrome.

CONTEXT: Previous data support an association between polymorphisms of the beta1- and beta2-adrenergic receptors (ADRB1 and ADRB2) and surrogate end points of response to beta-adrenergic blocker therapy. However, no associations between these polymorphisms and mortality have been demonstrated. OBJECTIVE: To evaluate the effect of ADRB1 Arg389Gly (1165 CG), Ser49Gly (145 AG), and ADRB2 Gly16Arg (46 GA), Gln27Glu (79 CG) genotypes on survival among patients discharged with prescribed beta-blockers after an acute coronary syndrome (ACS). DESIGN, SETTING, AND PATIENTS: Prospective cohort study of 735 ACS patients admitted to 2 Kansas City, Mo, medical centers between March 2001 and October 2002; 597 patients were discharged with beta-blocker therapy. MAIN OUTCOME MEASURE: Multivariable-adjusted time to all-cause 3-year mortality. RESULTS: There were 84 deaths during follow-up. There was a significant association between ADRB2 genotype and 3-year mortality among patients prescribed beta-blocker therapy. For the 79 CG polymorphism, Kaplan-Meier 3-year mortality rates were 16% (35 deaths), 11% (27 deaths), and 6% (4 deaths) for the CC, CG, and GG genotypes, respectively (P = .03; adjusted hazard ratios [AHRs], 0.51 [95% confidence interval {CI}, 0.30-0.87] for CG vs CC and 0.24 (95% CI, 0.09-0.68) for GG vs CC, P = .004). For the ADRB2 46 GA polymorphism, 3-year Kaplan-Meier mortality estimates were 10% (17 deaths), 10% (28 deaths), and 20% (20 deaths) for the GG, GA, and AA genotypes, respectively (P = .005; AHRs, 0.48 [95% CI, 0.27-0.86] for GA vs AA and 0.44 [95% CI, 0.22-0.85] for GG vs AA, P = .02). No mortality difference between genotypes was found among patients not discharged with beta-blocker therapy for either the 79 CG or 46 GA polymorphisms (P = .98 and P = .49, respectively). The ADRB2 diplotype and compound genotypes were predictive of survival in patients treated with beta-blockers (P = .04 and P = .002; AHRs, 5.36 [95% CI, 1.83-15.69] and 2.41 [95% CI, 0.86-6.74] for 46 A homozygous and composite heterozygous vs 79 G homozygous, respectively). No association of the ADRB1 variants with mortality was observed in either the beta-blocker or no beta-blocker groups. CONCLUSIONS: Patients prescribed beta-blocker therapy after an ACS have differential survival associated with their ADRB2 genotypes. Further assessment of the benefits of beta-blocker therapy in high-risk genotype groups may be warranted.

Adrenergic beta-Antagonists↗
PubMed2004

Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans.

OBJECTIVES: This study was designed to describe the frequencies of multiple myocardial infarction (MI) risk-associated genotypes among different racial groups. BACKGROUND: Racial disparities in the prevalence of cardiovascular disease (CVD) are well known. Recent large Japanese case-control studies identified connexin-37 (GJA-4), plasminogen activator inhibitor-1 (PAI-1), and stromelysin-1 (MMP-3) polymorphisms as risk factors for MI, but the prevalence of these genotypes among different racial groups in the U.S. needs to be determined. METHODS: Genomic deoxyribonucleic acid from 95 healthy African Americans (AA) and 95 healthy European Americans (EA) was used for genotyping. Deoxyribonucleic acid containing the region of interest was amplified using the polymerase chain reaction, followed by genotyping using pyrosequencing. RESULTS: All three MI-risk genotypes were observed in both populations and were in Hardy-Weinberg equilibrium. The frequencies of two of the three "risk-associated" genotypes were significantly higher in the AA population: GJA4 C1019T T/T: AA, 20%, EA, 7% (p = 0.053); MMP3 -1171delA A/A: AA, 78%, EA, 24% (p < 0.001); PAI-1 -668delG G/G: AA, 55%, EA, 16% (p < 0.001). The likelihood of two or more high-risk genotypes was 3.3% among EA subjects and 51% in the AA group (p < 0.001). We found that 9.1% of AA had all three high-risk genotypes, compared with 0% among the EA group (p = 0.0097). CONCLUSIONS: We found higher frequencies of disease-associated genotypes in AA than in EA. Our results also show that more AA than EA carry multiple risk-associated genotypes. Future studies need to assess whether such genetic profiles predict adverse outcomes in U.S. populations and contribute to racial disparities in CVD burden.

Black or African American↗
PubMed2004

Frequency of compound genotypes associated with beta-blocker efficacy in congestive heart failure.

An important practical problem in pharmacogenetics is the integration of compound genotypes into individualized therapy. Polymorphisms in the genes encoding the angiotensin-converting enzyme, and beta(1)- and beta(2)-adrenoceptors have been identified as predictors of 'good response' to beta-adrenergic antagonists among heart failure patients. These variants were used as the basis for exploring the concept of compound genotype assessment. The frequency of compound variants in these genes was determined using PCR and pyrosequencing to genotype population samples of 95 African-Americans and 95 European-Americans. Both groups could be divided into four subgroups according to the number of favorable genotypes present. Each subgroup accounted for a significant proportion of subjects (the smallest was 7% of total). This study provides the first look into the population frequency of these compound genotypes, and it provides the necessary first step for future evaluation of polygenic strategies to individualize therapy for heart failure.

Adrenergic beta-Antagonists↗