ABSTRACT
BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.
Subject(s)
Arrhythmias, Cardiac/genetics , Black or African American/genetics , Connexin 43/genetics , Genetic Variation , Genome-Wide Association Study/methods , Heart Rate , Rest/physiology , Adult , Aged , Arrhythmias, Cardiac/ethnology , Arrhythmias, Cardiac/physiopathology , Connexin 43/metabolism , Electrocardiography , Female , Genotype , Humans , Male , Meta-Analysis as Topic , Middle Aged , Polymorphism, Single Nucleotide , United States/epidemiologyABSTRACT
A fall in systolic blood pressure without other symptoms of anaphylactic shock has been described following the administration of drugs containing dipyrone. This adverse reaction was first observed in 4 patients by the same team in 1972-1973. Ten further cases with a fall in systolic blood pressure by at least 20 mm Hg occurring within minutes to 6 hours after intravenous administration of dipyrone are presented in this paper. In each of them this adverse reaction was considered to be probable or even definite. During the years 1976-1981 drug exposure was registered for all 15 678 patients of the two medical divisions of Comprehensive Hospital Drug Monitoring Berne. This adverse reaction was found in 7, representing 0.34% of the 2053 patients who received intravenous treatment with a dipyrone preparation.
Subject(s)
Aminopyrine/analogs & derivatives , Blood Pressure/drug effects , Dipyrone/adverse effects , Aged , Female , Humans , Male , Middle Aged , Systole , Time FactorsABSTRACT
Longterm therapy of chronic bacterial bronchitis assumes two forms: (a) therapy of acute exacerbations, and (b) continuous longterm prophylaxis, chiefly during the 4-7 winter months. Longterm prophylaxis should be confined exclusively to patients with two or more severe annual exacerbations. The commonest pathogens, Haemophilus influenzae and pneumococci, are usually sensitive to ampicillin and amoxycillin, cotrimoxazole (Bactrim or Eusaprim) and tetracyclines.
