Pharmacogenomics
-
To determine and compare the cytochrome P450 (CYP)2C9, CYP2C19 and CYP2D6 allele and genotype frequencies in the Ashkenazi Jewish (AJ) population with other populations. ⋯ Although the CYP2C9 allele and genotype frequencies in the AJ subjects were similar to those in other North American Caucasian populations, genotyping the CYP2C19*4 and CYP2D6*41A alleles in the AJ population resulted in the clinically relevant reclassification of the predicted metabolizer phenotypes. Inclusion of CYP2C19*4 reclassified individuals from either extensive- or intermediate- to the intermediate- or poor-metabolizer phenotypes, respectively. Inclusion of the redefined CYP2D6*41A allele increased the ultrarapid-, intermediate- and poor-metabolizer phenotype combined frequencies to 30%, indicating that approximately one in three AJ individuals may benefit from genotype-based drug selection and dosage. In addition, the ultrarapid CYP2D6 genotype frequency in the AJ population (8.8%) was approximately twofold higher than that in other North American Caucasians.
-
Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. ⋯ The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS.
-
Genetic variation contributes to an individual's sensitivity and response to a variety of drugs important to anesthetic practice. Early insights into the clinical impact of pharmacogenetics were provided by anesthesiology--investigations into prolonged apnea after succinylcholine administration, thiopental-induced porphyria and malignant hyperthermia contributed to the novel science of pharmacogenetics in the early 1960s. ⋯ In addition, genetic variation in proteins directly unrelated to drug action or metabolism can influence responses to environmental changes that occur during anesthesia. This review will summarize the current knowledge of genetic variation in response to drugs relevant to anesthesia, and how this impacts upon clinical practice.
-
The beta(2)-adrenergic receptor (beta(2)AR or ADRbeta(2)) is the target for beta(2)-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The aim of this study was to identify common single nucleotide polymorphisms (SNPs) and haplotypes in asthmatics and healthy individuals from an Indian population, and determine the influence of beta(2)AR SNPs in responsiveness to beta(2)-agonist therapy in asthma patients. ⋯ This study suggests that the SNP at nucleotide position 46 has particular relevance to pharmacogenetics in the Indian population studied.