Pharmacogenetics and genomics
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Pharmacogenet. Genomics · Nov 2011
Beta2-adrenergic receptor polymorphisms as a determinant of preferential bronchodilator responses to β2-agonist and anticholinergic agents in Japanese patients with chronic obstructive pulmonary disease.
Previous studies have shown that polymorphisms in the β2-adrenergic receptor gene (ADRB2) may influence bronchodilator response (BDR) to both β2-agonists and anticholinergics, possibly by intracellular cross-talk, but in opposite ways, in the Japanese population. We hypothesized that the preferential response to either class of bronchodilators might be determined by ADRB2 polymorphisms in patients with chronic obstructive pulmonary disease (COPD). ⋯ ADRB2 polymorphism may be a determinant of preferential BDR to either β2-agonists or anticholinergics in patients with COPD.
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Pharmacogenet. Genomics · Jun 2010
GSNO reductase and beta2-adrenergic receptor gene-gene interaction: bronchodilator responsiveness to albuterol.
Short-acting inhaled beta2-agonists such as albuterol are used for bronchodilation and are the mainstay of asthma treatment worldwide. There is significant variation in bronchodilator responsiveness to albuterol not only between individuals but also across racial/ethnic groups. The beta2-adrenergic receptor (beta2AR) is the target for beta2-agonist drugs. The enzyme, S-nitrosoglutathione reductase (GSNOR), which regulates levels of the endogenous bronchodilator S-nitrosoglutathione, has been shown to modulate the response to beta2-agonists. ⋯ Genotyping of GSNOR and beta2AR genes may be useful in identifying Latino individuals, who might benefit from adjuvant therapy for refractory asthma.
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Pharmacogenet. Genomics · May 2010
A KCNJ6 (Kir3.2, GIRK2) gene polymorphism modulates opioid effects on analgesia and addiction but not on pupil size.
KCNJ6 coding for potassium inwardly rectifying channels (Kir3.2, GIRK2) is important for opioid receptor transmission. The KCNJ6 rs2070995 AA genotype has been associated with increased opioid analgesic requirements in Japanese. We analyzed its consequences for other opioid effects. ⋯ The association of the KCNJ6 rs2070995 AA genotype with increased opioid requirements extends from analgesia to opiate substitution therapy. Opioid induced miosis is exempted for molecular histological reasons.
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Pharmacogenet. Genomics · Apr 2010
Randomized Controlled Trial Clinical TrialEffect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study.
Three common haplotypes in the gene encoding catechol-O-methyltransferase (COMT) have been associated with pain modulation and the risk of developing chronic musculoskeletal pain, namely temporomandibular disorder (TMD). Haplotypes coding for higher enzymatic activity were correlated with lower pain perception. Rodent studies showed that COMT inhibition increases pain sensitivity through beta2/3-adrenergic receptors. We hypothesized that the nonselective beta-adrenergic antagonist propranolol will reduce clinical and experimental pain in TMD patients in a manner dependent on the individuals' COMT diplotype. ⋯ COMT haplotypes may serve as genetic predictors of propranolol treatment outcome, identifying a subgroup of TMD patients who will benefit from propranolol therapy.
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Pharmacogenet. Genomics · Feb 2010
Development of a Pharmacogenetic Predictive Test in asthma: proof of concept.
To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR). ⋯ Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators.