Pharmacogenetics and genomics
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Pharmacogenet. Genomics · Jun 2009
Multicenter Study Clinical TrialCross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers.
A finite number of variants in the OPRM1, COMT, MC1R, ABCB1 and CYP2D6 genes has been identified to significantly modulate the effects of opioids in controlled homogenous settings. We analyzed the imprint of these variants in opioid therapy in a highly variable cohort of pain patients treated in outpatient units to test whether genotyping may play a role in this clinical setting. ⋯ Genetics were reflected in the outpatient pain therapy only to a modest degree. The need of outpatient therapy of pain of various causes guided by the presently known functional genetic variants cannot be convincingly concluded from the present data. Using the ABCB1 3435 genotype to predefine lower individual opioid doses barely merits the laboratory effort. If any, the results suggest that a genetics guided outpatient pain therapy may be based on ABCB1 and OPRM1 variants.
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Pharmacogenet. Genomics · May 2009
A common gene variant in methionine synthase reductase is not associated with peak homocysteine concentrations after nitrous oxide anesthesia.
Oxidation of vitamin B12 by nitrous oxide leads to the inactivation of methionine synthase resulting in elevated plasma total homocysteine concentrations. Methionine synthase reductase is the only human enzyme that is able to reverse the oxidation of vitamin B12, which also occurs naturally by reactive oxygen species. A common polymorphism in methionine synthase reductase, MTRR 66A>G, is associated with reduced enzyme activity. Thus, we hypothesized that patients with this gene variant develop higher plasma total homocysteine concentrations after nitrous oxide anesthesia than wild-type patients. ⋯ In conclusion, this study showed that the MTRR 66A>G gene variant is not associated with peak elevated postoperative plasma total homocysteine after nitrous oxide anesthesia. Whether the gene influences the rate of recovery of methionine synthase remains to be determined.
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Pharmacogenet. Genomics · Jan 2009
The effect of catechol-O-methyltransferase Met/Val functional polymorphism on smoking cessation: retrospective and prospective analyses in a cohort study.
The Met/Val functional polymorphism of the gene-encoding catechol-O-methyltransferase (COMT) is one of the most widely tested variants for association with different phenotypes of addictive behavior, but replication has been inconsistent for smoking status. We investigated the relationship of this COMT single nucleotide polymorphism with smoking cessation in elderly persons in retrospective and prospective analyses. ⋯ Our results suggest that COMT Met/Val polymorphism is strongly associated with smoking cessation. The Met allele is the risk allele that decreases the likelihood of smoking cessation in men and women.
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Pharmacogenet. Genomics · Dec 2008
A paucimorphic variant in the HMG-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study.
Considerable interindividual variation exists in cholesterol-lowering response to 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors (statins). HMGCR catalyzes the rate-limiting step in cholesterol biosynthesis, and also plays a significant role in cholesterol homeostasis. We evaluated the association of a single nucleotide polymorphism (rs17238540) in the HMGCR gene with lipid-lowering response to statins in a large population-based cohort of patients with diabetes. ⋯ Individuals heterozygous for the G allele of rs17238540 in the HMGCR gene may respond less well to statin therapy in terms of total cholesterol and triglyceride lowering.