Pharmacogenetics and genomics
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Pharmacogenet. Genomics · May 2006
Comparative StudyRestenosis after percutaneous coronary intervention is associated with the angiotensin-II type-1 receptor 1166A/C polymorphism but not with polymorphisms of angiotensin-converting enzyme, angiotensin-II receptor, angiotensinogen or heme oxygenase-1.
The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems. ⋯ We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation.
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Pharmacogenet. Genomics · Feb 2006
Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV. Role of dopaminergic pathway gene polymorphisms.
Tardive dyskinesia (TD) is an antipsychotic induced side effect observed in 20-30% of schizophrenia subjects on long-term typical antipsychotic treatment. We tested the possible association of 24 polymorphisms from six dopaminergic genes: namely, dopamine receptors D1, D2, D3, D4; the dopamine transporter (DAT); and the catalyzing enzyme catechol-O-methyltransferase (COMT), with TD. ⋯ Our study presents a detailed analysis of the possible role of dopaminergic genes in the genesis of TD. DRD4 and COMT genes were observed to be the most important candidates in North Indian schizophrenia subjects. These suggestive associations need to be investigated in replicate studies.
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Pharmacogenet. Genomics · Nov 2005
ADH4 gene variation is associated with alcohol and drug dependence: results from family controlled and population-structured association studies.
We found strong associations between ADH4 gene variation and alcohol and drug dependence by the Hardy-Weinberg Disequilibrium (HWD) test and case-control association analysis in an initial study. The present study aimed to confirm these findings by controlling for population stratification and admixture effects to which the HWD test and case-control association methods may be vulnerable. In addition to 365 unrelated healthy controls and 560 unrelated cases in the initial study, we evaluated 104 small nuclear families with affected offspring who had diagnoses of alcohol and/or drug dependence. ⋯ Logistic regression analysis showed that: (i) the genotypes of SNP2 (rs1042363) were significantly associated with alcohol dependence and drug dependence (mainly cocaine dependence), and the genotypes of SNP3 (rs1126671) were also significantly associated with alcohol dependence and (ii) one seven-variant haplotype and one diplotype were significantly associated with alcohol dependence and other seven-variant diplotypes were significantly associated with drug dependence (including cocaine and opioid dependence). Transmission disequilibrium test, haplotype-based haplotype relative risk and genotype-based haplotype relative risk analyses all confirmed the association of the ADH4 markers with alcohol dependence and drug dependence. Using rigorous study designs that account for possible population stratification, these findings confirm and extend our original observations indicating that variation at ADH4 predisposes to alcohol and drug dependence.
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Pharmacogenet. Genomics · May 2005
Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.
Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes. ⋯ The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.