Polymorphisms impact

Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions a genetic susceptibility mechanism for depression. Nat Neurosci 8 828-834. 

Miners, J. (2002). CYP2C9 polymorphism Impact on tolbutamide pharmacokinetics and response. Pharmacogenetics 12, 91-92. 

Many molecules are obtained and used in a crystalline form, the nature of which can have e significant impact on their properties and behaviour. Moreover, it is sometimes possible foi a given material to exist in more than one crystalline form, depending upon the conditions under which it was prepared. This is the phenomenon of polymorphism. This can be important because the various polymorphs may themselves have different properties. It is Iberefore of interest to be able to predict the three-dimensional atomic structure(s) that a gi en molecule may adopt, for those cases where it is difficult to obtain experimental data and also where one might wish to prioritise molecules not yet synthesised. 

Diamonds also occur in meteorites, probably as a result of high pressures produced dynamically by impact (10,11). The shock or explosive mode of synthesis is a viable process for fine diamond powders of both the cubic and hexagonal (lonsdaleite) polymorphs (12) naturally or otherwise. Some diamonds in space appear to have formed by processes more closely related to the low pressure chemical vapor deposition processes described later (see... 

There are only very few genes which do not carry any polymorphisms. And there exists even a significant number of polymorphic genes that are not expressed at all in part of the population due to genetic polymorphisms. Table 1 summarizes a few selected polymorphisms with their functional and medical impact. 

Pharmacogenetics. Table 1 Selected genetic polymorphisms and their medical impact... 

Enzyme Functional effects of polymorphism and frequency Examples for the medical impact... 

Mountain, J. L., A. A. Lin, A. M. Bowcock, and L. Cavalli-Sforza (1993), Evolution of modern humans Evidence from nuclear DNA polymorphisms, in Aitken, M. J., Stinger, C. B. and P. A. Mellars (eds.), The Origin of Modern Humans and the Impact of Chronometric Dating, Princeton University Press, Princeton, NJ. 

Association studies are used to identify common alleles more frequently associated with phenotypic traits such as drug response or ADRs. These associated alleles are called causal polymorphisms or functional polymorphisms and are risk-conferring factors of the trait at the population level, while, at the individual level, they impact either on the cellular level of the gene product or its function. 

It has now been established that genetic polymorphisms in drug metabolizing enzymes such as the cytochrome P450s (CYP) and the phase II enzyme, thiopu-rine methyltransferase, are responsible for inter-individual variability in response and adverse reactions [12, 13]. However, at the present time, the impact of poly-... 

The combination of GenBank cDNA sequence comparison and data from the public SNP database reveal the presence of several SNPs in MRP3, many of which involve non-synonymous amino acid changes (Table 9.3). These polymorphisms have not been functionally characterized and, therefore, the clinical pharmacological impact of such MRP3 variants remains unknown. 

Mutations within the SREBPs and the SREBP processing proteins (SCAP, SIP, S2P) have intensively been searched, especially in patients with familial hypercholesterolemia. So far, however, only four polymorphic sites within SCAP [38, 39], one within the promoter of SREBP-la [40], and five mutations in SREBP-2 [41] have been published. Yet, the impact of these polymorphisms and mutations on the response to statins has not been evaluated. 

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