Genetic variants

The milk of Western cattle contains only a-la B but Zebu and Droughtmas-ter cattle secrete two variants, A and B. a-La A contains no arginine, the one Arg residue of a-la B being replaced by glutamic acid. 

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ECE isoforms are also involved in the degradation of A 3 peptide. A genetic variant of ECE-1 with an increased transcriptional activity is associated with a decreased risk for AD. Thus, the inhibition of ECE in the CNS may increase the risk for the development of Alzheimer s disease (AD). 

DEAE 25W were operated in tandem to map the peptides generated on tryptic hydrolysis of very large proteins, such as albumin genetic variants.197 A useful review that covers many aspects of peptide analysis is available.198... 

Takahashi, N., Takahashi, Y., Ishioka, N., Blumberg, B., and Putnam, F. W., Application of an automated tandem high-performance liquid chromatographic system to peptide mapping of genetic variants of human serum albumin, J. Chromatogr., 359, 181, 1986. 

Ball, S.E. et al. (1999). Population distribution and effects on drug metabolism of a genetic variant in the 5 promoter region of CYP3A4. Clin. Pharmacol. Ther., 66, 288-94. 

The importance of adenosine deaminase in the duration and intensity of sleep in humans has been noted recently (Retey et al. 2005). Animal studies suggest that sleep needs are genetically controlled, and this also seems to apply in humans. Probably, a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and slow wave activity during sleep. Thus low activity of the catabolic enzyme for adenosine results in elevated adenosine, and deep sleep. In contrast, insomnia patients could have a distinct polymorphism of more active adenosine deaminase resulting in less adenosine accumulation, insomnia, and a low threshold for anxiety. This could also explain interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers. This could affect the EEG during sleep and wakefulness in a non-state-specific manner. 

Bowles, J., Blair, D. and McManus, D.P. (1992) Genetic variants within the genus Echinococcus identified by mitochondrial DNA sequencing. Molecular and Biochemical Parasitology 54, 165-174. 

Kragh-Hansen U, Brennan SO, Galliano M, Sugita O. Binding of warfarin, salicylate, and diazepam to genetic variants of human semm albumin with known mutations. Mol Pharmacol 1990 37[2] 238—242. 

Herve F, Gomas E, Duche JC, Tille-ment JP. Evidence for differences in the binding of drugs to the two main genetic variants of human alpha 1-acid glycopro-... 

While many pharmacogenomic mechanisms are possible, genetic variants may alter response to drugs in three main ways (Table 10.1) [31] ... 

Genetic variants associated with altered uptake, distribution or metabolism of the agent administered (Pharmacokinetic)... 

Genetic variants resulting in an unintended action of a drug outside of its therapeutic indication (Idiosyncratic)... 

Beige J, Zilch O, Hohenbleicher H, Ringel J, Kunz R, Distler A, Sharma AM. Genetic variants of the renin-angiotensin system and ambulatory blood pressure in essential hypertension. J Hypertens 1997 15 503-508. 

Rebbeck TR, Jaffe JM, Walker AH, Wein AJ, Malkowicz SB. Modification of clinical presentation of prostate tumours by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1998 90 1225-1229. 

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