Polymorphisms associations

Similar to 5-FU, there is a polymorphism associated with irinotecan toxicity. UDP-glucuronosyltransferase (UGT1A1) is an enzyme responsible for the glucuronidation of SN-38 to inactive metabolites, and reduced or deficient levels of this enzyme correlate with irinotecan-induced diarrhea and neutropenia.39 Recently the FDA approved a blood test that detects variations in this gene. This test will assist health care providers in predicting which patients may develop severe toxicities from normal doses of irinotecan and can be ordered prior to patients receiving irinotecan. binotecan is administered as an IV bolus over 60 to 90 minutes in a variety dosing schedules. 

Cheong HS, Park CS, Kim LH, et al. CXCR3 polymorphisms associated with risk of asthma. Biochem Biophys Res Commun 2005 334(4) 1219-1225. 

Snutch, T.P. and Baillie, D.L. (1984) A high degree of DNA strain polymorphism associated with the major heat shock gene in Caenorhabditis elegans. Molecular and General Genetics 195, 329—335. 

Thermal methods of analysis were used to study the polymorphism associated with pindolol [29]. The overlapping melting endotherms of the different forms were separated by peak fitting analysis and grouping of materials by the temperature of... 

El-Omar EM et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000 404J6776] 398—402. 

Identification of polymorphisms associated with response and/or side-effects => Individual tailoring based on predictive tests Identification of the biological mechanisms responsible for side-effects. 

Nie L, Niu S, Vega GL, Clark LT, Tang A, Grundy SM, et al. Three polymorphisms associated with low hepatic lipase activity are common in African Americans. J Hpid Res 1998 39 1900-1903. 

The following also points to a dysregulation of the ubiquitin-proteasome pathway as an important aspect of PD pathogenesis rare mutations in ubiquitin car-boxy-terminal hydrogenase LI (UCH-L1) associated with autosomal dominant PD in a German family [120], a UCH-L1 polymorphism associated with the develop-... 

Single-base substitutions, which affect the amino acid sequence of proteins and lead to altered protein function, are the most frequent type of polymorphisms associated with many disease phenotypes as well as with variation in drag response... 

Finally, polymorphisms associated with arylamine N-acetyltransferase (NAT2) may result in slow acetylators. The slow-acetylator phenotype is present in 50-70% of the population in Western countries and is associated with several drug-induced side effects. The frequency of the slow-acetylator phenotype rises to 80% in Egyptian and certain Jewish populations however, the frequency drops to 10% or 20% among Japanese and Canadian Eskimos. 

K. T., Saksena, S., Schwartz, P.J., Priori, S.G., Roden, D.M., George, A.L.J. and Goldstein, S.A. (2000) A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proceedings of the National Academy of Sciences of the United States of America, 97, 10613-10618. 

Cytochromes P450 Genetic Polymorphisms Associated with Nicotine Metabolism... 

Lemon de S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, Sequeira A, KushwahaN, Morris SJ, Basak A, Ou XM, Albert PR (2003) Impaired repression at a 5-hydroxytryptamine lA receptor gene polymorphism associated with major depression and suicide. J Neurosci 23 8788-8799... 

Ebstein, R.P., Novick, O., Umansky, R., Priel, B., Osher, Y., Blaine, D., Bennett, E.R., Nemanov, L., Katz, M., and Belmaker, R.H. (1996) Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nat Genet 12 78-80. 

TS, DPD, MTHFR Polymorphisms Associated with Outcome and Toxicity... 

Wadelius M, Chen LY, Downes K et al. Common VKORCl and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J2005 5. 262-270. 

Ebstein, Richard P., Olga Novick, Roberto Umansky, Beatrice Priel, Yamina Osher, Damen Blaine, Estelle R. Bennett, Lubov Nemanov, Miri Katz, and Robert H. Belmaker. 1996. "Dopamine D4 Receptor (D4DR) Exon III Polymorphism Associated with the Human Personality Trait of Novelty Seeking." Nature Genetics 12 78-80. 

Chiba M, Suzuki S, Hinokio Y, et al. Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder. Metabolism 2000 49 1145-1149. 

Rewers M, Kamboh MI, Hoag S, Shetterly SM, Ferrell RE, Hamman RF. ApoA-TV polymorphism associated with myocardial infarction in obese NIDDM patients. The San Luis Valley Diabetes Study. Diabetes. 1994,43 1485-1489. 

HT Decreased FC 5-HT2A receptor expression Increased FC 5-HT1A receptors Increased 5-HT transporter affinity Developmental and trophic roles of 5-HT 5-HT2 agonists (e.g. LSD) are psychotomimetics 5-HT2 receptor polymorphisms associated with schizophrenia and clozapine response Atypical antipsychotics have high affinity for several 5-HT receptors... 

Macphee I, Fredericks S, Tai T, Syrris P, Carter N, Johnston A, Goldberg L, Holt DW. Tacrolimus pharmacogenetics polymorphisms associated with expression of cytochrome P4503A5 and P-glycoprotein correlate with dose requirement. Transplantation 2002 74 1486-1489. 

Wang J, Near S, Young K, Connelly PW, Hegele RA. ABCC6 gene polymorphisms associated with variation in plasma lipoproteins. J Hum Genet 2001 46 699-705. 

Howard LA, Ahluwalia JS, Lin SK, Sellers EM, Tyndale RF. CYP2E1 1D regulatory polymorphism association with alcohol and nicotine dependence. Pharmacogenetics 2003 13 321-328. 

Table 1 Polymorphisms Associated with Variant Ion Channel Phenotypes...

Sesti F, Abbott GW, Wei J, Murray KT, Saksena S, Schwartz PJ, Priori SG, Roden DM, George AL, Goldstein SA Jr. A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proc Natl Acad Sci USA 2000 97 10613-10618. 

Table 1 Single Nucleotide Polymorphisms Associated to Reduction in Systolic Blood Pressure Upon Antihypertensive Treatment...

Allele-specific differences between regulatory polymorphisms associated with the ability of RNA polymerase II to bind and assemble its transcription complex at the start site of transcription for several eukaryotic promoters has also been measured using MALDI-TOF MS coupled with primer extension (42). This technique provides a powerful tool for identifying important regulatory SNPs and haplotypes in vivo. 

Locus Gene/s/ Gene symbol Size of region Frequency of polymorphism Associated phenotype References... 

Actually, CY2D6 gene polymorphisms, associated with null or reduced enzyme activity, have been reported to negatively influence (in a gene-dose manner) the blood level of endoxifen in numerous prospective pharmacokinetic studies [11,172, 192-196], Some retrospective and prospective studies have shown that CYP2D6 polymorphism was associated with worse clinical outcomes in PMs and IMs patients in terms of recurrence and disease free survival or BC development in the chemo-prevention setting [192,194,195,197-205],... 

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