T polymorphism

Andersen, G., Overgaard, J., Albrechtsen, A., et al. (2006) Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes. Diabetologia. 49, 75-82. 

Strobel, A., Lesch, K. P., Hohenberger, K., et al. (2002) No association between dopamine receptor gene exon III and -521C/T polymorphism and novelty seeking. Mol. Psychiatry. 7, 537-538. 

Elhngrod, V. L., Miller, D., Ringold, J. C., and Perry, P. J. (2004) Distribution of the serotonin 2C (5HT2C) receptor gene -759C/T polymorphism in patients with schizophrenia and normal controls. Psychiatr. Genet. 14,93-95. 

Another widely studied apo A-IV SNP is an A—>T polymorphism at nucleotide 2346 (first base of codon 347), which causes a threonine-to-serine substitution in the protein product.54-55 The A—>T variant at codon 347 occurs at almost double the frequency of the 360G—>T variant with a prevalence of 22% in Caucasian populations.55-56 However, ethnic differences have been described with lower frequencies in African blacks (9.5%) and Hispanic populations (12.9%).53 The 360G— T and 347A—>T genetic variants are in strong linkage disequilibrium and tend not to occur together.55-57... 

CBS deficiency is inherited as an autosomal recessive trait. Homozygous individuals (I in 200,000 births) have classical homocystinuria with extremely high plasma tHcy. The 677 C > T polymorphism in MTHFR is believed to be one of the most common causes of mildly elevated plasma tHcy, The frequency of the homozygous genotype is I 1% to 15% in North Americans, 5% to 23% in Europeans, I I % in healthy Japanese populations, and only 2,5% in the Indian population in New Delhi (12-14). The polymorphism induces thermolability in the enzyme, resulting in defect remethylation of... 

Many studies published during the last few decades have suggested that hyperhomocysteinemia is a risk factor for coronary artery disease (CAD), stroke, and thromboembolic disease. The Homocysteine Studies Collaboration metaanalysis of 30 studies concluded that elevated tHcy is a moderate risk factor for ischemic heart disease a level 3 xmol/L lower reduces the risk with an odds ratio of 0.89 (95% Cl = 0.83-0.96). The same was true for homocysteine as a risk factor for stroke (odds ratio = 0.81 95%5CI = 0.69-0.95) (6). A meta-analysis of 40 studies of the MTHFR 677 C > T polymorphism demonstrated a mildly increased risk of coronary heart disease with an odds ratio of 1. 16 (95% Cl = 1.05-1.28) (25). 

Klerk M, et al. MTHFR 677C- > T polymorphism and risk of coronary heart disease a meta-analysis. JAMA 2002 288(16) 2023-203 I. 

Yokoi T, Sawada M, Kamataki T. Polymorphic drug metabolism studies with recombinant Chinese hamster cells and analyses in human populations. Pharmacogenetics 1995 5 S65-S69. 

But especially since a predicted phenotype based on genotyping data was used to define the study-groups, this investigation cannot consider all the extrinsic and intrinsic factors influencing the real activity of enzymes and transporters. During the further clinical development additional (population) analyses and studies might be required to elucidate the respective influence of the DME+T polymorphism and its consequences further. 

The design of study described here is relatively simple, but nevertheless provides explorative profiling of issues related to DME+T polymorphism, and the same principle could be applied to address further influencing factors or populations. The more complicated part is to define clearly both relatively small test and control groups based on the DME+T properties or other characteristics. 

The role of the -759C/T polymorphism in the 5HT2c receptor gene, located at q24 of the X chromosome, in weight gain from olanzapine has been examined in 42 subjects (age data not provided 34 men) with schizophrenia who took olanzapine 7.5-20 mg/day for 4 weeks (mean endpoint serum concentration 24 ng/ml) (247). There was no difference in mean olanzapine dose between patients with the alleles T or C. Of the 42 patients, 15 gained more than 10% of their body weight and there were no T alleles in those subjects of the other... 

Ronai Z, Szekely A, Nemoda Z et al (2001) Association between novelty seeking and the-521 C/T polymorphism in the promoter region of the DRD4 gene. Mol Psychiatry 6 35-38... 

Distribution of the serotonin 2C (5HT2C) receptor gene -759C/T polymorphism in patients with schizophrenia and normal controls. Psychiatr Genet 14 93-95... 

Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism. Am J Med Genet 133B 97-100... 

More studies have yielded inconsistent results. Three studies demonstrated an effect of the 677C>T polymorphism on MTX efficacy. However, results from these studies were conflicting with the T allele being a marker of both decreased and increased MTX efficacy in US [40] and Polish [41] cohorts respectively and the C allele a marker of increased MTX efficacy in a Dutch cohort [42], Eight studies showed an effect of the T allele on MTX toxicity. Four of these studies examined Asian patients which included Japanese [39,43], Korean [44], and Chinese [45] others included Dutch [37], US [46, 47], and Spanish [48] cohorts. Two metaanalyses have also yielded disparate results. One meta-analysis found an association between the 677C>T polymorphism and MTX toxicity, but no such association for the 1298A>C variant [49], However, another meta-analysis (which included 1,514 patients with RA) found no association between either of these polymorphisms and MTX toxicity and efficacy [50]. 

Hubacek JA, Rothe G, Pit ha J, et al. (1999) C(-260)->T polymorphism in the promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction. Circulation 99 3218—3220... 

KurlandL, Melhus H, Karlsson J, et al. Aldosterone synthase (CYPl 1B2) —344 C/T polymorphism is related to antihypertensive response Result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Am J Hypertens 2002 15 389-393. 

Salonen, J.T., Malin, R., Tuomainen, T.-P, Nyyssonen, K., Lakka, T.A., and Lehtimaki, T., Polymorphism in high density lipoprotein paraoxonase gene and risk of acute myocardial infarction in men prospective nested case-control study, Brit. Med. J., 319,487-489,1999. 

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