Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the therapeutic dose. Complications from inappropriate warfarin dosing are one of the most common reasons for emergency room visits. Approximately one third of warfarin dose variability results from common genetic variants. Therefore, it is very necessary to recognize warfarin sensitivity in individuals caused by genetic variants. Based on combined polymorphisms in CYP2C9 and VKORC1 , we established a clinical classification for warfarin sensitivity. In the International Warfarin Pharmacogenetic Consortium (IWPC) with 5542 patients, we found that 95.1% of the Black in the IWPC cohort were normal warfarin responders, while 74.8% of the Asian were warfarin sensitive (P < 0.001). Moreover, we created a clinical algorithm to predict warfarin sensitivity in individual patients using logistic regression. Compared to a fixed-dose approach, the clinical algorithm provided significantly better performance. In addition, we validated the derived clinical algorithm using the external Easton cohort with 106 chronic warfarin users. The AUC was 0.836 vs. 0.867 for the Easton cohort and the IWPC cohort, respectively. With the use of this algorithm, it is very likely to facilitate patient care regarding warfarin therapy, thereby improving clinical outcomes.

Background: Clopidogrel (Plavix) is an antiplatelet medication that is routinely used in patients with cardiovascular disease. Cytochrome P2C19 enzymes play a major role in its metabolism, which determines its varied therapeutic level and its effectiveness.Objectives: To customize clopidogrel therapy and evaluate its efficacy by using CYP2C19 genotypic and phenotypic information to improve clinical outcomes in patients.Methods: A total of 465 patients with underlying cardiovascular disease were selected from our out-patient cardiology clinic. DNA sequences of CYP2C19 were analyzed in 465 patients.Results: Of 465 patients, 183 were wild-type homozygous (*1/*1) and 18.8% gain-of function and 19.8% loss-of-function alleles in our patient population The following changes were made: 1) Switching to prasugrel in patients whose genotype noted them to be “Slow metabolizers. This medication adjustment improved clinical outcomes in this patient group.2) Discontinuing or lowering clopidogrel doses in patients whose genotypes noted them to be “Fast or ultra-fast metabolizes” to decrease bleeding risk. For those who were not on clopidogrel but carried abnormal allele(s), “clopidogrel caution” was documented. These individuals were followed up for 3 years and there has not been any cardiac clinical symptoms, cardiac death or excessive bleeding reported.Conclusions: Given the varied effectiveness of clopidogrel due to its metabolism by CYP2C19 enzyme, and the relatively high frequency of both gain-of-function (18.8%) and loss-of-function (19.8%) alleles in our patient population, we believe that genotyping CYP2C19 is clinically important in order to improve patient outcomes and minimize patient risk.

This study indicates that MTHFR C677T and MTHFR A1298C gene polymorphisms have opposite effect on systemic inflammation, and systemic inflammation may contribute to the pathogenesis for diseases associated with MTHFR C667T gene polymorphism.

pharmacogeneTic TesTing on Warfarin anD clopiDorgel in conDiTions of a mulTiprofile hospiTal Ketova g. g., Barysheva V. o. south ural state medical university, chelyabinsk, russian federation ФАРмАКОГЕНЕТИЧЕСКОЕ ТЕСТИРОВАНИЕ НА ВАРФАРИН И КЛОпИДОГРЕЛ В УСЛОВИЯХ мНОГОпРОФИЛЬНОГО СТАЦИОНАРА Г. Г. Кетова, В. О. Барышева Южно-Уральский государственный медицинский университет, Челябинск, Российская Федерация In the study 236 patients was included. Decoding of the genotypes was carried out with kits of reagent for determining genetic polymorphisms associated with the metabolism of warfarin or clopidogrel with detection PCR results in real-time; and melting curve analysis, qualitative analysis («NPO DNA-Technology», Russia). The age mean age of the patients was 57.5±12.01 years. Gender differences included 54.6 % male. Clopidogrel sensitivity is influenced by several genetic polymorphisms: АВСВ1: CC-19.1 %, CT-42.6 %, TT-31.2 %.