BACKGROUND: @entity2067 antagonists are effective in the prevention and treatment of @entity1031 . @entity1229 is one of the most widely prescribed @entity2067 antagonists in the world [1, 2]. It has a narrow therapeutic range and a given dose may result in a large inter-individual variation of response. Insufficient dose may fail to prevent @entity1031 , while an @entity1445 increases the risk of @entity548 . @entity1 -specific factors (e.g., age, body size, race, concurrent diseases, and medications) explain some of the variability in @entity1229 dosage, but genetic factors influencing @entity1229 response explain a significantly higher proportion of this variability [3]. Molecular analysis of the gene that encodes the target enzyme @entity16816 reductase complex 1 ( @entity5058 ) strongly suggests that its genetic variations greatly affect the individual response to oral anticoagulants [4-7]. OBJECTIVE: To evaluate effects of @entity5058 polymorphisms on @entity1229 dose excess anticoagulation (INR >4.0) in the population of Sakha (S) @entity1 . METHODS: 53 @entity1 (29- @entity1 , 24- @entity1 ) with @entity955 (68%), @entity712 (60%), @entity101 (49%) and @entity299 (26%) were recruited. The age range was 26-80 years, with a mean age of 62.87    12.57 years.International normalized ratio and plasma @entity1229 concentrations were determined. Genotyping was carried out by RT-PCR (real-time PCR). The three genetic polymorphisms of the gene @entity5058 @entity69638 ( @entity43397 ) were studied: normal (GG), heterozygous (GA) and homozygous ( @entity5066 ). Fisher exact probability test and chi-square test (with Yates correction) were applied to compare data among the @entity5066 and GG + GA groups; also Mann-Whitney test was used. RESULTS: The median maintenance daily dose of @entity1229 among @entity5066 carriers was 3.0 mg/day [1.25-7.5 mg], while in GG and GA @entity1 it was 3.13 mg/day [1.88-7.92 mg]. The mean daily @entity1229 dosage was higher in GG and GA genotype carriers 4.05 mg/day (SD    1.7) than in @entity1 with @entity5066 genotype 3.13 (SD    1.5). Differences are of borderline significance (p = 0.054). Of the 41 @entity1 who required @entity1229 doses of less than 5 mg, 28 (63%) were found to be @entity5066 carriers and 14 (37%) were GG, GA carriers. Differences were not quite significant (p = 0.072). Among 31 homozygous polymorphism carriers 2 (4%) @entity1 developed overanticoagulation (INR >4.0), while among 22 normal and heterozygous polymorphisms carriers only 3 (6%) @entity1 developed overanticoagulation (INR >4.0). Differences were not statistically significant (p = 0.36). CONCLUSIONS: No significant association between @entity5058 polymorphisms and the frequency of excess anticoagulation (INR >4.0) was found. This may be explained by the number of cases included. @entity5066 polymorphisms compared to other polymorphisms shows borderline difference in the @entity1229 dose. The results can be used for the development of a pharmacogenetic-guided @entity1229 dosing algorithm.

XXXX polymorphisms and @entity1229 maintenance dose in population of Sakha (Yakuts).

@entity1 :: ('9606', 'Species') :: ['men', 'women', 'Patient', 'patients'] @entity712 :: ('MESH:D006333', 'Disease') :: ['congestive heart failure'] @entity43397 :: ('rs9923231', 'SNP') :: ['rs9923231'] @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension'] @entity548 :: ('MESH:D006470', 'Disease') :: ['bleeding'] @entity2067 :: ('MESH:D014812', 'Chemical') :: ['vitamin K', 'Vitamin K'] @entity5058 :: ('79001', 'Gene') :: ['VKORC1'] @entity5066 :: ('MESH:C566236', 'Disease') :: ['AA'] @entity69638 :: ('g|SUB|G|3673|A', 'DNAMutation') :: ['G3673A'] @entity1031 :: ('MESH:D013923', 'Disease') :: ['thromboembolic disorders', 'thromboembolism'] @entity955 :: ('MESH:D001281', 'Disease') :: ['atrial fibrillation'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac valve replacement'] @entity16816 :: ('MESH:C016186', 'Chemical') :: ['vitamin K epoxide'] @entity1445 :: ('MESH:D062787', 'Disease') :: ['overdose'] @entity1229 :: ('MESH:D014859', 'Chemical') :: ['warfarin', 'Warfarin']
@entity5058 :: (79001,Gene) :: ['VKORC1']
