Influence of VKORC1 and CYP2C9 Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves
| Autor: | S.R. Kalpana, C.N. Manjunath, G. Bharath, Rita Christopher |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Genotype medicine.drug_class medicine.medical_treatment India 030204 cardiovascular system & hematology Pharmacology Polymorphism Single Nucleotide Gastroenterology 03 medical and health sciences 0302 clinical medicine Valve replacement Vitamin K Epoxide Reductases Internal medicine medicine Humans Allele CYP2C9 Cytochrome P-450 CYP2C9 Acenocoumarol business.industry Rheumatic Heart Disease Wild type Hematology General Medicine Vitamin K antagonist Heart Valve Prosthesis 030220 oncology & carcinogenesis Female VKORC1 business medicine.drug |
| Zdroj: | Clinical and Applied Thrombosis/Hemostasis. 23:876-882 |
| ISSN: | 1938-2723 1076-0296 |
| Popis: | Background and Aim: Chronic rheumatic heart disease (RHD) patients who undergo valve replacement with mechanical valves require lifelong anticoagulation. Acenocoumarol, a vitamin K antagonist has a narrow therapeutic range and wide inter-individual variability. Our aim was to investigate the influence of polymorphisms of VKORC1 and CYP2C9 genes on the mean daily dose requirement of acenocoumarol. Methods: 205 chronic RHD patients, with mechanical heart valves and on acenocoumarol therapy, were recruited. Genotyping for VKORC1 (−1639G>A and 1173C>T) and CYP2C9 (*2 & *3 alleles) polymorphisms was done by PCR-RFLP. There was complete linkage disequilibrium between VKORC1 polymorphisms (r2 = 0.98, D′ = 1.0, LOD = 74.02). VKORC1 genotype distribution for GG/CC, GA/CT, and AA/TT were 57.6%, 36.1%, and 6.3%, respectively. CYP2C9 genotype distribution for *1/*1, *1/*3, *1/*2, *2/*2, and *2/*3 were 78.5%, 14.1%, 6.3%, 0.5%, and 0.5%, respectively. Patients with a wild type of both VKORC1 (−1639GG and 1173CC) and CYP2C9 gene variants required higher acenocoumarol dose compared to those with mutant genotype ( P = 0.023 and P = 0.008 respectively). On combined genotype analysis, patients having a combination of wild type of VKORC1 with wild type of CYP2C9 (44.4%) required higher daily dose compared to patients bearing heterozygous VKORC1 (−1639GA & 1173CT) with wild type of CYP2C9 (30.2%, P = 0.008). Conclusion: Presence of a mutant allele of VKORC1 (−1639A & 1173T) and CYP2C9 genes increased the odds of requiring a lower mean dosage of acenocoumarol. Studying the combination of genotypes in RHD patients could predict acenocoumarol dose requirement more accurately. |
| Databáze: | OpenAIRE |
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