ABSTRACT
BACKGROUND AND OBJECTIVE: Warfarin is the most widely prescribed oral anticoagulant worldwide. The narrow therapeutic index and the large variation in the inter-individual dose of warfarin are problematic, since the side effects can be lethal. Single nucleotide polymorphisms (SNP) in CYP2C9 and VKORC1 have been shown to significantly affect warfarin dosage toleration and this effect varies among different populations. We aimed to investigate the effect of these SNPs on warfarin dosage in a sample of Kuwaiti patients. METHODS: Kuwaiti patients who were taking a maintenance dose of warfarin were genotyped for CYP2C9*1, *2 and *3 and VKORC1 rs9923231, rs9934438, rs7294 and rs2884737. The association of these SNPs with the warfarin dose was evaluated. RESULTS: For CYP2C9, the CYP2C9 *1/*1 genotype required a higher dose (5.5 ± 3.3 mg/day) compared to non-*1/*1 (3.3 ± 1.7 mg/day) (p = 0.003). For VKORC1, the daily warfarin dose was significantly different (p = 0.001) among the three genotypes of rs9923231, rs9934438 and rs2884737, with carriers of the wild-type genotype requiring the highest dose compared to variant allele carriers (p ≤ 0.001-0.002). There was no association found between the daily warfarin dose and the rs7294 polymorphism. CONCLUSIONS: Our data showed that individuals carrying the wild-type allele of CYP2C9 or VKORC1 rs9923231, rs9934438 or rs2884737 are less sensitive than individuals with the variant alleles of these SNPs and therefore required a higher daily maintenance dose of warfarin. Our study confirms the association between SNPs in CYP2C9 and VKORC1 and warfarin dose tolerance in Kuwaiti patients.
Subject(s)
Anticoagulants/administration & dosage , Cytochrome P-450 CYP2C9/genetics , Polymorphism, Single Nucleotide , Vitamin K Epoxide Reductases/genetics , Warfarin/administration & dosage , Aged , Dose-Response Relationship, Drug , Drug Dosage Calculations , Female , Humans , Kuwait , Male , Middle AgedABSTRACT
The prevention and treatment of periodontal disease is based on accurate diagnosis, reduction or elimination of causative agents, risk management and correction of the harmful effects of the disease. The practice of risk assessment involves dental care providers identifying patients and populations at increased risk of developing periodontal disease. This can have a significant impact on clinical decision making. Risk assessment reduces the need for complex periodontal therapy, improve patient outcome and, ultimately, reduce oral health care cost. The awareness of risk factors also helps with the identification and treatment of co-morbidities in the general population as many periodontal disease risk factors are common to other chronic diseases such as diabetes, cardiovascular diseases and stroke.
