Resistance to Warfarin Therapy among Egyptian Patients
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- Category: Vol. 84, December 2016
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Resistance to Warfarin Therapy among Egyptian Patients, AHMED A.H. AHMED, MANAL E. ABO FARHA, SHERIF N. AMIN and MAHA F. YOUSSEF
Abstract
Aim of the Study: To stratify the warfarin effect regarding the genotype of the patient in order to spot any racial or ethnic variations between Egyptians and the previously published international data. To spot any relation between patient gen-otype and resistance to warfarin therapy.
Methods: We performed a case-control study. Informed consent was obtained from each participant. We enrolled patients failing to reach a target INR of 2-3 after using large doses of warfarin (more than 15mg PO daily) as cases (n=36). Age and sex matched patients successfully reached target INR with usual doses were considered as controls (n=28). Both groups were screened for VKO-RC1-1629G >A and CYP 4502C9 variants.
Results: We found more males among the control group (53.6% males compared to 46.4% females) though statistically insignificant (p-value 0.44), while among cases females were more encountered (58.3% females compared to 41% males) which reached statistical significance (p-value 0.02). On testing for VKORC1 mutations, we found 47.2% of cases with mutant allele, all heterozygous. On testing the control group for the same mutation, we found 60.7% of subjects (n=17) with mutant allele, 3.6% (n=1) was homozygous (AA) genotype, though not achieving statistical significance (p-value=0.27). On testing for mutations affecting CYP4502C9 allele, we found 36.1% (n=13) of cases with mutant alleles, 11.1% (n=4), 22.2% (n=8) and 2.8% (n=1) with 1*/2*, 1*/3* and 3*/3* respectively. Regarding controls, we detected mutations in 46.4% (n=13) of which, 32.1% (n=9) had 1*/2* and 14.3 (n=4) had 1 */3 * alleles, though not achieving statis-tical significance (p-value=0.15). On correlating VKORC1 genotype with mean INR among controls, GG variants achieved a higher INR of 2.99 followed by genotype GA (INR=2.84).
Conclusion: The contribution of both gene mutations in warfarin resistance is marginal. There are yet uncovered factors leading to resistance to warfarin therapy.