Scientific Poster Session III - Original Research

Original Research
  Monday, November 13, 2023
  01:00 PM–02:30 PM

Abstract

Introduction: The inter-individual variability in response to warfarin is attributed to demographic, environmental and genetic factors. The two reduced function alleles CYP2C9*2^rs1799853 and CYP2C9*3^rs1057910 are the most common (SNPs) in the gene encoding CYP2C9 involved in warfarin's metabolism. Individuals carrying either one or both alleles are classified as intermediate and slow-metabolizers, respectively. The low prevalence or unavailability of data on the functional effect(s) of the other alleles hinders their acquisition of significant clinical applicability.

Research Question or Hypothesis: Our study aimed to first, determine the prevalence of the *2 and *3 alleles, and other functionally significant alleles (*5 and *8), or alleles with no clinically established functionality (*41 and *46) in a cohort of Syrians;second , investigate the impact of genotypes on warfarin’s stable maintenance doses, time required to reach therapeutic INR values, and the frequency of bleedings.

Study Design: A cohort study design was adapted to investigate the relationship between patients’ genotypes and warfarin therapeutic outcomes.

Methods: Allele frequency was identified via standard sequencing of the specific polymerase chain reaction (PCR) products of the CYP2C9 gene in 138 individuals; healthy subjects (n=44) and patients on warfarin (n=94)

Results: The weekly dose ranged between 4.5-140 mg in the total cohort. The frequency of the *2, *3, *46 and *41 alleles were 14.8%, 8.5%, 0.36% and 0.72%, respectively. Sixty (43.6%) of the genotyped subjects (n= 138) had at least one exonic variant allele. The mean weekly dose of warfarin was 37.9 ±15.5 mg for the wild type (CYP2C9*1*1) patients, whereas carriers of at least one copy of the reduced function SNPs (*2,*3,*46) demanded a significantly lower dose (28.2 ±11.42 mg). Of the twenty-five patients who experienced hemorrhagic accidents, 16 (64%) had =1 reduced function allele.

Conclusion: Our findings emphasize the significance of CYP2C9 genotyping prior to commencing warfarin therapy in order to optimize dose and ensure effectiveness and safety.

Presenting Author

Weam Aldiban Ph.D

Authors

Majd Aljamali Ph.D
Damascus University

Lama Youssef Ph.D
Damascus University