Abstract

THE INCIDENCE OF F8 GENE MUTATION IN SUDANESE PATIENTS AT RISK OF BOTH VENOUS AND ARTERIAL THROMBOSIS UNDER PROLONG USE OF WARFARIN TREATMENT

Dr. Arwa A. A. Mohammed Ahmed*, Prof. El-Sheikh A. El-Obeid,
Dr. Hind Abushama

Abstract

Warfarin is a narrow therapeutic index agent. Complications from warfarin therapy occur even with proper monitoring . According to direct observations and very interesting findings in other research studies there is a need to detect the possibility of F8 gene mutation incidence that lead to an over expression of factor VIII protein which is essential for the formation of blood clots. The aim of this study is to investigate if there is a variation in F8 gene promoter region among Sudanese patients under warfarin therapy. This investigation was done by using Polymerase chain reaction -Restriction Fragment Length Polymorphism (PCR-RFLP) technique. The second aim is to find a possible association with the prolonged use of warfarin therapy and variation in F8 gene promoter region , to find a possible association between prolonged warfarin therapy and the incidence of thrombosis. Finally to detect if males are at higher risk of treatment failure compared to females. The investigation of F8 gene promoter region shows that most of the mutated samples belonged to males while only one female had a mutation . Six different samples were found to be mutant and two of them refer to fragment 1F from < -64 - 279 > , 3.1% of males had the genotype C-C which is the homozygous mutant type , while four refer to fragment AR from < 361 - 600> , 4.6% males had the homozygous mutant allele C-C while only 1.5% female . There was a significant relation between the prolonged use of warfarin therapy and the elevation of the severity level.

Keywords: F8 gene, INR: International Normalized Ratio, promoter region, PT: Prothrombin Time, MVR: Mechanical Heart Valves Replacement, PCR: Polymerase chain reaction.