Abstract:
Von Willebrand’s disease is an autosomally inherited bleeding disorder caused by a qualitative and/ or quantitative abnormality of von Willebrand’s factor . It is one of the most common inherited bleeding disorders based on statistics from developed countries. Human von Willebrand’s factor is a large multimeric protein that plays an important role in the adhesion of platelets to the sub endothelium. It also acts as a carrier for coagulation factor VIII. Its deficiency and or dysfunction may result to either bleeding or thrombosis. After an extensive literature search, we were unable to find documented report on von Willebrand’s disease in Nigeria. The study evaluated the functional assays of von Willebrand’s factor gene in the three major ethnic groups of Nigeria and sequenced exon 28 of the VWF gene (genomic DNA) in healthy adults and adults with bleeding history. The aim was to define the normal populations across the von Willebrand’s factor gene, to provide a framework for investigating von Willebrand’s factor related bleeding disorder for our population. Ninety subjects were enrolled into the study; forty-five with a history of bleeding and forty-five without a history of bleeding. These subjects were selected randomly from the three major ethnic groups of Nigeria; Hausa, Igbo and Yoruba. Thirty subjects were enrolled in each of the ethnic groups. Experimental procedure consists of; full blood count, using automated haematology analyzer, coagulation assay, using a semi auto Coagulometer. ELISA techniques were used for the investigation of von Willebrand’s functional assay ; standard PCR amplification of exon 28 of the von Willebrand’s factor gene and re-sequencing of the PCR amplification product by direct DNA sequencing ,using BigDye terminator chemistry. With 45 subjects in each of the groups the study has a 99% power to detect a difference of 0.046 between mean values, at p<0.05(two tailed). Unpaired t-test and chi square test were used were applicable for the statistical analysis. Von Willebrand functional assays [VWF: Ag and VWF: CB] showed significant difference between the index cases and the control group (p<0.05). Eight SNPs were detected in our population; rs 216310, rs 1800385, rs1800384, rs1800383, rs1800386, rs216311, rs216312 and rs1800381. rs1800383 (D1472H), rs1800386 (Y1584C) and rs216311 (T1381A) associated significantly with bleeding in this study, were also detected in some of the control subjects. rs 216310(T1547), rs 1800385(V1565L), rs1800384 (A1515), were not detected in three samples from Yoruba ethnic group, no ethnic specific difference was noted in this study.
