Molecular Characterization Of Exon 28 Of The Vwf Gene In Nigerian Population

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