UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://events.um.edu.mt/scisem/
Email: scisem@um.edu.mt
Abstract form
Title: Genetic studies of osteoporosis
Presenter: Dr. Christopher Vidal, PhD
Contact address: MLS BioDNA Ltd, KBIC rooms 2150 – 2160, Industrial Estate,
Kordin
Tel: +356 23980148
Fax: +356 23980161
Email: christophervid@gmail.com
Presentation date: Monday 19th November 2007
Abstract
In this study both association and linkage approaches were used to identify genes that might
be responsible for osteoporosis in the Maltese population. A statistically significant
difference was observed in the distribution of genotype and haplotype frequencies, between
women having a normal and a low BMD, of polymorphisms within the promoter region of
the osteoprotegerin gene (TNFRSF11B). A genome-wide scan was performed in two
extended families with a high incidence of osteoporosis. Evidence of linkage was observed
to a marker at 11p12 where a non-parametric LOD score (NPL) of 5.77 (p=0.0006) was
obtained. A maximum heterogeneity LOD (HLOD) score of 2.55 for this region was
obtained for the dominant mode of inheritance. Following fine mapping, the critical interval
was narrowed to a region that is 52.94cM. The TRAF6 gene found at this locus was
sequenced to try to identify any mutations. Three sequence variants were identified in
TRAF6, two found in introns and the third one found in the promoter region, at position -721
upstream from the transcriptional start site. Three affected members were heterozygous for
this variant, while only two heterozygotes were identified (population frequency 1.1%),
when screening the general population (n=175). Studies of this variant on its possible role in
gene expression are indicative of an effect on gene expression, possibly by collaboration
with other transcriptional factors further upstream in the promoter. An increase in TRAF6
expression can result in increased osteoclastogenesis and therefore an increased risk of
osteoporosis.