Læknablaðið : fylgirit - 05.01.2015, Page 67

X V I I V Í S I N D A R Á Ð S T E F N A H Í
F Y L G I R I T 8 2
LÆKNAblaðið/Fylgirit 82 2015/101 67
proliferation of plasma cells in the bone marrow and overproduction of
monoclonal immunoglobulins in serum or urine. Familial aggregation
of MM has been reported by several authors but the underlying genetic
cause of the disease is uncertain and the impact of family history on
survival is unknown. The aim of our study was to compare survival in
MM patients with family history of lymphoproliferative disorders (LPD)
to MM patients without family history of LPD.
Methods and data: MM patients and their first-degree relatives were
identified using the nationwide Swedish Registries. Information on mal-
ignancies in relatives of MM patients was obtained by record-linkages
to the Swedish Cancer Registry. In statistical analysis all data were
adjusted for age, sex and year at diagnosis.
Results: A total of 13,926 MM patients diagnosed in 1957-2005 were
included of whom 630 had a linkable first-degree relative, a total of
876 relatives. Compared to MM patients without family history, MM
patients with family history had a significantly lower risk (HR 0.85;
95% CI 0.77-0.92, p<0.001) of death. The difference was greatest in the
youngest age group (0.79; 0.65-0.96, p<0.05) and was more prominent in
males than in females (1.20; 1.01-1.43, p<0.05).
Conclusions: This large population-based study showed for the first
time that survival in MM patients with family history of LPD was
superior to MM patients without family history. The underlying expl-
anations for our findings need to be established by further studies.
V 31 The role of microRNA in gene regulation
Linda Hrönn Sighvatsdóttir, Sigrún Guðjónsdóttir, Stefán Sigurðsson
Biomedical Center, Faculty of Medicine, University of Iceland
lhs4@hi.is
Introduction: Gene expression by RNA polymerase II (RNAPII) is
not exclusively regulated at the initiation step but also during the
elongation phase of transcription. Specific transcription factors such
as TCEA1 enhance transcription elongation by reactivating paused or
stalled RNAPII, allowing transcription to proceed. Gene expression can
also be regulated by microRNAs by their binding to the 3‘ untranslated
(3´UTR) region of target mRNA. This binding of the microRNA to
the 3´UTR of the mRNA results either in downregulation of protein
translation or cleavage of the mRNA target. Our studies are aimed at
studying the transcription elongation factor TCEA1, in particular its role
in reactivating paused RNAPII and the role of microRNA in regulating
TCEA1 expression.
Methods and data: The 3´ UTR region of TCEA1 was cloned down-
stream of a luciferase reporter. This reporter plasmid was co-transfected
with different miRNA all found to have conserved binding sites in the
3´ UTR of TCEA1 based on microRNA and microRNA target databases.
Endogeneous TCEA1 expression levels where also measured by using
highly specific TCEA1 antibody.
Results: We will present data that shows that TCEA1 expression is
regulated by microRNA. This regulation is seen both when using the
luciferase expression system as well as downregulation of endogenous
TCEA1 measured by Western blotting.
Conclusions: The microRNA family affecting TCEA1 expression is
frequently found to be downregulated in various types of cancer. This
raises a question regarding the role of TCEA1 in cancerous tissue,
specifically the importance of efficient transcription elongation and gene
expression.
V 32 Algengi erfðabreytileika sem valda skorti í lektínferli
komplímentkerfisins í íslenskum blóðgjöfum
Margrét Arnardóttir1,2, Helga Bjarnadóttir1, Björn Rúnar Lúðvíksson1,2
1Ónæmisfræðideild Landspítala, 2læknadeild Háskóla Íslands
margret84@gmail.com
Inngangur: Lektínferill komplímentkerfisins (LP) er ræstur af mynstur-
þekkjandi prótínum (PRPs). Þetta geta ýmist verið mannan-bindi
lektín (MBL), fíkólín (1-3) eða kollektín-11 (CL-11). Í flóka með PRPs
eru serín próteasar (MASPs (1-3)) og prótín án ensímvirkni (MAp1 og
sMAP). Þekktar stökkbreytingar valda skorti í prótínum lektínferilsins.
Einstaklingar með MBL2 arfgerðirnar O/O eða XA/O eru með MBL
skort. Áhrif D120G samsætunnar í MASP2 geninu og 1637delC samsæt-
unnar í FCN3 geninu á magn prótína í sermi er genaskammtaháð þannig
að arfhreinir einstaklingar hafa ómælanlegt MASP-2 eða fíkólín-3 í
sermi. Markmið þessarar rannsóknar var að meta algengi samsæta sem
valda skorti í LP.
Efniviður og aðferðir: Safnað var 500 blóðsýnum frá Blóðbankanum
og DNA einangrað með hásaltsaðferð. Til að greina þekktar stökk-
breytingar í MBL2 geninu (X/A/B/C/D) var framkvæmd rauntíma
kjarnsýrumögnun (real-time PCR) með þekktri bræðslumarksgreiningu.
Til að greina 1637delC var notast við skerðibútagreiningu. Til að greina
D120G var notast við PCR-SSP (sequence specific primer PCR).
Niðurstöður: Alls voru 498 blóðgjafar 1637delC og D120G arfgerða-
greindir. Fimmtán (3%) greindust 1637delC arfblendnir (C/-) og 39
(7,8%) mældust D120G arfblendnir (D/G). Alls voru 494 einstaklingar
arfgerðagreindir fyrir fimm stökkbreytingum í MBL2 geninu. Algengi
arfgerða sem valda háum MBL styrk (YA/YA, XA/XA og YA/O) og
arfgerða sem valda MBL skorti (XA/O og O/O) var 92,1% og 7,9%.
Ályktanir: Áætlað algengi 1637delC og D120G samsætanna er því 0,015
og 0,041. Við getum reiknað með að um 1:4500 Íslendinga eru með
fíkólín-3 skort (~70 einstaklingar) og 1:640 (~500) með MASP-2 skort.
Niðurstöður okkar eru sambærilegar við genatíðni í sams konar þýðum.
Hins vegar er algengi MBL skorts (7,9%) í okkar rannsóknum nokkuð
lægri en í sambærilegum þýðum af hvítum evrópskum uppruna (16%).
V 33 Lichen derived metabolites show synergistic effects with
known cancer drugs against cancer cells
Margrét Bessadóttir1,2, Edda A. Skúladóttir1, Sindri Baldursson1, Sesselja
Ómarsdóttir2, Helga M. Ögmundsdóttir1
1Faculty of Medicine, University of Iceland, 2Faculty of Pharmaceutical Science, University of
Iceland
mab24@hi.is
Introduction: Protolichesterinic acid (PA) is the major biologically
active secondary metabolite of the lichen Cetraria islandica. PA has anti-
proliferative effects on several types of cancer cells, but no effect on
normal skin fibroblasts and is an inhibitor of 5- and 12-lipoxygenase
(LOX). Usnic acid (UA) (from Cladonia arbuscula) has a wide range of
biological activities, e.g. anti-inflammatory, anti-viral and anti-bacterial
activity. UA affects pH gradients and inhibits growth and proliferation
of several cancer cells. Fatty acid synthase (FASN) is up-regulated in a
variety of cancers. Overexpression of human epidermal growth factor
receptor 2 (HER2) has been linked to increased translation of FASN.
The chemical structure of PA is very similar to a known FASN inhibitor,
C75. FASN inhibition interacts synergistically with HER2 targeted
drug (e.g. lapatinib) in breast cancer cells and can overcome resistance.