Læknablaðið : fylgirit - 03.01.2017, Qupperneq 28

X V I 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 9 1
28 LÆKNAblaðið/Fylgirit 91 2017/103
Megapedigrees with 6° relatives were electronically constructed. The risk
assessment program Boadicea™ was used to guide risk assessment and
testing. ROC curves were calculated with MedCalc™ on 175 randomly
chosen subset of women from BRCA2 families, 86 with positive results
and 90 with negative results.
Results: Pedigree size varied from 14-4198 individuals (average 379).
Non-overlapping families with the BRCA2 PV were 55 and 5 with the
BRCA1 PV. In all, 1400 counselees were tested for the two Icelandic
PV. Of 755 individuals in the BRCA2 families, 338 had a positive result,
while of the 59 individuals in the BRCA1 families 24 were positive. ROC
classification efficiency for the presence of BRCA2:c.771_775del5 increa-
sed significantly with pedigree size up to 3° relatives. Three other BRCA1
and one BRCA2 PV were found.
Discussion: Electronic mega-pedigrees based on data from electronic
genealogy database and cancer registry are a useful tool in cancer genetic
counselling. Typical handmade cancer pedigrees may loose valuable in-
formation since their size often does not include 3° relatives.
E 69 Bone disease in Monoclonal Gammopathy of Undetermined
Significance: Results from a Screened Population-Based Study
Sigrún Þorsteinsdóttir1, Sigrún H. Lund2, Ebba K. Lindqvist3, Maríanna
Þórðardóttir2, Gunnar Sigurðsson4, Rene Costello5, Debra Burton5, Hlíf
Steingrímsdóttir1, Leonore J. Launer6, Vilmundur Guðnason4, Guðný Eiríksdóttir4,
Kristín Siggeirsdóttir4, Tamara B. Harris6, Ola Landgren7, Sigurður Y. Kristinsson2
1Internal medicine services, Landspitali Hospital, 2The School of Health Sciences, University
of Iceland, 3Department of Medicine, Division of Hem, Karolinska University Hospital and
Karolinska Institutet, 4Hjartavernd, 5Center for Cancer Research, National Institutes of Health,
6National Institute on Aging, National Institutes of Health, 7Myeloma Service, Karolinska
University Hospital and Karolinska Institutet
sigrunth86@gmail.com
Background: Monoclonal gammopathy of unknown significance (MGUS)
is a precursor condition that precedes multiple myeloma. Our aim was to
analyze bone mineral density (BMD), bone volume, and risk of fractures
among individuals with MGUS in a screened population.
Methods: We performed a screening for MGUS using the AGES-
Reykjavik Study cohort, consisting of 5,764 individuals. Through serum
protein electrophoresis and free light chain analyses, 300 individuals
with MGUS and 52 with light chain MGUS were identified. Quantitative
computerized tomography (QCT) was performed to evaluate BMD and
bone geometry. Analysis of variance and Tukey’s honest significance test
were used to compare the groups. Hospital records were used to record
fractures. Cox proportional hazard models were used to compare risk of
fractures.
Results: No difference was found in BMD between subjects with MGUS
and others at the spine (p=0.21) or total hip (p=0.22). Individuals with
MGUS had a significant increase in bone volume compared to others in
the lumbar spine (p<0.001) and in total hip (p<0.001). Overall, the risk of
fractures was not significantly increased in individuals with MGUS as
compared to others (hazard ratio (HR): 1.19). Men with MGUS had a
significantly increased risk of fractures, compared to other men (HR: 1.49).
Conclusion: Our results from a screened population show that individu-
als with MGUS do not have a decreased BMD at the lumbar spine or hip.
Interestingly, we found that bone volume is increased in individuals with
MGUS, especially in men, who also have an increased risk of fractures.
E 70 MUC5B and Radiologic Subtypes of Interstitial Lung
Abnormalities in the AGES Study
Gunnar Guðmundsson1, Rachel K. Putman2, Tetsuro Araki3, Sigurður Sigurðsson4,
Thor Aspelund4, Vilmundur Guðnason4, Hiroto Hatabu3, Gary M. Hunninghake2
1Deparment of Pharmacology and Toxicology, Faculty of Medicine, UI, 2Pulmonary and
Critical Care Division, Harvard University, 3Department of Radiology, Harvard University,
4The Icelandic Heart Association
ggudmund@landspitali.is
Objectives: To replicate the association between ILA and the MUC5B
promoter polymorphism in the Age Gene/Environment Susceptibility
(AGES) study.
Methods: ILA were assessed via chest computed tomography (CT)
scans in 5,320 participants, using a sequential reading method. CT scans
with ILA were then sub-typed into phenotypes. Multivariable logistic
regression models were used for analyses.
Measurements and Main Results: In the AGES-Reykjavik cohort, ILA
was present in 378 (7%), 1726 (32%) had indeterminate ILA status and
3216 (61%) had no ILA on chest CT. Advanced age, increased tobacco
smoke exposure, and the MUC5B promoter polymorphism (odds ratio
[OR] of 2.7, 95% Confidence Interval [CI] 2.2, 3.2, P<.0001) were all
independently positively associated with ILA and with ILA with definite
fibrosis [OR=3.3, 95% CI 2.4, 4.4, P<.0001] in multivariable analyses in
the AGES-Reykjavik study. The MUC5B promoter polymorphism was
associated with all radiologic subtypes of ILA with varying effect sizes,
including the phenotype of UIP [OR=3.7, 95% CI 1.9, 7.4, P=0.0002],
probable UIP [OR=3.5, 95% CI 2.4, 5.0, P<.0001], possible UIP [OR=2.8,
95% CI 2.1, 3.7, P<.0001]. Also, somewhat surprisingly the MUC5B
promoter polymorphism was also positively associated with CT findings
not consistent with UIP [OR=1.9, 95% CI 1.3, 2.6, P=0.0002].
Conclusions: The MUC5B promoter polymorphism is associated with
ILA. Separately MUC5B is associated with all radiologic subtypes of ILA.
These findings provide further evidence of the importance of the MUC5B
promoter polymorphism in a broad spectrum of early and/or mild stages
of pulmonary fibrosis.
E 71 The influence of obesity onresponse to TNF- a inhibitors in
psoriatic arthritis
Pil Højgaard1, Bente Glintborg1, Lars Erik Kristensen2, Björn Guðbjörnsson3, Jón
Þorvarður Löve4, Lene Dreyer1,5
1Gentofte Hospital,Rigshospitalet, Department of Rheumatology, 2Bispebjerg and
Frederiksberg Hospital, Parker Institue, 3Landspítali University Hospital, Center for
Rheumatology Research (ICEBIO), 4Faculty of Medicine, University of Iceland, Department for
Scientific Affairs, Landspitali University Hospital, 5University of Copenhagen
bjorngu@landspitali.is
Objectives: To investigate theimpact of obesity on response to TNFi
treatment in PsA.
Methods: Observational cohort study based on the Danish and Icelandic
biologics registries. Kaplan-Meier plots, Cox and logistic regression
analyses were performed to study the impact of obesity (BMI ⩾ 30
kg/m 2 ) onTNFi adherence and response after 6 months (according to
ACR20/50/70% improvement). Subanalyses studied the impact of obesity
according to gender, TNFi type and nationality.
Results: Among 1943 PsA patients (193 Icelandic) identified in the
registries, 1271 (65%) had availableBMI and 408 (32%) were obese. The
median follow-up-time was 1.5 years [IQR 0.5-3.9]. Obese patients had
higher baseline disease activity, for example, 28-joint DAS [mean 4.6 (SD
1.2) vs 4.4 (1.2)]; CRP [median 9 mg/l (IQR5-19) vs 7 (3-18)] and VAS-pain
[66 mm (IQR 48-76) vs 60 (38-74)], compared with non-obese patients (all