2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
cohorts from Japan (P= 3.23 x 10 -8 and P=7.45 x 10 -8 ). We also found a
Japanese cohort of systemic lupus erythematosus (SLE) that had the
similar genotype distribution with RA cohorts. These disease-associated
SNPs, rs3766379 and rs6682654 have been shown to increase
their expression in luciferase and allele-specific transcript quantification
assays. Furthermore, we indicated that rs6682654 locates on the
binding site of USF-1 in CD244 gene and affect on the regulation of
CD244 expression via USF-1. CD244 is a novel genetic risk factor for
RA and may have a role for autoimmunity in RA.
P09.110
shared genetic susceptibility in primary and secondary restless
legs syndrome: A case-control association study in end-stage
renal disease patients
B. Schormair 1,2 , J. Plag 1,2 , D. Roeske 3 , N. Groß 4 , B. Müller-Myhsok 3 , W. Samtleben
5 , U. Heemann 6 , T. Meitinger 1,2 , J. Winkelmann 1,4,2 ;
1 Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany,
2 Institute of Human Genetics, Technische Universität München, Munich, Germany,
3 Max Planck Institute of Psychiatry, Munich, Germany, 4 Department of
Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich,
Germany, 5 Department of Internal Medicine, Nephrology Division, University of
Munich - Klinikum Grosshadern, Munich, Germany, 6 Department of Nephrology,
Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
There are two forms of the restless legs syndrome (RLS), primary
RLS (pRLS) and secondary RLS. The most common form of secondary
RLS is uremic RLS (uRLS) in end-stage renal disease (ESRD). In
recent genome-wide association studies (GWAs) we have identified
variants (MEIS1, BTBD9, PTPRD, and MAP2K5/LBXCOR1) as risk
factors for familial and sporadic pRLS. It is not known if the same genetic
variants are implicated in uRLS..
We therefore analysed the contribution of the pRLS risk factors to
uRLS in a case-control association study in ESRD patients. A total of
642 ESRD patients were scrutinized for symptoms of RLS in face-toface
interviews. 199 were classified as RLS-positive cases (38 familial,
161 sporadic), 443 as RLS-negative controls. Basic dialysis parameters
of both groups did not differ significantly (duration of dependence
on dialysis, P>0.09; average time on dialysis per week, P>0.7). We
genotyped 10 pRLS-associated SNPs in these groups using the Sequenom
iPLEX technology. Statistical analysis was performed using
logistic regression with age and sex as covariates. After correction
for multiple testing, MEIS1 (rs12469063, P corr = 0.006) and BTBD9
(rs3923809, P corr = 0.002), were associated with uRLS. SNPs in PT-
PRD and MAP2K5/LBXCOR1 did not show any association (P>0.15)
with uRLS..
These results support the concept of a partially overlapping genetic
predisposition mechanism in pRLS and uRLS.
P09.111
Polymorphisms in genes with emerging roles in regulation of
immune response and their effect on sarcoidosis susceptibility
in slovenian patients
A. Maver1 , I. Medica1 , B. Salobir2 , M. Tercelj2 , B. Peterlin1 ;
1 2 Institute of Medical Genetics, Ljubljana, Slovenia, Department of Pulmonary
Diseases and Allergy, Ljubljana, Slovenia.
Sarcoidosis is a chronic inflammatory disease characterised by appearance
of granulomas in various organ systems. Among possible
causes, genetic factors have been implicated in sarcoidosis aetiology.
We have performed the search for novel candidate genes utilising integrative
genomics approach, which was based on data from reported
transcriptional, proteomic and linkage association studies in sarcoidosis.
The search revealed several potential previously uncharacterised
candidate genes, among which genes that have recently been implicated
in the pathogenesis of inflammatory lung diseases, were selected.
Here we present data on association of polymorphisms -1260/ C>A
in the CYP27B1 gene, Lys198Asn in the EDN1 gene and Ile105Val in
the GSTP1 gene with sarcoidosis in a group of 178 Slovenian patients
in comparison with 272 healthy controls. Genotypes were obtained
by multiplex polymerase chain reaction using allele specific primers
(ASO-PCR). Genotype and allelic frequencies in patients and controls
were statistically analysed for association with the disease.
There was no significant association of genotypes or allelic variants
of polymorphisms in any of the three genes with susceptibility to sarcoidosis.
Minor effects of polymorphisms in selected candidate genes should
be analysed in subsequent studies investigating a larger sample of
patients and controls.
P09.112
Recurrent rearrangements in synaptic and neurodevelopmental
genes support the existence of shared biological pathways
between schizophrenia, autism and mental retardation
A. Guilmatre1 , C. Dubourg2 , A. Mosca1,3 , S. Legallic1 , A. Goldenberg4 , V.
Drouin-Garraud4 , V. Layet5 , A. Rosier6 , S. Briault7 , F. Bonnet-Brilhault8 , F. Laumonnier8
, S. Odent9 , G. Le Vacon1 , G. Joly-Helas4 , V. David2 , C. Bendavid2 ,
C. Impallomeni10 , E. Germano10 , G. Di Rosa10 , C. Barthelemy8 , C. Andres11 , L.
Faivre3 , T. Frébourg1 , P. Saugier-Veber1 , D. Campion1 ;
1 2 Inserm U614 and Rouen University Hospital, Rouen, France, UMR
6061CNRS, University of Rennes I, Rennes, France, 3Department of Genetics,
Dijon University Hospital, Dijon, France, 4Department of Genetics, Rouen University
Hospital, Rouen, France, 5Department of Genetics, Le Havre Hospital,
Le Havre, France, 6Centre de Ressources Autisme de Haute Normandie, Saint
Etienne du Rouvray, France, 7Department of Genetics, University Hospital,
Angers, France, 8Inserm U930, Université François-Rabelais and University
Hospital, Tours, France, 9Department of Genetics, University Hospital, Rennes,
France, 10Department of Medical and Surgical Pediatrics, University Hospital,
Messina, Italy, 11Inserm U 619, Tours, France.
Comparative genomic hybridization (array-CGH) studies have suggested
that rare copy number variations (CNVs) at numerous loci are
involved in the aetiology of mental retardation (MR), autism (ASD)
and schizophrenia. We have investigated, using QMPSF (Quantitative
Multiplex PCR of Short fluorescent Fragments), 28 candidate loci
previously identified by array-CGH studies for gene dosage alteration
in 247 subjects with MR, 260 with ASD, 236 with schizophrenia or
schizoaffective disorder and 236 healthy controls. We show that the
collective frequency of CNVs at these loci is significantly increased in
autistic patients, patients with schizophrenia and patients with MR as
compared with controls (p