2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
P09.105
the positive association of +1858c>t polymorphism in PtPN22
gene with type 1 diabetes is replicated in Russian population.
E. Grineva, Y. Kudryashova, A. Kostareva, A. Kozyreva, V. Gryzina, E. Shlyakhto;
Almazov Federal Centre of Heart, Blood and Endocrinology, St. Petersburg,
Russian Federation.
The nonsynonymous single nucleotide polymorphism (SNP) +1858C>T
within the PTPN22 gene coding the lymphoid tyrosine phosphatase
has been associated with type 1 diabetes and other autoimmune diseases
such as autoimmune thyroiditis, rheumatoid arthritis and lupus
erythematosus. In spite of the low frequency of this polymorphism
its association with T1D has been confirmed in several populations.
The aim of this study was to replicate type 1 diabetes association with
+1858C>T SNP within the PTPN22 gene in Russian population. MA-
TERIAL AND METHODS: the study population included 150 children
and adolescents with T1D and 250 unrelated healthy controls. The
rs2476601 in PTPN22 (C1858T) was genotyped using restriction fragment
length polymorphism. RESULTS: We replicated for the first time
in a Russian population the association of the 1858T allele with an
increased risk for T1D [ allele T vs. CC: OR (95%) = 1.6 (1.0-2.4); p =
0.002]. CONCLUSION: Our results provide further evidence that the
+1858C>T polymorphism is primarily associated with type 1 diabetes
and represents a susceptibility factor in Russian population.
P09.106
sequencing of candidate genes in Rapid Eye movement sleep
Behaviour Disorder
S. L. Girard 1 , P. Dion 1 , L. Xiong 1 , J. Montplaisir 2 , R. B. Postuma 3 , G. A. Rouleau
1 ;
1 Center of Excellence in Neuromics, Montréal, QC, Canada, 2 Centre d’étude du
sommeil, Hopital Sacré-Coeur, Montréal, QC, Canada, 3 Department of Neurology,
Mcgill University, Montréal, QC, Canada.
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a sleep
disturbance that involves a loss of muscular atonia in the dream-associated
REM phase. RBD is known to produce a violent dream-actingout
behaviour and, thus, represents a risk of injury for both RBD affected
individuals and their bed partner. The prevalence of RBD is 0.38%
in the general population and 0.5% in the elderly population. Several
studies have shown that there is an up to 90% male predominance
in this disease, which suggests a potential link to chromosome X. To
date, no genetic studies have been reported for RBD. Strong evidences
lead us to think that there might be a strong relationship between
RBD, Parkinson’s disease (PD) and Lewy Body Dementia (LBD). We
followed this hypothesis to build an interactome of the genes shared
by PD and LBD, using experimentally demonstrated human proteinprotein
interactions available online. Using this interactome as a basis
for the mechanism that may underlie RBD, we selected 25 candidate
genes, according to different criteria: 1) genes carrying known mutations
in either PD or LBD; 2) genes that have strong interactions with
genes carrying known mutations in either PD or LBD; 3) genes implicated
in other neurodegenerative disorders; and 4) genes located on
chromosome X. These candidate genes are currently being screened
for mutations in a cohort of 100 RBD patients, which constitutes one
of the first attempts to elucidate the genetic mechanisms underlying
RBD.
P09.107
thrombophilic genes in women with recurrent miscarriage
F. M. Kaneva1 , V. L. Akhmetova1 , A. Z. Gilmanov2 , E. K. Khusnutdinova1 ;
1 2 Institute of Biochemistry and Genetics, Ufa, Russian Federation, Bashkir
State Medical University, Ufa, Russian Federation.
Recurrent miscarriage (RM) is a significant actual problem of modern
obstetrics with many etiologies. Thrombophilias is one of the most
common cause of RM (40-75%). The contribution of specific inherited
thrombophilic genes to this disorder has remained controversial.
We carried out the study of polymorphic loci MTHFR A1298C, FGB
-455G/A, ACE I/D, TPA25 I/D in 4 groups of women with RM: the first
group - women with threat of interruption of pregnancy without the
burden obstetric anamnesis (n=111), 2 - with spontaneous abortions
(n=57), 3 - with the stood pregnancy (n=97), 4 - with the burden obstetric
anamnesis (syndrome of loss of a fetus, habitual miscarriage,
stood pregnancy) (n=37), and women with normal physiological pregnancy
(n=83). No differences in the frequency of specific gene mutations
were detected when women with RM were compared with control
women (p>0.05). Only homozygous genotype DD of the gene ACE
was associated with RM (OR=2.67, 95%CI 1.11-6.48, p