2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
nal study were genotyped among 127 MDD (DSM-IV criteria) and 127
healthy controls from the Chinese population. Samples were investigated
by using PCR-RFLP.
Results: There were a positive association of allele T of the marker
SNP3 with MDD (rs3730358, p = .024). Haplotype analysis showed
that the frequency of a four-AKT1 SNP1/2/3/4 haplotype (AGTG)
was significantly higher in MDD patients (0.054) than that of controls
(0.011) (p = .011).
Conclusion: Our study provides support for the hypothesis that AKT1
is a susceptibility gene for MDD.
P09.070
Genotyping of the serotonin transporter promoter polymorphism
in a Dutch major depression cohort
E. C. Verbeek 1 , M. R. Bevova 1 , P. Rizzu 1 , P. Heutink 1 , W. J. Hoogendijk 2 ;
1 Department of Medical Genomics, VU University Medical Center, Amsterdam,
The Netherlands, 2 Department of Psychiatry, VU University Medical Center,
Amsterdam, The Netherlands.
Major Depressive Disorder (MDD) is a psychiatric disorder with high
public health significance: it is currently the leading cause of disease
burden in western civilization and the fourth cause on a global scale.
People suffering from MDD show persistent dysphoria and additional
cognitive symptoms.
Various theories about the causes of MDD exist and a genetic component
is recognized in most of them. However, in complex disorders it is
a challenge to discover high impact mutations and polymorphisms.
A genetic region that has been investigated in relation to neuropsychiatric
disorders is serotonin-transporter-linked polymorphic region
(5-HTTLPR). Serotonin itself has been implicated in the cause of MDD
and thus regulation of serotonin availability by the serotonin transporter
provides a region of interest. The 5-HTTLPR has a long variant
and a short variant, where a deletion has taken place. Within the
deleted region a single nucleotide polymorphism (SNP) can be found,
rs25531. This SNP has also been investigated in relation to psychiatric
illnesses, including MDD. Many of these studies are limited by a small
sample size and might therefore not find verifiable associations.
In this study we use the MDD-cohort (3840 samples) of the genetic association
information network (GAIN) to unearth possible associations
between MDD and the 5-HTTLPR.
The region consists of repeats and has a high GC-content. For determining
a long or short genotype we use fluorescent primers to amplify
the region and separate products with capillary electrophoresis. MspI
was used to distinguish different genotypes of rs25531.
P09.071
Relationships between genes of interleukin 10 gene cluster and
mood and anxiety disorders
K. Koido 1 , T. Eller 1 , K. Kingo 1 , S. Koks 1,2 , T. Traks 1 , J. Shlik 3 , V. Vasar 1 , E. Vasar
1 , E. Maron 1,4 ;
1 University of Tartu, Tartu, Estonia, 2 Estonian University of Life Sciences, Tartu,
Estonia, 3 University of Ottawa, Ottawa, ON, Canada, 4 North Estonian Regional
Hospital, Tallinn, Estonia.
Major depressive disorder (MDD) and panic disorder (PD) belong to
the most prevalent mental diseases, affecting respectively 10% and
3% of general population. Alterations in immune system have been
implicated in the onset and development of MDD and PD. We studied
the relationship between single-nucleotide polymorphisms (SNPs) of
genes from interleukin 10 (IL10) chromosomal region 1q32 and MDD
and PD. The association study design was used: 38 SNPs from 10
genes and regions between them of IL10 gene cluster were analyzed
in 522 unrelated patients and in 356 healthy control subjects. All subjects
were individuals of Caucasian origin living in Estonia. Patients
were divided into two groups according to diagnosis: comparison of
allelic frequencies was performed between control group and MDD
patients (n=313), PD patients (n=209), and the whole patient group
(n=522). Both MDD and PD groups included ‘pure’ phenotypes as well
as phenotypes comorbid to other mood and anxiety disorders. SNPlex
Genotyping System was applied for genotyping, following association
and haplotype analyses with Haploview program. Association analysis
of 38 SNPs revealed the most prominent relationship between MDD,
PD, and the whole patient group and SNP (rs1539243) in IKBKE gene
(inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase
epsilon) (allelic p values 0.02, 0.0009, and 0.0011, respectively). Hap-
lotype analysis revealed seven haplotype blocks in all tested groups of
patients compared to healthy controls. None of frequencies of haplotypes
differed significantly. Results show that IKBKE gene from 1q32
chromosomal region may possibly be related to mood and anxiety disorders.
P09.072
Failure to detect microduplication 22q11.2 among a group of
schizophrenia patients with multiple Ligation Dependent Probe
Amplification (MLPA)
E. Nourian 1 , M. Noruzini 2 , H. Galehdari 3 , M. Sadeghizadeh 1 , M. Behmanesh 1 ;
1 Department of Genetics, Faculty of Sciences, Tarbiat Modares University, Tehran,
Islamic Republic of Iran, 2 Department of Hematology, Faculty of Medical
Sciences, Shahid Chamran University, Ahwaz, Islamic Republic of Iran, 3 Department
of Medical Genetics ,Faculty of Medical Sciences, Shahid Chamran
University, Ahwaz, Islamic Republic of Iran.
Chromosome aberrations have long been studied in an effort to identify
susceptibility genes for schizophrenia. Chromosome 22q11.2 microdeletion
is associated with DiGeorge and Velocardiofacial syndromes
(DG/VCF) and provides the most convincing evidence of an association
between molecular cytogenetic abnormality and schizophrenia. In
addition, this region is one of the best replicated linkage findings for
schizophrenia. Recently, the reciprocal microduplication on 22q11.2
has been reported as a new syndrome. Preliminary data indicates that
individuals with these duplications also suffer from neuropsychiatric
disorders. In this study we have investigated the appropriateness of
testing schizophrenia patients for the 22q11.2 microduplication. We
used multiplex ligation-dependent probe amplification (MLPA) to measure
copy number changes on the 22q11.2 region in a sample of 120
patients with schizophrenia. Our results corroborate the prevalence of
the 22q11.2 microdeletion in patients with schizophrenia and clinical
features of DG/ VCFS and do not suggest an association between
22q11.2 microduplication and schizophrenia.
P09.073
Role of the Estrogen Receptor (EsR1 Pvuii and EsR1 325 c>G)
and Progesterone Receptor (PROGiNs) polymorphisms in
genetic susceptibility to migraine in a North indian Population
G. Joshi, S. Pradhan, B. MITTAL;
Sanjay Gandhi Postgraduate Institute of Medical Sciences, LUCKNOW, India.
We aimed to explore the single-locus, haplotype, epistasis patterns and
contribution of ESR1 PvuII (rs2234693), ESR1 325 C>G (rs1801132)
and PROGINS (rs1042838) polymorphisms in genetic susceptibility
to migraine by analyzing 613 subjects consisting of 217 Migraine patients,
217 Healthy controls (HC) and 179 patients with Tension Type
Headache (TTH). Entire data was analyzed by taking Bonferroni corrected
P value into account. We found significant association of TT
genotype (OR=3.458; CI=1.757-6.806; P value=0.0003) and T allele
(OR=1.729; CI=1.309-2.284; P value=0.0001) of ESR1 PvuII SNP with
migraine when compared with HC. Significant association was seen
only in female migraine patients. Moreover, higher risk of TT genotype
and T allele was limited to migraine with aura (MA) than migraine without
aura (MO). In case of ESR1 PvuII, risk in migraine patients could
fit in the recessive model, but no risk was observed when TTH patients
were compared with HC. However, in ESR 325 G>C polymorphism, no
significance was seen in any of the models. In PROGIN polymorphism,
significant low risk at genotypic and allelic levels was seen when migraine
patients were compared with HC. ESR1 PvuII TT * ESR1 325
C>G CG genotype, PROGINS A1A2 * ESR1 325 C>G CG genotype
and ESR1 PvuII CT * PROGINS A1A2 interacted significantly, but the
significance was lost after Bonferroni correction. In conclusion, ESR1
PvuII polymorphism is a significant risk factor for migraine particularly
in females and MA patients, but, ESR 325 C>G and PROGINS polymorphisms
are not associated with migraine susceptibility in North Indian
population.
P09.074
Association of a non-coding mtDNA polymorphism with
longevity in Russian population
T. V. Zheykova 1 , M. V. Golubenko 1 , O. Y. Bychkova 1 , O. A. Makeeva 1 , S. V.
Buikin 1 , V. N. Maximov 2 , M. I. Voevoda 2 , V. P. Puzyrev 1 ;
1 Institute for Medical Genetics, Tomsk, Russian Federation, 2 Institute for Thera-