2009 Vienna - European Society of Human Genetics

Complex traits and polygenic disorders
P09.065
A study of Kashin-Beck Disease in the homogeneous population
of tibet in china
R. S. Gunasekera 1,2 , J. Cokenour 1 , P. Sen 3 , D. Heath 4 , M. Han 5 ;
1 University of Houston-Victoria, Victoria, TX, United States, 2 Humanitarian Solutions,
Inc., Pearland, TX, United States, 3 Baylor College of Medicine, Houston,
TX, United States, 4 Innovative Humanitarian Solutions, Inc., Pearland, TX,
United States, 5 ProHealth Physicians, Manchester, CT, United States.
Kashin-Beck disease (KBD) is an osteoarthropathy which manifests in
children marked by dramatically low levels of serum selenium, iodine,
bone and joint deformity, and limited mobility. The disease is endemic
to rural Tibet, China; North Korea, and Siberia. Early investigations had
led to the hypothesis that the disease was due to dietary factors, due
to deficiencies in certain essential nutrients in high plateaus. However,
supplementation of the deficient trace minerals conducted by others
has had no positive effect on affected persons. Our group has begun
investigations to the possibility that genetic elements may also be
involved with possible environmental effects in-utero. Pedigree studies
were conducted on 200 individuals in nuclear families with clinical
symptoms. Patients observed ranged from 6 to more than 60 years.
KBD was diagnosed when an affected person had persistent pain,
restricted mobility, or deformity of the knees, ankles, elbows, wrist, interphalangeal
joints, hips, or shoulders, in the absence of trauma. Preliminary
analysis suggests KBD having an autosomal recessive pattern
of inheritance in most families with a possible higher penetrance in
women. Occurrence of the disease exhibits familial aggregation while
suggesting the form of inheritance polygenetic, and due to multifactorial
factors. Initial studies further suggests that deficiencies in selenium
and iodine may not be causal, but markers of an underlying condition
of extreme oxidative stress brought on by reactive oxygen species
acting to inhibit proper mesenchymal cell and bone development by
apoptosis. This study attempts to describe pedigree investigations and
nutritional genomics of the disease.
P09.066
Association of the AcE and BDKRB2 gene polymorphisms with
physical performance of kayakers
E. B. Akimov, I. I. Ahmetov, D. V. Rebrikov, A. G. Tonevitsky;
All-Russian Research Institute of Physical Culture and Sports, Moscow, Russian
Federation.
Circulating angiotensin I converting enzyme (ACE) exerts a tonic regulatory
function in circulatory homeostasis, through the synthesis of vasoconstrictor
angiotensin II, which also drives aldosterone synthesis,
and the degradation of vasodilator kinins. A polymorphism in intron 16
of the human ACE gene has been identified in which the presence (I allele)
rather than the absence (D allele) of a 287 bp Alu-sequence insertion
fragment is associated with lower serum and tissue ACE activity.
Bradykinin is a potent endothelium-dependent vasodilator and acts via
the bradykinin B2 receptor (encoded by BDKRB2). The absence (-9),
rather than the presence (+9), of a 9 bp repeat sequence in exon 1 has
previously been shown to be associated with increased gene transcription
and higher BDKRB2 mRNA expression. The aim of the study was
to find interrelation between ACE and BDKRB2 gene polymorphisms
and physical performance of elite Russian kayakers. Genotyping was
performed by RT-PCR. Physiological parameters were evaluated by
Kayak Ergometer and MetaLyzer II Gas Analyzer at the beginning and
at the end of preparation period. Maximal oxygen consumption was
increased by 12.7% and 14.8% in males and females, respectively.
Furthermore, the ventilation volume (VE) was decreased by 9.6% in
males. The total number of ACE I and BDKRB2 -9 alleles, favorable for
endurance performance, was negatively correlated with VE values in
males (p=0.0074) and females (p=0.017), indicating that these alleles
are associated with the improvement of work economization of respiratory
muscles (one of the indicators of aerobic capacity).
P09.067
European Lactase Persistence Allele is Associated With
increase in Body mass index
J. A. Kettunen 1,2 , K. Silander 2,3 , O. Saarela 3 , V. Anttila 1 , J. Laitinen 4 , A. Hartikainen
5 , A. Pouta 5,6 , P. Lahermo 2 , S. Männistö 3 , A. Jula 7 , J. Virtamo 3 , V. Salomaa
3 , G. Davey Smith 8 , M. I. McCarthy 9,10 , M. Järvelin 11,12 , M. Perola 13,3 , L.
Peltonen 1,2 ;
1 Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 2 FIMM, Institute
for Molecular Medicine, Helsinki, Finland, 3 National Institute for Health and
Welfare, Department of Chronic Disease Prevention, Helsinki, Finland, 4 Finnish
National Institute of Occupational Health, Oulu, Finland, 5 Department of Clinical
Sciences/ Obstetrics and Gynecology, Oulu, Finland, 6 National Public Health
Institute and University of Oulu, Oulu, Finland, 7 Department of Health and
Functional Capacity, National Public Health Institute, Helsinki, Finland, 8 MRC
Centre of Causal Analyses in Translational Epidemiology, University of Bristol,
Bristol, United Kingdom, 9 Oxford Centre for Diabetes, Endocrinology and Metabolism,
Oxford, United Kingdom, 10 The Wellcome Trust Centre for Human
Genetics, Oxford, United Kingdom, 11 Department of Epidemiology and Public
Health, Imperial College London, London, United Kingdom, 12 Institute of Health
Sciences, University of Oulu, Oulu, Finland, 13 FIMM, Institute for Molecular
Medicine Finland, Helsinki, Finland.
The global prevalence of obesity, usually indexed by body mass index
(BMI) cut-offs, has increased significantly in the recent decades,
mainly due to positive energy balance. However, the impact of a selection
for specific genes cannot be excluded. Here we have tested the
association between BMI and one of the best known genetic variants
showing strong selective pressure: the functional variant in the cisregulatory
element of the lactase gene. We tested this variant since it
is presumed to provide nutritional advantage in specific physical and
cultural environments. We found that the variant responsible for lactase
persistence among Europeans was also associated with higher
BMI in a Nordic population sample (p = 1.3*10 -5 ) of 15 209 individuals,
the size of the effect being close to that of FTO. We tested the effect
of population stratification and concluded that the association was not
due to population substructure.
P09.068
Association between copy number variation of glycogen
synthase kinase 3 beta / Nr1i2 and major depression
Z. Elek 1 , E. Szantai 1 , R. Nagy 1 , G. Faludi 2 , A. Sarosi 2 , M. Sasvari-Szekely 1 ;
1 Department of Medical Chemistry, Molecular Biology and Pathobiochemistry,
Semmelweis University, Budapest, Hungary, 2 Department of Clinical and
Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University,
Budapest, Hungary.
Copy number variation (CNV) or copy number polymorphism (CNP) is
a novel approach in candidate gene studies. Recently, glycogen synthase
kinase 3 beta (Gsk3β) and its adjacent gene, Nr1i2 (pregnane X
receptor isoform) has been reported to associate with bipolar depression
(Lachman et al, 2007. Here we present a case - control study
of 216 patients with major depression and 175 controls, involving the
chromosomal region of glycogen synthase kinase 3 beta (Gsk3β) and
its adjacent genes, Nr1i2 and C3ORF15. The gene dosage has been
measured by Taqman (Applied Biosystems) real time PCR systems,
as well as by conventional PCR and capillary electrophoresis. In accordance
with the previously published results, the variations in the
copy number of the above genes seem to be very rare, although an
accumulation of increased copy number has been found in the patient
group (4/216 vs. 1/175). On the other hand we did not find any deletion
of these genes in our samples. Taking together the published results of
Lachman et al. and ours, amplification of this region seems to have a
significant (p=0.006) increase among patients with major depression.
P09.069
Significant associations between AKT1 SNP markers and Major
Depressive Disorder in the chinese population
Z. Z. Zhao1 , X. Q. Chen2 , D. Q. Li1 , M. J. Wang1 , M. Ai1 , N. Chen2 , J. M. Chen1 ,
X. M. Li1 , L. Kuang1 ;
1The First Affiliated Hospital, Chongqing Medical University, Chongqing, China,
2West China Hospital, West China Medical School, Sichuan University, Chengdu,
China.
Background: V-akt murine thymoma viral oncogene homologue 1
(AKT1) is a serine/threonine kinase. Abnormality of AKT1 is involved
in various diseases, including mental disorder. Recent evidence suggests
that the Variation in AKT1 gene has been associated with schizophrenia,
Parkinson’s disease and type II diabetes. But the relationship
of AKT1 gene variation in depression is unknown. The aim of the
present study was to investigate the potential role of variability within
AKT1 gene polymorphisms as a risk factor for major depressive disorder
(MDD).
Method: We performed a case-control association analysis of AKT1.
Five single nucleotide polymorphisms (SNPs) according to the origi-