2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
The duplicated region of the PKD1 gene was amplified by long range
polymerase chain reaction (PCR) followed by nested PCR . Mutation
screening was performed using denaturing gradient gel electrophoresis
(DGGE), heteroduplex analysis (HA) and high-resolution melting
(HRM) . Suspected samples were then sequenced .
In the PKD1 gene we detected 30 germline mutations among 90 unrelated
individuals; 24 mutations unique for Czech population . We identified
11 nonsense mutations, 13 missense mutations, 3 frameshifting
mutations, 2 deletion in-frame and 1 mutation in splice site . In the
PKD1 gene we detected great numbers of different polymorphisms or
unclassified variants.
Establishment of localisation and type of mutations and their genotype
- phenotype correlation in ADPKD families will improve DNA diagnosis
and could help to assess the clinical prognosis of ADPKD patients .
Supported by grant projects IGA MZ CR NR/9427-3, VZ MSMT
0021620806
P06.235
the association of metabotropic glutamate receptor subtype 8
(mGluR8) polymorphism with executive attention
J. V. Schegolkova, V. A. Shleptsova, A. G. Tonevitsky;
Moscow State University, Moscow, Russian Federation.
The glutamatergic signaling pathway represents candidate susceptibility
system involved in mechanism of forming attention and working
capacity . One of attractive candidate for study of molecular physiology
of attention is metabotropic glutamate receptor subtype 8 (mGluR8) .
Expression of mGluR8 was observed in the olfactory system, the neocortex,
the limbic cortex including the hippocampus and the amygdala .
Electron microscopically, mGluR8 was largely observed on the axon
terminals . Especially in several regions of the hippocampus it was
found in the active zone of both asymmetrical and symmetrical synapses
where mGluR8 may regulate glutamate release as an autoreceptor
or GABA release heterosynaptically .
Influence of mGluR8 polymorphism located 29 bp after the termination
codon (2756C/T) on executive attention was conducted on volunteers
. 108 students of Moscow State University (mean age 20±2, girls
= 61, boys = 47) were tested by Schulte tables. We found significant
association of mGluR8 polymorphism with executive attention only in
males . Carriers of T allele (TT,CT) implemented the test faster than CC
group (p=0,02) .
P06.236
Q192R and L55m polymorphism of PON1 in patients with
coronary heart disease (cHD) of different age and sex.
G. D. Pardo Perales 1 , M. A. Bogdanova 2 , A. N. Voitovich 2 , O. S. Romashkina 2 ,
O. A. Bercovich 3 , S. I. Yagashkina 4 , O. N. Semenova 4 , V. A. Isakov 2 , O. A.
Berkovich 5 , H. B. Kirillova 1 , V. I. Larionova 2 ;
1 St. Petersburg State Chemical Pharmaceutical Academy, Saint-Petersburg,
Russian Federation, 2 St. Petersburg State Pediatric Medical Academy, Saint-
Petersburg, Russian Federation, 3 St. Petersburg Electrotechnical University,
Russia, Saint-Petersburg, Russian Federation, 4 Research Center for people
who lived in blockaded Leningrad, Saint-Petersburg, Russian Federation, 5 St.
Petersburg State Medical University, Saint-Petersburg, Russian Federation.
Paraoxonase-1, a high-density lipoprotein-associated enzyme, is
believed to protect low-density lipoproteins from oxidation and thus
decrease the risk of CHD . The aim of this study was to investigate if
paraoxonase-1 gene (PON1) Q192R and L55M polymorphisms influence
the risk of CHD . 597 patients (438 men and 159 women) were
included in our study: 227 men who survived myocardial infarction (MI)
under the age of 45 (group I), 96 men with MI after 60 years (group II)
and 115 healthy men (group III); 75 angiographicaly diagnosed CHD
women (group IV) and 84 women without CHD (group V) . All patients
originated from Saint-Petersburg, Russia . Genotypes were determined
by PCR-RFLP, paraoxonase activities were measured spectrophotometrically
and standard enzymatic methods were used to determine
levels of total cholesterol, triglycerides and HDL cholesterol on a spectrum
analyzer. Statistical significance of differences between groups
was assessed with χ 2 -test . We found that in group IV the frequency
of 55M allele of PON1 was a statistically higher comparing to group V
(p=0,029). In group I amount of QR patients were significantly higher
comparing to group IV (p=0,003) . In group II amount of QQ patients
were significantly lower comparing to group IV (p=0,009). There were
no any differences in allele or genotype frequencies distributions be-
tween the groups of CHD men . Our results suggest that both Q192R
and L55M PON1 polymorphisms play the role in risk of CHD . Furthermore,
PON1 polymorphisms act in various ways in patients of different
age and sex .
P06.237
the associations between PON1 55mm genotype and coronary
artery disease and between the low HDL/LDL ratio values and
the large arteries diseases
E. Strauss 1 , K. Waliszewski 2 , W. Supinski 3 , J. Gluszek 2 , W. Majewski 2 , M.
Swierczek 1 , M. Juszczak 1 , A. L. Pawlak 1 ;
1 Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland,
2 Medical University, Poznan, Poland, 3 Regional Hospital, Gorzow Wkp, Poland.
The differences in the vascular diseases risk factor profiles, depending
on the localization of the arterial diseases were analyzed in the series
of 428 patients with coronary artery disease (CAD), 210 patients with
aortoiliac occlusive disease (AIOD) and 255 cases of abdominal aortic
aneurysm (AAA) - total 893 of vascular disease patients, as well as
in 262 persons without symptoms of vascular disease . The SNPs of
the genes related to the homocysteine metabolism: MTHFR 677 C>T,
PON1-108C>T, L55M; as well as the lipoprotein profiles were analyzed
in search for the functional differences predisposing either to the CAD
or to the diseases of the large arteries . The SNPs were determined by
PCR-RLFP methods .
In CAD group frequency of PON1 55MM genotypes (16,6%) was
about 1,7-fold higher as compared to this either in AIOD+AAA group
(10,8%, p