2009 Vienna - European Society of Human Genetics

Genetic analysis, linkage ans association 0
P17.41
study for association between the polymorphism t/c of the
gene cYP17 promoter and the risk of premature coronary artery
disease
C. Agiannitopoulos1 , H. Kasparian2 , V. Votteas2 , K. Lamnissou1 ;
1 2 Department of Biology, University of Athens, Athens, Greece, Department of
Cardiology, “Laiko” Hospital, Athens, Greece.
Objective: It is well documented that sex hormones influence the risk
of developing cardiovascular disease. Several genes are involved in
the synthesis of sex hormones. The CYP17 gene encodes the enzyme
cytochrome P450c17α which functions at key steps in the production
of human sex steroid hormones. A T/C polymorphism in the 5’ promoter
region of the CYP17 gene has been described. In the present study,
we investigated the possible association between the T/C polymorphism
of the promoter of CYP17 gene on risk of premature coronary
artery disease (CAD) in the Greek population.
Methods:A total of 180 CAD patients, documented by coronary angiography,
aged less than 58 years and 120 healthy controls were studied.
To genotype the subjects we used the PCR-RFLP method.
Results: The frequencies of GG, GC, CC genotypes were 0.43, 0.38,
0.19, respectively, in the patient group and 0.32, 0.47, 0.21, respectively,
in the control group. The frequencies of T and C alleles were
0.62 and 0.38 in the patient group and 0.55 and 0.45 in the control
group. The data between the two groups were analyzed by chi-square
test. Our results showed that there are no patient/control significant
differences.
Conclusion: The results of this study suggest that there is no association
of the T/C promoter polymorphism of the CYP17 gene with the risk
of premature coronary artery disease. Thus, this polymorphism may
not be used as genetic marker for CAD risk assessment.
P17.42
Analysis of GcKR and ApoA5 genes in Hungarian patients with
ischemic stroke
L. Járomi 1 , V. Csöngei 1 , E. Sáfrány 1 , B. Faragó 1 , L. Magyari 1 , K. Horvatovich 1 ,
A. Maász 1 , C. Sipeky 1 , Z. Szolnoki 2 , B. Melegh 1 ;
1 Department of Medical Genetics and Child Development, University of Pécs,
Pécs, Hungary, 2 Department of Neurology and Neurophysiology, Pándy Kálmán
County Hospital, Gyula, Hungary.
The development of ischemic stroke is caused by both environmental
factors - especially triglyceride level increase - and complex genetic
predisposition. Recently, several studies confirmed the role of Glucokinase-hexokinase
4-regulator (GCKR) gene in triglyceride accumulation
in patients with coronary artery diseases. The aim of our study
was to investigate the genetic association between ApoA5, GCKR
gene polymorphisms and the possible changes of triglyceride level in
Hungarian ischemic stroke patients. The genotype of the 513 Caucasian
patients (207 males, 306 females; mean age: 65.1±0.62) stratified
into three subgroups (“small-vessel occlusion type”, “large-vessel
group” and “mixed group”) and 172 controls (49 males, 123 females;
mean age: 56.5±1.20) was determined by PCR-RFLP methods. The
T-1131C, IVS3+G476A and C56G variants in ApoA5 gene increased
significantly the level of triglyceride, and associated with higher risk
for the development for stroke disease. By contrast, in the case of
T1259C in ApoA5 gene and the two polymorphisms of GCKR gene
(rs1260326, rs780094) we could not detect significant differences between
the stroke patients and the control subjects. In conclusion, we
observed a significant association between the disease and elevated
triglyceride levels in the presence of three variants of ApoA5 gene, but
no correlation was found for the two polymorphisms of the GCKR gene
in the Hungarian ischemic stroke population.
P17.43
Variations in the glucokinase gene and its receptor are
simultaneously associated with higher fasting glucose and
lower triglyceride
M. Sotos-Prieto 1,2 , M. Guillen 1,2 , P. Guillem-Saiz 1,2 , O. Portoles 1,2 , D. Corella 1,3 ;
1 CIBER Fisiopatología de la Obesidad y Nutrición, Valencia, Spain, 2 Departement
of Preventive Medicine, Valencia, Spain, 3 Departement of Preventive
Medicine, Valencia, Austria.
The Glucokinase gene (GCK) is a regulator of glucose storage and
disposal in the liver and its activity is modulated by binding to glu-
cokinase regulatory protein (GCKR). Studies from genome-wide association
(GWA) have identified the SNP rs1260326 at the GCKR
gene as a genetic marker for triglyceride concentrations. Moreover,
the SNP rs1799884 at the GCK gene has been associated with increased
type 2 diabetes risk (DT2) and lower TG concentrations.
However, the effects of these genetic variants in the Mediterranean
population remain to be investigated. Therefore, our aim was to analyze
the effects of GCKR rs1260326 (P446L) and the GCK rs1799884
-30G>A on fasting triglycerides and DT2 in a high cardiovascular risk
Mediterranean population. We studied 945 subjects (340 men and 605
women) with high cardiovascular risk (age: 67+/-6 years) recruited
in Valencia, Spain. The genotypic frequencies of GCKR rs1260326
were 29.8%CC, 51%CT, 19.3%TT, and 64.9%GG; 32.2% GA, 2.9%
AA for GCK rs1799884. The TT homozygous had significantly higher
triglycerides (CC: 111.4; CT: 124.22; TT: 126.23 mg/dl; p= 0.026) and
a borderline lower fasting glucose (p=0.060). However, homozygous
subjects (AA) for the promoter SNP had higher plasma glucose and
lower triglyceride. Furthermore, the GCK -30AA was significantly associated
with increased DT2 risk (adjusted OR: 2.05 [CI: 1.25-3.38];
p=0.005) and the GCKR TT with higher hypertriglyceridemia risk (adjusted
OR: 1.39 [CI: 1.11-1.74]; p=0.005). Conclusion: GCKR and the
GCK genetic polymorphisms are significant determinants of triglyceride
concentration and fasting glucose in a high cardiovascular risk
Mediterranean population.
P17.44
PPAR-alpha gene polymorphism correlates with lipid and
glucose levels, physical activity and body mass index in
children from families with history of cardio-vascular disease.
A. Y. Vasina, A. P. Khmyrova, O. A. Kononova, L. O. Lubashova, T. S. Razorenova,
V. V. Masalova, N. V. Slizovsky, M. D. Didur, V. I. Larionova;
St.Petersburg State Pediatric Medical Academy, Saint-Petersburg, Russian
Federation.
BACKGROUND: Children whose parents suffered from cardiovascular
disease (CVD) have hypoalphacholesterolemia quite often. Alpha
cholesterol levels are regulated by PPAR-alpha. It is well known that
HDL cholesterol concentration is regulated by physical activity concentration.
OBJECTIVES: To study an association between PPAR-alpha
gene polymorphism and lipid and glucose levels, physical activity and
body mass index (BMI) in children from families with a history of CVD.
STUDY POPULATION: 58 children (average age 13.2±0.53) and adolescents
with family history of CVD. METHODS: We have evaluated
physical activity index per week and per day. Lipid spectrum in all
patients was determined by enzyme-linked immunoassay. In all patients
we detected glucose concentration and BMI. Molecular testing of
PPAR-alpha gene polymorphism (L162V) was performed by PCR. RE-
SULTS: Among 58 children and adolescents, 53 of them had LL-genotype
and 5 had LV-genotype. Frequency of L-allele and V-allele were
estimated to be 0.96 and 0.04, respectively. In children carried LV-genotype,
we detected a higher level of cholesterol (5.08±0.08, 4.82±0.13
mmol/l) and lower triglycerides level (0.84±0.04 vs 1.49±0.116 mmol/l)
compared to children with LL-genotype. We determined correlations
between cholesterol and LDL level (r=0.82) in children with LL-genotype
and between physical activity intensivity and glucose level (r=-
0.84) in children with LV-genotype. Also we have found a correlation
between BMI and glucose level (r=0.82) and between HDL and LDL
levels (r=-0.98) in children with LV-genotype. CONCLUSION: children
from families with history of CVD carried LV-genotype need both an
intensive physical activity and their lipid and glucose levels to be controlled.
P17.45
combined genetic variants 6A/6A of MMP- and i/i of ACE have a
strong preventive evidence in patients with dilatative pathology
of ascending thoracic aorta
G. Sinkunaite 1 , A. Tamosiunas 2 , M. Jonikas 1 , R. Benetis 3 , V. Lesauskaite 1 ;
1 Laboratory of Molecular Cardiology, Institute of Cardiology, Kaunas University
of Medicine, Kaunas, Lithuania, 2 Department of Preventive Medicine, Institute
of Cardiology, Kaunas University of Medicine, Kaunas, Lithuania, 3 Department
of Cardiac, Thoracic and Vascular Surgery, Kaunas University of Medicine,
Kaunas, Lithuania.
Numerous studies have proved impact of genotypes 5A/5A of MMP-3
and D/D of ACE for cardiovascular diseases development. We have