2009 Vienna - European Society of Human Genetics

Genetic analysis, linkage ans association
Pompeu Fabra, Barcelona, Spain, 4 Institute of Inherited Metabolic Diseases,
Charles University – First Faculty of Medicine, Prague, Czech Republic, 5 Institute
of Biochemistry and Genetics, Ufa Science Center, Russian Academy
of Sciences, Bashkortostan, Russian Federation, 6 Centre of Cardiology, North
Estonia Medical Centre, Tallinn, Estonia.
Essential hypertension with its concurrent risk to other cardiovascular
diseases affects approximately 25% of population in industrialized societies.
Determining the genetic component of the disease is crucial for
better understanding of the molecular basis of the phenotype and for
developing more effective treatment of the disease.
I present the data on a novel, so far non-described human polymorphic
intronic AluYb8 element located in hypertension candidate gene
WNK1. WNK1 plays an important role in salt homeostasis through
different mechanisms and thereby has functional importance in blood
pressure regulation. Over-expression of the WNK1 gene is associated
with high blood pressure.
The comparative sequencing showed that the surrounding genomic
region of the human-specific WNK1 Alu insertion is highly conserved
between human and chimpanzee. Population genetic study targeting
the distribution of the Alu insertion in 22 human population samples
from Europe, Asia and Africa indicated an expansion of the Alu-bearing
chromosomes in Europe and Asia. The association between the
carrier status of the intronic AluYb8 element and blood pressure was
studied using 1211 untreated subjects from the HYPEST cohort (Estonian
population). Statistically significant association was detected
between the carrier status of the WNK1 AluYb8 and systolic as well as
diastolic blood pressure (linear regression testing, p= 0.01 and p=0.03,
respectively). Subjects with the Alu insertion had higher blood pressure
readings. Real-time PCR analysis showed that Alu insertion affects
the profile of alternative WNK1 transcripts.
In conclusion this study suggests a possible involvement of WNK1 intronic
polymorphic AluYb8 in increasing the susceptibility to essential
hypertension.
P17.30
Association Between Variants in the Genes for Leptin, Leptin
Receptor and Proopiomelanocortin with chronic Heart Failure in
the czech Population
A. Vasku1 , J. A. Bienertova Vasku2 , L. Spinarova3 , P. Bienert1 ;
1Masaryk University, Faculty of Medicine, Department of Pathological Physiology,
Brno, Czech Republic, 2Masaryk University, Brno, Czech Republic,
3Masaryk University, Faculty of Medicine, 1st Clinic of Internal Medicine and
Cardioangiology, Brno, Czech Republic.
Background: Patients with chronic heart failure (CHF) express enhanced
catabolic metabolism resulting in overall weight loss and adipokines
are generally recognized to play the crucial role in adipose
tissue signaling. The aim of this study was to investigate the possible
associations of defined variability in leptin (dbSNP ID rs7799039),
proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388)
and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate
their potential as the CHF susceptibility genes.
Methods: The case-control study comprised a total of 372 patients of
Caucasian origin with chronic heart failure (functional classes NYHA
II-IV, ejection fraction (EF) < 40%) and 407 healthy controls. The subjects
were genotyped for the LEP -2548 G/A, LEPR Gln223Arg and
POMC RsaI (5´-UTR) and C1032G variants (intron 1) by means of
PCR-based methodology.
Results: No case-control differences in genotypes or allele frequencies
as well as POMC haplotypes were observed between CHF patients
and controls. In multivariate regression modeling, the LEPR
Gln223Arg showed an independent prediction role for CHF, with the A
allele being more frequent in CHF under 56y of age (p=0.0002, OR =
1.29, 95% CI = 1.089 - 1.549).
Conclusions: Based on our findings, the RR genotype of LEPR Gln223Arg
polymorphism might be considered a genetic marker for earlier
CHF onset both in ischemic heart disease or dilated cardiomyopathy
patients. However, the role of the polymorphic variants in the
genes encoding for adipokines as potential CHF susceptibility genes
will require further investigation to elucidate the underlying pathophysiological
consequences.
P17.31
combined effect of the FABP2, PPARG2 and Pc1 gene
polymorhisms on the metabolic syndrome risk in a Romanian
population
K. Csep1 , G. Dudutz1 , M. Vitay2 , I. Pascanu1 , C. Banescu1 , L. Koranyi2 ;
1 2 University of Medicine and Pharmacy Tg Mures, Tg Mures, Romania, Drug
Research Center, Balatonfured, Hungary.
Objective. Based on the supposed multifactorial inheritance, we proposed
to follow the joint effect of three SNPs in candidate genes of the
metabolic syndrome. We have studied the risk of the disease diagnosed
according to the IDF reccommendations in the presence of the
FABP2-A54T, PPARG2-P12A and PC1-K121Q polymorphisms in the
population from Tg. Mures.
Material and methods. We carried out a case-control study on 144
patients and 73 healthy controls. Anthropometric measurements, biochemical
assays were undertaken, fasting insulinemia was measured
by ELISA, and insulin sensitivity was assessed by the QUICKI indices.
Genetic analysis was done by PCR followed by restriction enzyme digestion
with Hha I, BstU I and Ava II.
Results. Regardless of their type, the increase of the number of predisposing
alleles on the three studied loci associates with a significantly
increased risk to develop the syndrome (chi2 for trend = 7.99, df = 1, p
= 0.0047), and the risk was highest in the presence of the TT + PP/PA
+ QQ/KQ genotype combination (OR = 4.31, p= 0.015).
Conclusion. Our results confirm the small but additive effect of certain
predisposing gene polymorphisms as part of a polygenic system in the
development of the common metabolic syndrome, though individual
gene combinations can be presumed and other gene interactions like
epistasis seem also plausible.
P17.32
Polymorphic genetic markers are of significance in developing
of cardiovascular complications of the metabolic syndrome
A. N. Voitovich 1 , M. A. Bogdanova 1 , T. D. Glebovskaya 2 , B. I. Smirnov 3 , V. V.
Isakov 4 , S. I. Yagashkina 4 , O. N. Semenova 4 , N. N. Burova 2 , O. A. Berkovich 5 ,
E. V. Shliakhto 5 , V. I. Larionova 1 ;
1 St. Petersburg State Pediatric Medical Academy, Saint-Petersburg, Russian
Federation, 2 Federal heart, blood end endocrinology center after V.A. Almazov,
Saint-Petersburg, Russian Federation, 3 St. Petersburg State Electrotechnical
University, Saint-Petersburg, Russian Federation, 4 Research Center for People,
who lived in Blockaded Leningrad, Saint-Petersburg, Russian Federation, 5 St.
Petersburg Pavlov State Medical University, Saint-Petersburg, Russian Federation.
The metabolic syndrome (MS) is a cluster of metabolic abnormalities
often associated with development of various complications including
cardiovascular diseases. Recently, many studies showed some polymorphisms
in apolipoprotein genes might be associated with development
of cardiovascular complications of MS. OBJECTIVE: to study the
association of several polymorphisms in apo-genes APOA1 G-75A,
APOA1 C83T, APOC3 Sst1, APO E epsilon, APOA5 T-1131C, and
APOA5 S19W with MS complicated with acute coronary syndrome
(MS/ACS). STUDY POPULATION: MS/ACS patients, among them 76
males and 61 females (average age 61.7±1.0), and the controls, among
them 114 healthy males (average age 40.0±0.5) and 84 females (average
age 85.9±0.5) without any cardiovascular disease. All of them
were investigated clinically, biochemically and genetically. RESULTS:
Among male MS/ACS patients, there was a lower rate of carries of
APOE e4-allele compared to the controls (18% vs. 28%, OR=0.62,
90%CI 0.38-1.02, p=0.075). Also among them, there was a higher rate
of carries of APOA5 19W- allele compared to the controls (18% vs.
3%, OR=6.75, 95%CI 2.01-22.70, p