2009 Vienna - European Society of Human Genetics

Genetic analysis, linkage ans association
P17.33
Cardiac- and muscle-specific microRNAs miR-1, miR-133 and
miR-208 dysregulation in human myocardial infarction
E. Boštjančič1 , N. Zidar1 , D. Štajer2 , D. Glavač1 ;
1 2 Institute of Pathology, Ljubljana, Slovenia, Centre for Intensive Internal Medicine,
University Medical Centre, Ljubljana, Slovenia.
MicroRNAs (miRNAs) are small RNA molecules that regulate gene
expression in a variety of physiological functions, development and
disease. They are believed to be new promising therapeutic targets,
biomarkers and/or prognostic factors. From 866 human miRNAs described
so far, three miRNAs have been described as muscle and/or
cardiac specific: miR-1, miR-133, and miR-208, that contribute to heart
development and heart diseases. In animal model of myocardial infarction
(MI), to the best of our knowledge, there is only miR-1 expression
pattern analysed so far. We therefore analysed expression of miR-1,
miR-133a, miRNA-133b and miR-208 in human MI and fetal hearts in
comparison to the normal adult hearts. Autopsy samples of infarcted
heart tissue from 50 patients with MI were included, as well as heart
tissue from 8 healthy trauma victims and 8 fetuses that died in utero.
miRNAs expression was analysed using real-time PCR. miR-208 was
up-regulated in all cases of MI compared to healthy adults and fetuses.
Significant miR-208 up-regulation (~4-fold) was detected in MI
patients, indicating stress-induced up-regulation, and ~2-fold in MI patient
with ventricular fibrillation and/or tachycardia (VT/VF), indicating
its contribution to arrhythmogenesis. miR-1 and miR-133 expression
analysis suggested time-depended expression pattern in MI, whereas
all tested miRNAs were down-regulated in fetal in comparison to adult
hearts. In addition, some patterns of miR-1, miR-133a and miR-133b
expression in MI were similar in MI and fetal hearts supporting the concept
of reprogramming of cardiac genes in remodeling of the heart.
P17.34
The left ventricular systolic heart insufficiency in normotensive
cAD patients is associated with mtHFR 677tt genotype,
whereas in hypertensive APOE 33 subjects with mtHFR 1298cc
genotype
E. Strauss1 , W. Supinski2 , J. Gluszek3 , A. L. Pawlak1 ;
1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland,
2 3 Regional Hospital, Gorzow Wielkopolski, Poland, Department of Hypertension,
University of Medical Sciences, Poznan, Poland.
The methylenetetrahydrofolate reductase (MTHFR) 677C>T and
1298A>C genotypes, which influence homocysteine (tHcy) plasma
level, were studied for the possible specificity of involvement in development
of the left ventricular systolic insufficiency (LVSI) as late effect
of coronary artery disease (CAD).
A group of 190 men with CAD diagnosed by coronarography at age
t mutations: a case-control study and
meta-analysis
B. A. Jennings 1 , N. Khandanpour 2 , F. J. Meyer 2 , Y. K. Loke 1 , G. Willis 3 ;
1 UEA, Norwich, United Kingdom, 2 Department of vascular surgery, Norfolk
and Norwich University Hospital, Norwich, United Kingdom, 3 Department of
Molecular Genetics, Norfolk and Norwich University Hospital, Norwich, United
Kingdom.
Hyperhomocysteinaemia is associated with peripheral arterial disease
(PAD). Homocysteine metabolism is affected my multiple genetic, dietary
and other environmental factors.
This study considered the association of methylenetetrahydrofolate reductase
(MTHFR) 677C>T polymorphisms with the incidence of PAD
by performing a case-control study and a cross sectional study of homocysteine
levels. We recruited 133 patients with PAD in Norfolk (for
a folic acid intervention study, FOLCLAUD) and compared the MTHFR
allele distribution with 457 healthy individuals. We also carried out a
meta-analysis to place our data within the context of other published
studies. We searched Medline, Embase and Cochrane databases up
to March 2008 for any studies on the association between MTHFR
677C>T polymorphism and PAD.
The MTHFR 677C>T allele frequencies in the cases and controls were
0.37 and 0.33 and the odds ratios for the association of the 677 T allele
or TT genotype with PAD were 1.18 [95% C.I. 0.89, 1.58] and 1.99
[95% C.I. 1.09, 3.63]. Homozygotes for the MTHFR 677C>T mutation
had higher concentrations of plasma total homocysteine, odds ratio
2.82 [95% C.I. 1.03, 7.77] compared to wild types.
Twelve of 72 articles retrieved from the database search reported the
prevalence of mutations in PAD patients. A meta-analysis of 9 appropriate
studies, including our own, showed that being homozygous for
the C677T allele was associated with an increased risk of PAD; pooled
odds ratio 1.36 [95% C.I. 1.09, 1.68].
In conclusion, we have found a strong association between raised homocysteine,
the TT genotype and PAD.