2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
P06.049
Analysis of cFtR gene in italian patients with idiopathic
normocalciuric calcium nephrolithiasis
M. Gabaldo 1 , C. Bombieri 1 , A. Fabris 2 , A. Lupo 2 , P. F. Pignatti 1 , G. Gambaro 2 ;
1 Section of Biology and Genetics, Dpt.of Mother and Child and of Biology-Genetics,
University of Verona, Italy, 2 Division of Nephrology, Dpt.of Biomedical-
Surgical Sciences, University Hospital of Verona, Italy.
Idiopathic calcium nephrolithiasis (ICN) is a multifactorial disease,
whose pathogenesis involves a complex interaction of environmental
and individual factors, possibly genetic . A growing body of evidence
shows an association between Cystic Fibrosis (CF) and calcium nephrolithiasis
. Of patients with CF, 3 .0 to 6 .3% are affected with nephrolithiasis,
generally with calcium oxalate stones, a percentage greater
than that of age-matched healthy controls (1-2%) . CFTR mutations
may be responsible for abnormal kidney development or may affect
some steps of renal crystallization processes, thus favouring stone formation
. Aim of this project was to investigate whether idiopathic normocalciuric
calcium renal stone formers are associated with CFTR gene
mutations or polymorphisms . A group of 44 italian normocalciuric ICN
patients and presenting no story reminding of CF were selected . Clinical
and laboratory test to determine renal function were performed to
exclude other causes of nephrolitiasis . The complete coding sequence
and the intronic flanking regions of the CFTR gene were analysed by
DGGE and sequencing . A total of 5/44(11%) patients had a mutation in
the CFTR gene, all in heterozygosis (2 F508del, 1 D1152H, 1 R110H, 1
R75Q) . This results is not statistically different from that found in a previous
study on the general population (HumGenet,106:172-178,2000) .
The frequency of other common polymorphisms of the CFTR gene is
also not different from the general population . These results show that
the CFTR gene carrier status is not a risk factor for normocalciuric
ICN .
Work supported by Italian Cystic Fibrosis Research Foundation (grant
FFC#6/2004) with contribution of “Fondazione G .Zanotto Verona” .
P06.050
MTHFR gene polymorphisms as a risk factor for congenital heart
disease in são miguel island, Azores (Portugal)
R. Cabral 1,2 , F. Tejero 1 , L. de Fez 1 , P. R. Pacheco 1,2 , C. C. Branco 1,2 , C. P. Duarte
3 , R. Anjos 4 , L. Mota-Vieira 1,2 ;
1 Mol Genetics & Pathology Unit; Hospital of Divino Espirito Santo of Ponta
Delgada, EPE, Azores, Portugal, 2 Instituto Gulbenkian de Ciencia, Oeiras,
Portugal, 3 Pediatric Department; Hospital of Divino Espirito Santo of Ponta
Delgada, EPE, Azores, Portugal, 4 Pediatric Cardiology Department; Hospital of
Santa Cruz, Carnaxide, Portugal.
Congenital heart defects (CHD) are among the most common birth
defects worldwide, occurring in São Miguel Island with a prevalence
of 9 .16 per 1000 live births (Cymbron T et al . Community Genet; 9:
107-112, 2006) . Several studies demonstrate that the intake, by the
mothers, of periconceptional folic acid reduces the risk of congenital
anomalies, including CHD . This fact led to the search of candidate
genes involved in folate metabolic pathways . Methylenetetrahydrofolate
reductase (MTHFR), a regulating enzyme of this metabolism, is
responsible for the availability of active folate . Our main goal is to test
the C677T and A1298C MTHFR polymorphisms as risk factor for CHD .
We analyzed these two variants in a control population of 469 healthy
blood donors from São Miguel and in the CHD group of 95 patients . For
677CC, 677CT and 677TT, we observed 28 (29 .5%), 54 (56 .8%), and
13 (13 .7%) CHD cases, respectively . Similar proportions were found
in the control individuals, that is, 162 (34 .5%) were CC, 223 (47 .6%)
were CT and 84 (17 .9%) were TT . Genotype frequencies of 1298AA,
1298AC and 1298CC were 56 (58 .9%), 38 (40%) and 1 (1 .1%) among
cases and 264 (56 .3%), 177 (37 .7%) and 28 (6%) among control population,
respectively. These values reveal no significant differences
between both groups (odds ratio, 95% confidence interval). Because
we have evidences of familial aggregation in CHD cases, this study is
being concluded with the transmission/disequilibrium test in order to
analyse the transmission distortion in the 89 nuclear families . Funded
by Azorean Government (M1 .2 .1 ./I/003/2005) . ritacabral@hdes .pt
P06.051
Peripheral Gene Expression Profiling of CCK-4-Induced Panic in
Healthy subjects
K. Kallassalu 1,2 , E. Maron 3,4 , A. Tammiste 1 , R. Kolde 5 , I. Tõru 4 , V. Vasar 4 , J.
Shlik 6 , A. Metspalu 7,2 ;
1 IMCB, Tartu, Estonia, 2 Estonian Biocentre, Tartu, Estonia, 3 Research Department
of Mental Health, The North Estonian Regional Hospital, Psychiatry Clinic,
Tallinn, Estonia, 4 Department of Psychiatry, University of Tartu, Tartu, Estonia,
5 Institute of Computer Science, University of Tartu, Tartu, Estonia, 6 Department
of Psychiatry, University of Ottawa, Ottawa, ON, Canada, 7 University of Tartu,
Tartu, Estonia.
Panic attacks are anxiety-related phenomena defined as discrete periods
of abruptly escalating intense fear or discomfort with multiple
somatic and cognitive symptoms . Panic-induction or challenge tests
in healthy subjects provide certain advantages in the investigation
of genetic mechanisms of panic . Understanding why some, but not
all, healthy subjects demonstrate panic response to a challenge test
may advance knowledge about the pathogenesis of panic attacks and
panic disorder .
In the present study we used the Illumina Human-6 v2 Beadchips for
whole genome expression profiling in healthy subjects (n=31) participating
in a cholecystokinin-tetrapeptide (CCK-4) challenge test . We
aimed to explore the association between gene expression signatures,
the occurrence of panic attacks, and the influence of the CCK-4 challenge
on peripheral transcriptional activity .
The results showed that, after summarizing gene expression profiles
before and after CCK-4 provocation, 16 genes were differently expressed
between panickers and non-panickers (p