2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
bolic genes are probably involved in PCOS pathogenesis .
The aim of our study was to investigate whether there is a correlation
between variants of genes: IRS-1, IGF-2, SHBG, INS and symptoms
of PCOS in Polish patients .
Up-to-date 64 PCOS patients (diagnosed on the basis of criteria mentioned
above) and 37 health controls were enrolled to our study .
We focused on four polymorphisms G972R (IRS-1), ApaI-rs680A/
G (IGF-2), TAAAAn (SHBG ) and VNTR classI/III (INS) tagged by -
23HphI-rs689 A/T .
Our results indicate that:
- prevalence of 972R variant is higher in PCOS group
- allel A of ApaI is less frequent in the patient group compared with
controls . On the contrary genotype A/A is more prevalent in patients
group .
- VNTR classI/III distribution in both groups is nearly the same, whereas
class III alleles homozygotes are more frequent among PCOS patients
- TAAAAn - any association with neither PCOS nor its severity was
found .
Our preliminary studies indicate, in consistent with literature, that variants
of genes (IRS-1, IGF-2, INS) can be among the factors involved
in PCOS pathogenesis . Nevertheless further analysis on larger cohort
is performed .
Supported by KBN2P05E11729
P06.231
Linking Genetic Susceptibility with clinical findings: a case
study in periodontitis
V. Moustakis 1,2 , G. Potamias 1 , M. Laine 3 , B. Loos 3 , L. Koumakis 1 ;
1 Institute of Computer Science, FORTH, Heraklion, Greece, 2 Dept. of Production
Engineering and Management, Technical University of Crete, Chania,
Greece, 3 Dept. of Oral Microbiology and Dept. of Periodontology, Academic
Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands.
Diagnosis and hypothesis formation in clinical decision making (CDM)
involves the integration of patient history, clinical and laboratory findings
. Patient history incorporates genotypic information and carries genetic
susceptibility towards disease manifestation . We present a hybrid
multi-stage computational model which, in the first stage assesses a
genetic susceptibility index (GSI) towards disease, in the second stage
links GSI with phenotypic (clinical and laboratory) parameters and in
the third stage generates comprehensible knowledge patterns that tie
together genotypic and phenotypic information sources . The model integrates
two inductive machine learning methods, namely: association
rule mining (ARM) and decision tree learning (DTL) with behavioral
communication theory . ARM is used to support formation of genotypic
patterns which, are taken through a behavioral communication theory
model to establish GSI both at the genotype and phenotype levels .
DTL is included at the third stage to validate learned knowledge .
The model is demonstrated by means of a case study on periodontitis .
Data are drawn from the warehouse of ACTA and incorporate genotypic
and phenotypic data . Genotypic data include single nucleotide
polymorphisms (SNP) and origin and clinical data include microbial
values, life style habits, and age . The application of the model on the
abovementioned data validates the proposed approach .
Presentation is cast in topic “Genetic analysis, linkage, and association”
and documents a generic procedure, which can be used in any
endeavor aimed at genotype - phenotypic data and knowledge integration
.
Work reported was partially supported via the INFOBIOMED NoE, and
to be also used in the GEN2PHEN European project .
P06.232
The GATC project: identification of novel genetic markers of
cisplatin induced hearing-loss in children
H. Katzov-Eckert 1,2 , C. J. D. Ross 1,2 , H. Visscher 1,2 , C. Hildebrand 3 , M. Dube 4 ,
R. S. Rassekh 3 , P. Rogers 3 , M. S. Phillips 4 , B. C. Carleton 2,3 , M. R. Hayden 1,2 ;
1 Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada,
2 University of British Columbia, Vancouver, BC, Canada, 3 Children’s and
Women’s Health Centre of B.C., Vancouver, BC, Canada, 4 University of Montreal,
Montreal, QC, Canada.
Adverse drug reactions (ADRs) are potentially life-threatening responses
to medications . Children are at greater risk for ADRs, because
>75% of approved drugs used in children are untested in pediat-
ric populations . Adverse drug reactions in pediatric oncology regimens
are especially severe and account for 22% of all pediatric oncology
hospital admissions . Cisplatin is one of the most effective anti-cancer
agents for the treatment of solid tumors . However, a major dose-limiting
toxicity of cisplatin is severe, permanent hearing loss . In previous
studies the risk of developing cisplatin ototoxicity was increased with
younger age and higher cumulative dose, but the contribution of genetic
risk factors remains undetermined . We aimed to evaluate genetic
markers predictive of hearing loss in children treated with cisplatin .
DNA samples and detailed clinical information from cisplatin induced
hearing-loss cases (n = 60) and drug-matched controls (n = 44) were
collected through the GATC nation-wide ADR surveillance network .
DNA samples were genotyped for a panel of 3072 single nucleotide
polymorphisms (SNPs) in 220 genes. A significant genetic association
with increased hearing loss risk was found for patients carrying variants
in a key drug metabolizing enzyme (P-value=0.0001; OR=infinity).
In addition, variants in known drug transporters were also associated
with cislatin ototoxicity (P