2009 Vienna - European Society of Human Genetics

Statistical genetics, includes Mapping, linkage and association methods
loproteinases is considered to be very important in the pathogenesis
of these diseases. Matrix metalloproteinase 9 (MMP-9) was shown to
be implicated in the pathogenesis of AAA and functional polymorphism
in the promoter region (-1562 C/T) of the MMP-9 gene was reported
to be associated with AAA in single report. The purpose of the present
study was to determine if there is an association between the MMP9
-1562 C/T genotype and susceptibility to abdominal aortic aneurysm or
aortoiliac occlusive disease in Polish patients.
Methods: Based on the PCR-RFLP analysis MMP9 genotypes were
determined in three selected groups: 182 patients with AAA and 205
patients with AIOD who underwent surgery; 200 healthy individuals
from control group. Genotypes were compared with demographic and
clinical data of subjects and analyzed in relation to risk factors.
Results: There were no significant differences in MMP9 -1562 C/T
genotype frequencies between AAA patients, AIOD patients and control
subjects.
Conclusion: No association of MMP9 -1562 C/T gene polymorphism
with abdominal aortic aneurysm or aortoiliac occlusive disease was
found.
P08.44
No association between myeloperoxidase G-463A polymorphism
and rheumatoid arthritis in turkish Patients
S. Pehlivan, A. Aydeniz, T. Sever, O. Altindag, S. Oguzkan-Balci, T. Harunlar;
Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
Myeloperoxidase (MPO) has been involved in the pathogenesis of
several diseases such as Rheumatoid Arthritis (RA) through excessive
production of reactive oxygen species (ROS) as well as through its
genetic polymorphism. We examined whether G-463A polymorphism
of Myeloperoxidase (MPO) gene was associated with RA.
Exactly, 75 patients with RA and 150 healthy control subjects were
included in this study. The genotyping was determined by polymerase
chain reaction-restriction fragment length polymorphism method. The
association between these SNP and RA was analyzed using chisquare
test and de-Finetti program.
MPOG-463A genotype distributions and allele frequency of RA patients
were not significantly different from healthy controls. In addition,
it was also determined that there was no deviation from Hardy-Weinberg
Equilibrium in any groups (p>0.05).
Whether there was an association between MPOG-463A gene polymorphism
and RA was investigated for the first time in this study in
literature and it was demonstrated that it did not exist in the Turkish
RA patients. It was planned to investigate the other polymorphisms of
MPO gene in the future.
P08.45
Folate pathway gene polymorphisms and development of
myopathyc process in PmD patients (moldavian population)
E. V. Scvortova 1,2 , V. C. Sacara 1 ;
1 Centre of reproductive health and medical genetics, Chisinau, Moldova, Republic
of, 2 University of Academy of Science, Chisinau, Moldova, Republic of.
Background:
During literature analysis we have found hypothesis that frequency of
MTHFR C677T mutation in it’s heterozygous state had a tendency to
increase due to it’s positive effect on some diseases, that lead to increased
survival of carriers. We set up that in Moldavian population,
PMD patients with different clinical features and severity of pathology
process. Main goal of present study was to determine if there is an
interaction between MTHFR polymorphism and development of myopathyc
process.
Materials and methods:
110 subjects were genotyped for the MTHFR 677 variants, among
them 55 patients with PMD and 55 age-matched healthy control subjects.
Blood samples were collected and DNA was isolated from peripheral
blood leukocytes. MTHFR variant alleles were determined by
a PCR-RFLP. Detection of the MTHFR C677T was performed according
original protocol with primers from Alpha DNA. Statistic analyze
was performed in SISA program.
Results:
We have found that MTHFR C677C allele presents among 38 (69.1%)
PMD and 22 (40.0%) controls (X 2 =9.39; p=0.002), the C677T genotype
among 11 (20.0%) PMD, 24 (43.6%) controls (X 2 =7.08; p=0.007),
and the T677T allelic variant was observed 6 (10.9%) PMD, 9 (16.4 %)
controls (X 2 =0.695; p=0.405).
Conclusions:
Mathematic analyze of obtained data demonstrates statistically significant
differences between PMD and control MTHFR genotypes.
Frequency of MTHFR C677T was higher in control group. Whereas
in PMD patients more often MTHFR C677C allelic variant. This study
needs to be continued with MTHFR A1298C, MTRR A66G and MTR
A2756G allelic variants for learning compound effect.
P08.46
Genetic heterogeneity of multiple self-Healing squamous
Epithelioma in a tunisian family not linked to chromosome 9
(9q22.3-q31)
O. Mamaï 1 , M. Gribaa 1 , L. Bouzouffara 2 , L. Adala 1 , I. Ben Charfeddine 1 , T. Ben
Lazreg 1 , A. Mili 1 , M. Denguezli 2 , A. Saad 1 ;
1 Laboratoire de Cytogénétique, de Génétique moléculaire et de Biologie de
la, Sousse, Tunisia, 2 Service de Dermatologie et de Vénérologie. CHU Farhat
HACHED. Sousse, Sousse, Tunisia.
Multiple self-healing squamous epithelioma (MSSE), also known as
Ferguson-Smith Disease, is a rare genodermatosis with an autosomal
dominant inheritance. Affected patients suffer from recurrent skin
lesions, which clinically and histologically resemble to keratoacanthomas
or well-differentiated squamous cell carcinomas, but with a
spontaneous regression, leaving only atrophic scars. This disease has
been linked to 9q22.3-31 locus between D9S197 and D9S1809 markers.
This region has a size of 4 cM (2.05 Mb).
Here we investigate a five generation Tunisian family in which 7 members
are affected by MSSE. A detailed disease history with particular
attention to the age of onset, distribution, and clinical course of their
skin lesions were noted and a full clinical examination was performed
for every patient. Haplotype analysis, using six polymorphic short tandem
repeat markers in 9q22.3-31 locus, doesn’t find any commune
haplotype segregating with MSSE in this family. So that proposes the
existence of at least one other locus linked with this disease and suggests
its genetic heterogeneity feature.
P08.47
A novel syndromic neuro-ichthyosis maps to chromosome
Xq22-24
T. Pippucci 1 , P. Magini 1 , M. Vargiolu 1 , D. Turchetti 1 , C. Graziano 1 , E. Pompilii 1 ,
E. Malaspina 2 , L. Mazzanti 3 , R. Bergamaschi 3 , G. Pilu 4 , G. Cenacchi 5 , E. Franzoni
2 , G. Romeo 1 , M. Seri 1 ;
1 Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, U.O. Genetica
Medica, Bologna, Italy, 2 Neuropsichiatria Infantile, Policlinico Sant’Orsola-
Malpighi, Bologna, Italy, 3 Ambulatorio di Auxologia, Sindromologia e Sindromi
Rare, Policlinico Sant’Orsola-Malpighi, Bologna, Italy, 4 Medicina dell’età prenatale,
Policlinico Sant’Orsola-Malpighi, Bologna, Italy, 5 Anatomia e Istologia,
Policlinico Sant’Orsola-Malpighi, Bologna, Italy.
The term neuro-ichthyosis refers to a clinically and genetically heterogeneous
group of syndromes in which ichthyosis can be found in association
with various neurological disorders, spanning from mental retardation
to spasticity, epilepsy, polyneuritis and pyramidal tract signs.
These syndromes are very rare; despite of the fact that they could
cluster into families, many still lack a locus assignment. For some of
the forms for which a locus has been recognized, the disease gene has
been identified. The mode of inheritance could be either autosomal or
X-linked, dominant or recessive. Generally, X-linked ichthyosis is due
to steroid sulfatase deficiency, which is determined by deletions of the
STS gene on chromosome Xp22. Here, genetic mapping of a novel
form of X-linked ichthyosis undue to STS deficiency is reported. We
performed an X chromosome linkage analysis with 31 markers on 16
DNA samples. A clinical picture of ichthyosis, agenesia of corpus callosum
(ACC), microcephalia, seizures, mental retardation and spastic
tetraparesis characterized the proband and his 1st degree cousin died
at age 6. Intriguingly, mother of this latter child interrupted a second
pregnancy in the second trimester, and phoetus showed clear hyperkeratosis
and complete ACC. The two affected males and the fetus
inherited the same haplotype on chromosome Xq22-24; multipoint
linkage analysis yielded LOD scores of 2.06 in this region, containing
230 genes. An array-CGH scan on the proband at a 20 kb resolution
demonstrated that no copy number variations occurred. Mutational
screening of the Xq22-24 genes expressed in skin is in progress.