2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
our normotensive control group were similar to these detected in other
Caucasian populations . The genotype distribution of this polymorphism
did not show statistically significant differences between the two
explored groups (p=0 .822) . The comparison of the groups, divided by
gender, also did not demonstrate significant differences in the genotype
and allele distribution (p>0 .05) .
Conclusion: Our study does not support the involvement of the -
344C>T polymorphism of CYP11B2 gene in the susceptibility to hypertension
in Bulgarian patients . Due the small sample size, however,
further studies in larger groups are warranted .
P06.135
increased frequency of the iVs4+39c>t allele of PGHD-15 gene
in group of patients with severe course of iBD
A. Nelke-Lozynska 1 , M. Podralska 2 , T. Banasiewicz 1 , R. Slomski 2 , W. Meisner 1 ,
E. Czkwanianc 3 , I. kubinska 3 , P. Krokowicz 1 , A. Plawski 2 ;
1 Karol Marcinkowski University of Medical Sciences, Poznan, Poland, 2 Instytitute
of Human Genetics, Poznan, Poland, 3 Department of Pediatrics and Gastroenterology,
Institute of Polish Mother’s Memorial Hospital, Lodz, Poland.
Inflammatory bowel diseases (IBD) are autoimmunological disorders
(MIM #266600) with genetic background, characterized by chronic
inflammation of the wall of gastrointestinal tract. IBD include two clinical
entities: Crohn’s disease and ulcerative colitis (MIM#191390) . The
incidence of these diseases in Western population ranges from 100
to 300 per 100 000 . The symptoms of Crohn’s disease may arise in
any part of gastrointestinal tract, however most often the distal portion
of the ileum and caecum is affect. Inflammatory process penetrates
through the whole thickness of the bowel wall and skip lesions are
typical. Continuous inflammatory lesions confined only to colonic and
rectal mucosa are characteristic for ulcerative colitis . Fistulas are absent
and the inflammation never adopts the granulomatous form.
In our research we examined the frequency of alleles in the NOD2
gene and 15-@hydroxyprostaglandin dehydrogenase gene (PGDH-
15) in 58 patients with severe postoperative relapses of inflammatory
bowel diseases, 27 children with inflammatory bowel diseases and in
control group (100 persons) . The average age of onset was 31 years
in the group of patients with severe disease course and 11 in the group
of children . We observed the elevated frequency of the alleles 3019-
3020insC and 802C>T of the NOD2 gene in comparison to the control
group . The allele IVS4+39C>T of the PGDH-15 gene in the group of
ill with the heavy course occurred two times more frequent than in the
control group and three times more frequent in comparison with the
group of affected children .
Project was financed by MNiSzW 2P05A06929
P06.136
mmP1 G-1607GG and mmP9 c-1562t gene variants in idiopathic
bronchiectasis
M. Stankovic 1 , A. Nikolic 1 , A. Divac 1 , L. Rakicevic 1 , A. Tomovic 2 , N. Petrovic-
Stanojevic 3 , M. Andjelic 3 , V. Dopudja-Pantic 3 , M. Mitic-Milikic 4 , L. Nagorni-Obradovic
4 , D. Radojkovic 1 ;
1 Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia,
2 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland,
3 Zvezdara University Medical Center, Belgrade, Serbia, 4 Institute for Tuberculosis
and Lung Disease, University Clinical Centar of Serbia, Belgrade, Serbia.
Bronchiectasis is a chronic infective and inflammatory disease characterized
by dilatation of bronchi and sputum production . Although the
pathogenesis of bronchiectasis is not fully undersood, destruction of
the bronchial wall that contributes to the development of airway dilatation
may result from excessive extracellular matrix degradation . Matrix
metalloproteinases (MMPs) are a family of proteolytic enzymes, which
play an essential role in tissue remodeling and repair . Genetic variants
of genes involved in extracellular matrix remodeling may drive the
pathological processes that could lead to the development of bronchiectasis
. The aim of this study was to analyse MMP1 G-1607GG and
MMP9 C-1562T promotor polymorphisms in development of idiopathic
bronchiectasis .
The genotypes of 37 patients with idiopathic bronchiectasis and 102
controls were determined by conformation sensitive gel electrophoresis
for MMP1 G-1607GG gene variant and PCR-RFLP for MMP9
C-1562T polymorphism .
The distribution of -1607GG allele was significantly higher in patient
group (p=0 .014) . Heterozygote carriers of -1607GG allele had a 5 .3-
fold increased risk for bronchiectasis development (62 .2% vs. 50%,
p=0 .013) . The OR was even greater (8 .7) for homozygous -1607GG
genotype (29 .7% vs. 18 .6%, p=0 .006) compared with homozygotes
for 1G allele .
The MMP9 C-1562T allelic and genotype frequencies did not show
significant differences between the groups.
According to our results MMP1 -1607GG variant might be involved in
pathogenesis of idiopathic bronchiectasis . This polymorphism is associated
with higher gene expression and may influence lung parenchyma
damage and subsequent bronchial wall destruction and development
of airway dilatation .
P06.137
Novel differentiating genetic markers for cD and Uc
Y. A. Nasykhova 1 , N. V. Semenov 2 , A. G. Kharitonov 2 , T. E. Ivashchenko 1 ;
1 Ott’s Institute of Obstetrics & Gynecology, St-Petersburg, Russian Federation,
2 Medical Academy of Postgraduate Study, St-Petersburg, Russian Federation.
CD and UC belong to the inflammatory bowel diseases (IBD) with heterogeneous
clinical manifestations, genetic factors and response to
treatment . That provides increased interest for detection of differentiating
factors valuable for precise early diagnostics of these diseases .
Five polymorphic variants of two genes (Gly908Arg, Arg702Trp, Leu-
1007fins of NOD2/CARD15 gene and -308G/A, -238G/A of TNFA
gene) were studied in CD patients (n=102), in UC patients (n=71) and
also in control group (n=100) . The frequency of -308A allele of the
TNFA gene was increased in both groups of patients with CD and UC
as compared to controls (15%, 11% and 4%, respectively) . We have
found an extremely significant difference for Leu1007fins, mutation of
NOD2/CARD15 gene which results in truncated protein . This mutation
was revealed in 15% of patients with CD and only in 2% of patients
with UC (p=0 .0055) . In control group the frequency of this mutation
was 3% . The frequencies of carriers of two others genetic variants
(Gly908Arg, Arg702Trp) were lower in UC patients (4% and 1%) as
compared to these ones in CD patients (8% and 6%) but it was not
significant.
Thus that mutation Leu1007fins of gene NOD2/CARD15 plays a crutical
role in pathogenesis of Crohn’s disease and might be treated as
a differentiation marker between patients with CD and UC . Consequently
that may improve diagnostics of these diseases and provide
appropriate treatment .
P06.138
Associations of CARD , DLG , OCTN , TLR , IL , IL 0 and
TNFα genes variants with Inflammatory Bowel Disease
O. A. Schagina1 , P. V. Shumilov2 , A. A. Polyakov1 ;
1 2 Research Centre for Medical Genetics, Moscov, Russian Federation, Russian
Government Medical University, Moscov, Russian Federation.
Inflammatory bowel disease (IBD) is a multifactorial polygenic disease
with probable genetic heterogeneity . It is characterized by chronic inflammation
of the gastrointestinal tract.
64 unrelated patients from 6 to 14 years old with IBD and 52 controls
children were investigated . The aim of our research was searching
association between IBD and nine polymorphous variants of seven
genes . The analysis for CARD15 R702W, G908R, Leu1007fs, DLG5
R30Q, OCTN1 L530F, TLR4 D2999G, IL10 c .-1082 g>a, TNFα c .-308
g>a variants, and IL1 VNTR polymorphism was performed by means
of MLPA and AFLP analysis .
Results of genotyping are presenting in the table .
Thus it is not revealed associations between carriage of the variant
alleles these genes and Inflamatory Bowel Disease at Russian children
.
Allele frequencies of the minor alleles (%)
gene CARD15 CARD15 CARD15 DLG5 OCTN1 TLR4 IL1 IL10 TNFa
allele 702W 908R c .3020 insC 30Q 503F 299G 574 c .-1082a c .-308a
IBD group 2,3 3,9 5,5 5,5 46,7 15,3 4,7 0,8 7,0
Control group 2,9 2,9 4,0 5,9 39,6 11,7 0 0 9,7
Fisher exact test (P) 1,00 1,00 0,76 1,00 0,43 0,65 0,16 1,00 0,57