2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
lence of CVD risk mutations in São Miguel Island (Azores) . From this
population, 87 healthy individuals were analysed for the following variants:
factor V Leiden, MTHFR (C677T and A1298C) by PCR-RFLP,
and prothrombin by real-time PCR (FACTOR II Q - PCR Alert Kit,
Nanogen Advanced Diagnostics) . The allelic and genotypic frequencies
of these polymorphisms were estimated and their values were
compared with other populations . The results demonstrate that values
of the mutant alleles MTHFR 677T (38 .5%) and 1298C (23 .6%) were
relatively similar to those found in other populations . However, in São
Miguel Island population, factor V Leiden shows a value of 1 .7% for
the 1691A allele, one of the lowest in Europe . Whereas, prothrombin
(20210A) is present at a frequency of 3 .4%, being one of the highest .
Genotype frequencies of the genetic polymorphisms analysed showed
similar values to other European populations . Furthermore, thirteen
genetic profiles were identified in the study group: 13 individuals
(14 .94%) had none of the variants, 37 (42 .53%) only one, 33 (37 .93%)
two, and 4 (4 .60%) had three or more polymorphisms . The joint analysis
of these polymorphisms represent a valuable contribution to further
understanding the CVD in São Miguel Island . Funded by Azorean Government
(M1 .2 .1 ./I/003/2005) . lmotavieira@hdes .pt
P06.045
Analysis of sequence variants and splice isoforms in iL18RAP in
celiac disease
G. Trynka 1 , A. Zhernakova 2 , K. A. Hunt 3 , G. A. R. Heap 3 , L. Franke 2 , J. Romanos
1 , A. Szperl 1 , M. Bruinenberg 1 , M. C. Wapenaar 1 , P. Deloukas 4 , R. McManus
5 , D. A. van Heel 3 , C. Wijmenga 1,2 ;
1 University Medical Center Groningen, Groningen, Netherlands, 2 University
Medical Center Utrecht, Utrecht, Netherlands, 3 Queen Mary University of London,
London, United Kingdom, 4 Wellcome Trust Sanger Institute, Cambridge,
United Kingdom, 5 Trinity Centre for Health Science, Dublin, Ireland.
Celiac disease (CD) is a common autoimmune disorder of the small intestine
induced by the ingestion of gluten protein in genetically susceptible
individuals . CD is a complex genetic trait in which presence of the
HLA-DQ2/8 genotype is necessary but not sufficient for the disease
development . Previously a genome wide association study (GWAS) in
the UK celiac cohort initially identified a new non-HLA locus on chromosome
4q27 . In a more extensive follow-up study, 1020 UKGWAS top
associated SNPs were independently genotyped in three additional
European celiac cohorts (2 .410 celiac cases, 4 .828 controls) and seven
novel celiac loci were identified. One of the associated regions (P
overall=8 .49x10 -10 ) maps to a 350-kb block on the chromosome 2q11-
2q12 . This block contains four genes including two IL-18 receptors
(IL18R1 and IL18RAP) . The strong correlation between the IL18RAP
mRNA expression and associated SNP was observed in a group of
treated celiac patients (pG) was observed
in a single control and the other one (c .1384+70_1384+71insT)
was found in two celiac individuals . We are now genotyping the 19
SNPs in a large cohort of Dutch, UK and Irish celiac samples . IL18RAP
is known to express two splice variants . Using quantitative real-time
PCR we are currently testing for correlation between the genotypes
and the expression of IL18RAP splice isoforms .
P06.046
Relationship between Beta (3) integrin (itGB3) Leo 33 Pro
Polymorphizm and cerebral infarction
S. K. N. Lee E.Y, S. K. N. Lee E.Y;
Medical Institution, Almaty, Kazakhstan.
Objective: To explore the distribution of B beta 3 integrin (ITGB3) polymorphism
in Kazakh population and the association of the polymorphisms
with the occurrence of different types cerebral infarction .
Methods: The B beta 3 integrin - Leu 33 Pro polymorphism was identified
by polymerase chain reaction and restriction fragment length polymorphism
in 37 patients with different cerebral infarctions (CI) and 87
healthy controls matching on age and sex . .
Result : Distribution of genotypes ITGB3 basic group ( LL 37,8%, LP
56,8%, PP 5,4%),in control group (LL 55,2%, LP 44,8%) (p=0,2880) .
Frequency 33Pro allele provided of above that control group (33, 8%
and 22, 4% accordingly) (p 80 years)
without CAD (group V), all originated from Saint-Petersburg, Russia .
Genotypes were determined by PCR-RFLP, statistic: χ 2 tests, SPSS .
In group I levels of total cholesterol, LDL-CH and triglycerides was
significantly higher, and levels of HDL-CH lower in comparison with
group II. We found that frequency of B1B2 genotype was significantly
higher among patients from group I than among patients from group II
and group III (p=0,02 and p=0,04 respectively; OR=2) . There was no
difference in B1 and B2 allele frequency in droups of CAD and healthy
men .Our results allow to suggest that B1B2 genotype of CEPT is a risk
factor of CAD in men but not in women in analyzed groups .