2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
sol levels in persons reporting acute psychological stress .
Materials and methods: We studied 1,026 examinees from the Vis
island, Croatia . Standardised multilocus heterozygosity (sMLH) was
computed for each person from a genome-wide scan using 317 .000
single nucleotide polymorphisms . Morning cortisol level was measured
from the blood in all participants . Reported acute psychological stress
was measured using General Health Questionnaire 30 (GHQ-30) .
Results: GHQ-30 scores had a significant effect on the increase of
cortisol (pT) . None of these patients had a
diagnosis or family history of FD .
Conclusions
Overall, 1 .23% (95%CI: 0 .25-2 .21) of the patients in this cohort had a
recognised pathogenic GLA mutation . Despite having been described
as a polymorphic allele causing a pseudo-deficiency in plasma alphagalactosidase
activity, the role of p .D313Y in ISVCVD should be further
evaluated . The biologic relevance of the g .1136C>T 5’UTR mutation
requires supplementary investigation .
P07.063
Identification of Ile105Val polymorphism for GST-P1 gene in five
iranian ethnic groups: comparison with a mix-ethnic population
from tehran
F. Biramijamal 1 , M. Soltani 1 , S. Tanhaei 2 , M. Sheidai 2 , M. Sanati 1 ;
1 National Institute for Genetic Engineering & Biotechnology, Tehran, Islamic
Republic of Iran, 2 Shahid Beheshti University, Tehran, Islamic Republic of Iran.
The glutathione S-transferase P1 (GST-P1) protect cells from chemical
injury and has a function in detoxification of carcinogenic compounds
. The polymorphism at site of codon 105 in GST-P1 enzyme
has been described, this site lies in close proximity to substrate bind-
ing for electrophilic molecule . It is demonstrated that single nucleotide
polymorphisms (SNP) in various genes revealed a correlation between
the presence of specific allelic variants and cancer susceptibility in diverse
malignancies . Furthermore, it is shown that GST-P1 polymorphism
is involved in risk of development of different types of cancer . In
this study, we investigated the distribution of GST-P1 polymorphism,
at codon 105, among different Iranian populations . The samples were
collected from healthy population from five different ethnicity groups
(Fars, Mazandarani, Kurd, Turk and Turkmen) . We assessed the genotype
patterns of GST-P1 among Iranian ethnic groups in five regions.
Then, the data was compared with the allele distribution for above
gene among Tehran population (52 samples), a mix-ethnic population .
The GST-P1 genotypes, Ile105Val, were determined by polymerase
chain reaction-restriction fragment length polymorphisms (PCR-RFLP)
analysis in 269 Iranian healthy individuals . Allele frequency of GST-P1
genotype, Ile105Val, for above populations were similar, and there is
only significant difference among Fars and Turkmen populations.
P07.064
Contribution of environmental and genetic modifiers to severity
of the typical HFE-related haemochromatosis: a multivariate
analysis
G. Le Gac1 , V. Scotet2 , I. Gourlaouen1 , C. Thèze1 , B. Chanu1 , A. Mercier1 , M.
Mérour1 , C. Férec1,2 ;
1 2 Etablissement Français du Sang-Bretagne, Brest, France, Inserm U613,
Brest, France.
Background/aim: Expression of the common p .C282Y/p .C282Y HFErelated
haemochromatosis genotype depends on a balance between
accentuating and reducing factors . Some of these factors have been
identified, but they have mainly been analyzed independently. Here,
we aimed to determine contribution of different environmental and genetic
modifiers to total body iron overload.
Method: We studied 365 p .C282Y/p .C282Y patients (195 men and 170
women), and we used the iron removed by phlebotomy as quantitative
trait (log transformed). We tested the influence of age, gender,
alcohol abuse, body mass index, as well as six common variants: the
16189 T>C variant in mtDNA, the -308G>A variant in the TNF-alpha
promoter, the well known duplication of the haptoglobin gene (genotypes
Hp1-1, Hp1-2 and Hp2-2), and 3 SNPs located in genes involved
in regulation of hepcidin synthesis (BMP2 rs23756, BMP4 rs4901474
and HJV rs16827043) .
Results: Univariate analyses first highlighted the relation between each
potential modifiers and severity of the body iron overload. Factors with
a p-value lower than 25% were included in a same multiple linear regression
model . Then, stepwise elimination procedures were successively
performed until a model presenting only significant predictors
was found . Predictors of this last model were the male sex (p