2009 Vienna - European Society of Human Genetics

Evolutionary and population genetics, and Genetic epidemiology
Saint Quentin en Yvelines, Versailles, France, 5 Hôpital Tenon, Paris, France,
6 Faculté de médecine Cochin, Paris, France.
Identification of modifier genes and understanding their mechanism of
action represent two major challenges in human genetics. SAA1 is one
of the few modifiers identified in humans. This gene is known to influence
the risk of renal amyloidosis (RA) in patients with familial Mediterranean
fever (FMF), an autoinflammatory disorder associated with
mutations in MEFV. Indeed, the SAA1 alpha homozygous genotype
and the p.Met694Val homozygous genotype at the MEFV locus are
two main risk factors for RA. Here, we investigated Armenian FMF patients
and controls living in two neighboring countries: Armenia, where
RA is frequent (24%) and Karabakh, where RA is rare (2.5%). The frequencies
of p.Met694Val homozygotes were found to be similar in the
two groups of patients. However, a major deficit of SAA1 alpha homozygotes
was found in Karabakhian patients as compared to Armenian
patients (p=5.10 -5 ), whereas, in the two control populations, genotype
distributions at this locus were similar and complied with Hardy-Weinberg
equilibrium (HWE). Most importantly, we observed deviations
from HWE in the two groups of patients, and unexpectedly, in opposite
directions. A population-based study revealed that the excess of
SAA1alpha homozygotes in Armenian patients is readily explained by
the recruitment of patients with severe phenotypes. In contrast, the
deficit of alpha/alpha among Karabakhian patients revealed a negative
selection against individuals carrying this genotype. This study, which
provides new insights into the role of SAA1 in the pathophysiology of
FMF, represents the first example of deviations from HWE and selection
involving the modifier gene of a Mendelian disorder.
P10.56
Research of monogenic hereditary ophthalmopathology of the
Rostov region.
O. L. Kireeva, S. S. Amelina, O. V. Khlebnikova, R. A. Zinchenko;
Research Centre for Medical Genetics, Moscow, Russian Federation.
Hereditary pathology of the eye comes up to about 30% in the general
structure of eye disorders. Population of eight rural districts of the Rostov
region was examined. Total size of investigated populations was
320925 persons (90% Russians).The research was conducted under
the original examination protocol, providing for detection of more than
2500 various hereditary disorders (HD) and syndromes. The diagnostics
was performed by physicians of different specialties possessing
professional qualification of HD.
Families with monogenic herediritary ophthalmopathology (MHO)
which constituted 36,8% of the total number of patients identified in
this population. The prevalence of the whole MHO was 1:823 persons,
including isolated forms 1:1408, and the prevalence of 1:1981 as a
part of hereditary syndromes. Nosological spectrum of MHO in the
Rostov region is notable for a great variety. The most numerous MHO
groups were pathology of the retina, optic nerve and cataract. Virtually
all hereditary forms of retina degeneration known as of today were described
in the course of research, they make up 53% in the structure of
retina and optic nerve diseases. Another nosological form determining
a basic part of MHO burden in this population was autosomal dominant
and autosomal recessive cataracts with microcornea. MHO detected
in total was lower than in other rural populations of Russia.
P10.57
myeloperoxidase gene G-463A polymorphism in the
southeastern Anatolia
S. Budeyri1 , T. Sever1 , S. Pehlivan2 , V. N. Ulgezer1 , S. Oguzkan-Balci1 ;
1 2 University of Gaziantep, Gaziantep, Turkey, University of Gaziantep Faculty of
Medicine, Gaziantep, Turkey.
Myeloperoxidase (MPO) has been involved in the pathogenesis of several
diseases through excessive production of reactive oxygen species
(ROS) as well as through its genetic polymorphism.
The aim of this study was to determine Myeloperoxidase (MPO) gene
G-463A region polymorphism in healthy population of Southeastern
Anatolian region in Turkey. Also we compared the results according
to the literature data if there is any difference between the healthy
population of Southeastern Anatolian with the populations of different
countries.
The subjects of this study were 150 unrelated healthy individuals. The
genotyping was determined by polymerase chain reaction-restriction
fragment length polymorphism method.
The genotype distribution were observed in healthy population: 4.6%
in AA, 28.6% in AG and 66.6 % in GG. The frequency of A allele is 19
% whereas the frequency of G allele is 81 %.
The presence of the A and G allele frequencies in various populations
such as China, USA, Australia, Brazil, Europe, France and Germany
is similar to our results according to the published data. Nevertheless,
it was understood that A allele frequency in the populations in Taiwan
and Korea was lower than that of us while G allele frequency was
higher and that there was a deviation from Hardy-Weinberg Equilibrium
(p