2008 Barcelona - European Society of Human Genetics

Normal variation, population genetics, genetic epidemiology
Methods: To investigate possible biologic gender differences in normal
α-galactosidase activity, plasma and leukocyte enzyme activities were
determined in eight male and nine female healthy unrelated Caucasian
young adults . All subjects had been genotyped and carried the
standard genomic sequence for the 5’ untranslated region of the α-galactosidase
gene, a region that may contain single nucleotide polymorphisms
affecting the level of gene expression . Differences in gender
means were compared by the independent samples t-test .
Results: The mean (±SD) α-galactosidase activity levels were 28.7
(±3.7) and 27.5 (±4.7) μkat/Kg in leukocytes (p=0.57) whereas mean
plasma activities±SD were 2 .2 (±0 .5) and 2 .9 (±0 .7) nkat/L (p=0 .03),
respectively for males and females .
Conclusion: There seems to be a gender difference in normal plasma
α-galactosidase activity. This finding, if confirmed in a larger sample,
may have to be taken into account in the definition of normal laboratory
reference ranges and may warrant a reassessment of the sensitivity of
the plasma α-galactosidase assay for the identification of females with
Fabry disease . We hypothesize that a higher fractional post-translational
sialylation of the newly synthesized enzyme in the female Golgi
apparatus may contribute to this difference .
P07.009
Familial amyloid polyneuropathy (AttR V30m): a change in
paradigm?
A. Sousa 1,2 , A. M. Silva 3 , L. Maia 3 , T. Coelho 3 ;
1 ICBAS (Instituto Ciências Biomédicas Abel Salazar), U.P., Porto, Portugal,
2 IBMC (Instituto Biologia Molecular e Celular), U.P, Porto, Portugal, 3 Unidade
Clínica de Paramiloidose, HGSA (Hospital Geral Santo Antonio), Porto, Portugal.
Andrade first described FAP (1952) as a disease occurring between
25 and 35 yrs . He reported 64 patients, 13 of which had no family
history of the disease . Later PE Becker established its AD mode of
inheritance and interpreted isolated cases not as a de novo mutation
but as the expression of incomplete penetrance of the gene in one of
the parents. This hypothesis could only be tested after the finding of
the mutation in 1985 .
Our aims were: 1) to estimate the number of probands with no affected
parent at time of diagnosis; 2) to study age at onset of proband and its
changes over time . Between 1939 and 2005, 2075 patients (525 families)
were diagnosed at HGSA. Families were classified as “new” when
the proband reported no similar disease in earlier generations .
Age-at-onset varied from 20-80 yrs (mean 37 .1 in women, 32 .4 in
men) . 209 probands (40%) had no affected parent at time of diagnosis
. This type of family represented 68% of those diagnosed in last
decade (only 27% before 1985) . Mean age-at-onset of probands of
“new” families was 46 .0 yrs (vs. 32 .3 yrs for “classical” families) and it
has increased over time, being 49 .5 yrs in last decade .
Regarding FAP two realities coexist in Portugal: families with several
generations of affected (where probands have “classical” onset) and
probands with late-onset who report no similar disease in previous
generations . The mutation may cross generations without clinical manifestations,
then expresses as late-onset and later anticipation occurs .
P07.010
the ß 2 -adrenergic receptor gene polymorphism and arterial
hypertension in children
S. V. Kuzmina 1 , M. A. Bogdanova 2 , O. S. Romashkina 2 , O. A. Mutafyan 1 , V. I.
Larionova 2 ;
1 St.Petersburg State Medical Academy of Postgraduate Studies, Saint-Petersburg,
Russian Federation, 2 St.Petersburg State Pediatric Medical Academy,
Saint-Petersburg, Russian Federation.
The ß 2 -adrenergic receptor (ADRB2) is thought to be associated with
arterial hypertension (AH) and its altered function can results in increased
blood pressure (BP) . Q/E27 polymorphism of ADRB2 gene is
considered functionally important .
Though some reports indicate that polymorphism in the ADRB2gene
is associated with essential hypertension, its role in BP levels remains
unclear .
The aim of this study were to investigate distribution of ADRB2 genotypes
and allele frequencies of Q/E27 polymorphism in hypertensive
and normotensive children and to compare clinical systolic BP levels
between carriers of the different genotypes .
84 children with systolic AH (aged 7-17) and 90 normotensive children
(aged 7-17) were include the study .
Arterial hypertension was defined as systolic/diastolic blood pressure
measurements higher than 95 age-gender-height percentile of the adopted
reference values .
DNA was extracted from blood samples according to standard protocols
. The Q/E27 polymorphism was genotyped by using the PCR
restriction fragment length polymorphism analysis .
The distribution of ADRB2 genotypes and allele frequencies did not
differ significantly between patients with AH and control subjects.
Clinical systolic BP in patients with QQ- genotype was 133,65±11,5
mm Hg, QE-genotype was 133,43±8,4 mm Hg, EE- genotype was
132,52±7,5 mm Hg . Clinical systolic BP differences among genotypes
were not found .
The allelic and genotypic frequencies of the Q/E27 polymorphism in
hypertensive and control subject
Q/E27 Hypertensive (n=84) Control (n=90) p
QQ 17 (20,2%) 14 (15,6%) 0,722
QE 46 (54,8%) 52 (57,8%)
EE 21 (25,0%) 24 (26,7%)
Q 80 (47,6%) 80 (44,4%) 0,5527
E 88 (52,4%) 100 (55,6%)
P07.011
iL4 genetic polymorphisms contribution to madeira population
risk of asthma
A. G. Berenguer1 , R. Câmara2 , A. T. G. Fernandes1 , S. Oliveira2 , A. Brehm1 ;
1 2 Human Genetics Laboratory, Funchal, Portugal, Imunoallergology Unit, Central
Hospital of Funchal, Funchal, Portugal.
The allergic disease prevalence is influenced by both environmental
exposure and the population’s genetic predisposition to the disease .
Five different polymorphisms of previously associated genes to some
of asthma’s phenotypic characteristics namely IL4RP2 and IL4-590
(C/T) at 5q31-32; ADRB2 16A/G at 5q31-32; ADAM33 S1 (G/A) and
ADAM33 V4 (C/G) at 20p13 were studied in 28 asthmatic children
with positive skin prick test to house dust mite from affected sib-pair
families composed by two children and their biological parents . Allele
frequencies from asthmatic patients were then compared to a sample
from Madeira general population . Both genotypic and allelic frequencies
as well as comparisons between both groups were accessed by
ARLEQUIN 3 .1 .
We have found significant differences regarding both IL4RP2 and IL4-
590 (C/T) polymorphisms between the two groups (p