European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Genetic analysis, linkage, and association
show that the AA genotype means a 4-fold risk for the development of
RA (χ 2 =8.55, p=0.003, OR=3.81, 95%CI: 1.55-9.33). The data of the
study reported here provide direct evidence first in the literature, that
besides Crohn’s disease the IL23R 3’-UTR single nucleotide polymorphism
C2370A is an independent risk factor also for RA.
P1006. Genetic Association of TAPBP, IKBL, and MIF
Polymorphisms with Juvenile Rheumatoid Arthritis in Mexican
Population.
L. S. Orozco 1,2 , J. Ramirez 1,2 , R. Velazquez 1 , F. Espinoza 3 , G. Escamilla 3 , S.
Jimenez-Morales 1 , V. baca 4 ;
1 Instituto Nacional de Medicina Genómica, Mexico, Mexico, 2 Universidad
Autónoma de la Ciudad de Mexico, Mexico, Mexico, 3 Instituto Nacional de
Pediatria, Mexico, Mexico, 4 Hospital de Pediatria, Centro Medico Nacional, S.
XXI, Mexico, Mexico.
Juvenile rheumatoid arthritis (JRA) comprises the most common
chronic autoimmune arthropathies of childhood. Strong evidence is
emerging to suggest that the disease likely involves multiple susceptibility
genes, a feature common to many autoimmune disorders. Single
nucleotide polymorphisms (SNPs) in some genes of system immune
like TAPBP 260 C/G, IKBL - 62 T/A and MIF - 173 G/C, have been
found associated with ARJ in different populations,. Our aim was to
identify whether TAPBP, IKBL, and MIF polymorphisms are associated
with JRA in a sample of Mexican patients. We performed a case-control
association study in 133 pediatric patients with ARJ, and 350 unrelated,
healthy Mexican controls. Allelic discrimination was carried out by
TaqMan assay. The genotypes and allele frequencies were compared
between cases and controls by x2 test. Genotype frequencies were
in Hardy - Weinberg equilibrium. When genotype and allelic frequencies
were compared between cases and controls we observed that
the 260G TAPBP and - 173C MIF alleles ((p=0.01, OR 1.42, 95% CI
1.06- 1.89 and p=0.03, OR 1.4, 95% CI, 1.02 - 1.84, respectively) were
associated with susceptibility to JRA in Mexican population, while- 62
T/A IKBL (p= 0.01, OR 0.7, CI 95%, 0.52 - 0.93) was found associated
with protection.
P1007. Bone mass and genetic study of a 113 year-old man
M. Bustamante1,2 , L. Mellibovsky3 , X. Nogues3 , P. Lluch1 , A. Diez-Perez3 , D.
Grinberg1,2 , S. Balcells1,2 ;
1 2 Department of Genetics, UB, Barcelona, Spain, CIBERER, ISCIII, IBUB, Barcelona,
Spain, 3Hospital del Mar, URFOA, UAB, Barcelona, Spain.
Osteoporosis is a common disease that affects postmenopausal women
and elderly people. Aging induces loss of bone density and quality
resulting in a progressive incidence of fractures with significant morbidity
and mortality. The KLOTHO gene has been related to the ageing
process. Klotho knock-out mice display multiple disorders that resemble
human aging, including osteopenia. Furthermore, polymorphisms
in KLOTHO have been associated with life span and bone mineral
density (BMD). On the other hand, the LRP5 gene has been related
to variations in bone mass. In particular, the Gly171Val mutation has
been associated with a high bone mass phenotype (HBM).
Here we describe the bone mass and a limited exploratory genetic
study of a 113 year-old man and several first-degree relatives. No fractures
have been suffered by any of them and their BMD values are
listed in Table 1.
Regarding the KLOTHO gene, no mutation was detected in either the
index case or any of his relatives, with the exception of a previously
described polymorphic variant: one of the proband’s daughters presented
one copy of the KL-VS allele, which has been associated with
longevity and increased bone mass. Finally, mutation Gly171Val of the
LRP5 was not present in any individual. These data rule out these potential
genetic contributions. The identity of other longevity and/or high
bone mass genes or environmental factors remains to be defined.
Table 1 Values of bone mass in the index case and four relatives
BMD T-Score Z-Score
Individual Age
L2-L4 Femoral
neck
Total
hip
UD L2-
L4
Femoral
neck
L2-L4 Femoral
neck
Index
case
113 0.880 0.533 0.742 0.294 -3.00 -4.10 -1.45 -1.01
Daughter 77 1.033 0.768 0.914 0.335 -1.40 -1.80 -1.4 0.9
Daughter 81 0.939 0.731 0.853 0.251 -2.20 -2.10 0.28 0.0
Nephew 85 1.227 0.839 1.004 0.565 -0.10 -1.80 2.08 1.2
Brother 101 1.163 0.922 1.043 0.440 -0.60 -1.10 0.60 1.75
L2-L4: lumbar spine; UD: ultradistal radius
P1008. Focal Idiopathic Torsion Dystonia: A new locus identified
in a Large French family.
M. Y. Frederic 1,2 , C. Dhaenens 3,4 , C. Davin 1,2 , R. Mazzoleni 5,6 , A. Kreisler 5,6 ,
I. Vuillaume 3,4 , M. Martinez 7 , M. Claustres 1,8 , B. Sablonnière 3,4 , S. Tuffery-Giraud
1,2 , G. Collod-Beroud 1,2 , and the INSERM National Dystonia Network and
GIS Maladies Rares;
1 INSERM U 827, Montpellier, France, 2 Université Montpellier 1, Montpellier,
France, 3 CHRU de Lille, Institut de Biochimie et Biologie Moléculaire, Lille,
France, 4 INSERM U 837, Lille, France, 5 CHRU Lille, Pôle de Neurologie, Lille,
France, 6 Faculté de Médecine, Institut de Médecine Prédictive et de Recherche,
EA 2683, Lille, France, 7 INSERM U 563, Toulouse, France, 8 CHU Montpellier,
Hôpital Arnaud de Villeneuve, Laboratoire de Génétique Moléculaire,
Montpellier, France.
Focal Idiopathic Torsion Dystonia (FITD) is a group of movement disorders,
which is usually autosomal dominant with reduced penetrance.
Commonly described forms of FITD include cervical dystonia, blepharospasm,
oromandibular dystonia, laryngeal dystonia and limb dystonia.
We studied a large French family presenting with varied symptoms
of adult-onset FITD. The family is composed of 30 subjects (six definitely
affected and one asymptomatic obligate carrier). The average of
onset is 43 +/- 20 years. The three loci known to be implicated in FITD:
DYT6, DYT7 and DYT13 have been studied and excluded. Genomewide
linkage analyses have been performed with a parametric model
and incomplete age-dependant penetrance. This study identified a new
highly probable locus, DYTL, with several lod scores > +2 for contiguous
markers and a maximum of 2.37 (maximum lod score estimated
in the family: 2.62) defining a 40 cM candidate region. Concurrently,
another project has been established in collaboration with practitioners
implicated in the follow up of dystonic patients in France and associations
of patients to recruit other families presenting with FITD. Fortythree
families presenting with intrafamilial heterogeneous phenotypes
and corresponding to 170 affected patients have been identified and
are in recruitment. The preliminary results of the DYTL analysis in 14
families show possible segregation of this locus with the disease in ten
families and exclusion in 4 families. This last result further illustrates
the great genetic heterogeneity of FITD and is in favor of the existence
of more than one unassigned genes for this pathology.
P1009. Association of VEGF gene variant with left ventricular
hypertrophy in athletes
A. M. Hakimullina1 , E. V. Linde2 , I. I. Ahmetov1 , I. V. Astratenkova1 , V. A.
Rogozkin1 ;
1St Petersburg Research Institute of Physical Culture, St Petersburg, Russian
Federation, 2Combat Sports Academy, Moscow, Russian Federation.
Left ventricular hypertrophy (LVH) in endurance-oriented athletes is
generally understood to be a limiting factor for improving maximal
oxygen uptake (VO2max). Studies in related and unrelated individuals
clearly demonstrate that a high proportion of interindividual variability
in left ventricular mass and risk of LVH is attributable to genetic factors.
Vascular endothelial growth factor (VEGF) has been identified as
one of the key regulators of angiogenesis and, therefore, VO2max.
Several studies have shown that human VEGF gene polymorphisms
are associated with VEGF gene expression and VO2max before and
after aerobic exercise training. However, the influence of VEGF gene
variants on cardiac growth of athletes has not been examined. The
purpose of the study was to investigate the VEGF promoter G-634C
polymorphism for association with LVH in athletes. Seventy one Russian
athletes (all-round speed skaters and rowers) of national competitive
standard (sub-elite and elite) were studied. VEGF gene G-634C
polymorphism was determined by PCR-RLFP. Echocardiography was
performed for the measurement of left ventricular mass and function.
We found that left ventricular mass (LVM) and LVM index (LVMI) in
male sub-elite speed skaters was significantly greater in GG genotype
carriers than in heterozygotes (GC) (LVM: 333 (21) g vs. 254 (21) g,
p=0.002; LVMI: 169 (10) g/m2 vs. 130 (18) g/m2; p=0.015). It has been
shown previously that -634C allele is associated with increased VEGF
expression, and, therefore, can be considered to be protective against
LVH. Thus, VEGF G-634C polymorphism is associated with development
of LVH in athletes.
2