2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
to the identification of deleterious variants that could be responsible for
AUT or SCZ in our patients . We are currently performing functional
validation of these variants using animal models (zebrafish, fruitfly,
worm or mice neurons).
P06.036
Association between polymorphisms of immune defense
modifier genes and autoimmune diseases in Tomsk population
A. A. Rudko1 , E. I. Kondratieva2 , N. V. Tarasenko2 , E. V. Loshkhova2 , G. N.
Yankina2 , N. P. Stepanenko2 , V. P. Puzyrev1 ;
1 2 Research Institute of Medical Genetics, Tomsk, Russian Federation, Siberian
State Medical University, Tomsk, Russian Federation.
The results of an investigation of the influence of immune defense
modifier genes polymorphism [IL1B (+3953A1/A2), IL1RN (VNTR), IL4
(3 ′ -UTR G/C), IL4RA (I50V), IL12B (A1188C) and VDR (F/f and B/b)]
on the development and presentation of type 1 diabetes, celiac disease
(CD), and autoimmune thyroiditis (AT) are presented . The study
was performed in 49 families with 139 patients affected by CD, 110
families with 350 type 1 diabetes patients, 119 patients with AT, and
129 unaffected controls of Russian ethnicity from Tomsk . We discovered
various potential associations. The first was between +3953A1/
A2*IL1B and type 1 diabetes (p=0 .040), and the second between the
VV genotype of I50V*IL4RA and AT (p=0 .032) . Family-based studies
revealed association between 3’-UTR G/C* IL4 and CD (p=0 .024), and
between I50V*IL4RA with type 1 diabetes (p=0 .018), and additionally
with complications of the disease: diabetic retinopathy (p=0 .050), nephropathy
(p=0 .026) and neuropathy (p=0 .050) . Furthermore, the association
with clinical course of the CD (typical form) was obtained
for I50V*IL4RA and F/f*VDR polymorphisms (p=0 .001 and p=0 .009,
respectively) . The combination of type 1 diabetes and AT was associated
with allele A2 of the VNTR*IL1RN polymorphism (p=0 .018),
whereas combination of CD and AT was associated with allele C of
G/C 3’-UTR*IL4 . Thus, in this investigation we detected associations
of the studied phenotypes mainly occurred in polymorphic variants of
the Th2-immunity genes .
P06.037
Genetic analysis of pedigrees with autosomal dominant
Premature Graying of hair
S. Ari 1 , A. K. Maiti 2 , J. V. Solanki 3 , R. Uppala 1 , U. Radhakrishna 1 ;
1 Green Cross Blood Bank & Genetic Centre, Ahmedabad, India, 2 Sealy Center
for Molecular Medicine, University of Texas Medical Branch, Galveston, TX,
United States, 3 Department of Animal Genetics & Breeding, Veterinary College,
Gujarat Agriculture University, Anand-388001, India.
Whiteness of hair is one of the most recognizable early signs of aging .
This is also termed ‘Canities’ . It is caused by the gradual decrease of
pigmentation that occurs when melanin ceases to be produced in the
hair root, and new hairs grow without pigment . The change naturally
occurs as people age, usually turning hair from its natural color to gray,
then to white . Premature-graying of hair (MIM 139100) or whiteness of
the hair is a phenotypic change that appears as early as at teens and
twenties, for some, even in childhood . The causes of this relatively
common condition are largely unknown, although genetic, medical and
other environmental factors all are suspected . The phenotype is frequently
associated with many known genetic disorders such as Book
syndrome, Waardenburg syndrome and Lison syndrome . The most
common factors that could trigger the condition were tobacco smoking
. We have studied six large Indian families with premature-graying
of hair . The phenotype in these families is constituent with autosomal
dominant mode of inheritance . The pedigrees consist of 290 individuals
including 57 affecteds (25 males 32 females . The age of onset
ranged from early childhood to teenage with a graying range from 20-
40% hair and it increased with the advancement of age . Skipping of a
generation was observed in three pedigrees . Cytogenetic analysis of
two affecteds in each family did not show any anomaly . Systematic genome-wide
association or high density linkage studies with microchips
could be initiated in these families to identify the genetic loci . Email:
u_c_rao@hotmail .com
P06.038
A strong association of axillary osmidrosis with genotype of the
ABCC11 gene defining the earwax type
M. Tsuda 1,2 , N. Miwa 1,2 , M. Nakashima 1,3,2 , M. Nakano 4 , M. Nakashima 5 , K.
Yoshiura 1,2 , T. Ohta 6,2 , N. Niikawa 6,2 ;
1 Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki
University, Graduate School of Biomedical Sciences, Nagasaki, Japan, 2 Solution
Oriented Research of Science and Technology, Japan Science and
Technology Agency, Tokyo, Japan, 3 Department of Reconstruction and Plastic
Surger, Atomic Bomb Disease Institute, Nagasaki University Graduate School
of Biomedical Sciences, Nagasaki, Japan, 4 Department of Reconstruction and
Plastic Surgery, Atomic Bomb Disease Institute, Nagasaki University Graduate
School of Biomedical Sciences, Nagasaki, Japan, 5 Tissue and Histopathology
Section, Atomic Bomb Disease Institute, Nagasaki University Graduate School
of Biomedical Sciences, Nagasaki, Japan, 6 Research Institute of Personalized
Health Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan.
Two types of cerumen are known in humans: the wet type with brownish
sticky earwax, and the dry type lacking or reducing ceruminous
secretion . The wet type is predominant in populations of European
and African origin, while the dry type is often seen in Eastern Asian
populations . An association of axillary odor with the wet earwax type
among the Japanese was reported about 70 years ago . However,
the data of the two traits were based on phenotypical analysis by researchers
or on self-declaration by the subjects examined, because of
lacking of definite diagnostic methods. We recently found that a SNP
(rs17822931) of the ABCC11 gene is the determinant of the earwax
types . In the present study, a total of 79 individuals with axillary osmidrosis
(AO), who received a surgical operation to remove bilateral
axillary apocrine glands, were examined for their earwax types by genotyping
at the rs17822931 polymorphic locus . The earwax-type frequency
among them was compared with that in the general Japanese
population . The result showed a strong association between AO and
the wet earwax type (c2 = 90 .00, p < 2 .5x10-21) . In addition, immunohistochemical
study of the axillary and ceruminous apocrine gland
tissues using an anti-ABCC11-protein antibody revealed that ABCC11
is strongly expressed and localized in the apical membrane of the both
gland cells . The result indicates that ABCC11 protein (MRP8) functions
in the axillary apocrine gland as well as in the ceruminous gland, and
supports the association between axillary odor and earwax type .
P06.039
BcLi glucocrticoid receptor gene polymorhism and bone
mineralisation and methabolism in juvenile idiopathic arthritis
M. M. Kostik1 , A. A. Kozyreva2 , D. N. Baranov1 , N. N. Slizovskaya1 , V. I. Larionova1
;
1State Pediatric Medical Academy, Saint-Petersburg, Russian Federation,
2Federal heart, blood and endocrinology center, named by V.A. Almazov, Saint-
Petersburg, Russian Federation.
Juvenile idiopathic arthritis (JIA) is group of chronic inflammatory joint
disease with different complications, such as osteopenia . Some patients
receive only nonsteroid anti-inflammatory drugs (NSAID) and
other patients receive glucocorticoides .
The aim of our study was whether BclI glucocorticoid receptor (GCR)
gene polymorphism associated with bone mineralization and metabolism
disturbances in JIA children .
Objectives: we included in our study 122 JA children, 43 boys (35,2%)
and 79 girls (64,8%) . Glucocorticoides were administered 30 children
(24,6%), 3 boys and 27 girls . Another 92 JIA children were treated with
NSAID .
Methods: BclI GCR polymorphism was detected by polymerase chain
reaction with restriction assay [Fleury I . et all, 2003] . Osteopenia was
detected by dual-energy X-ray absorptiometry L1-L4 (Hologic QDR
4500C), with national pediatric referent database (Scheplyagina L .A .,
2005 et all) . Bone metabolic markers, such as total Ca, Ca ++ , phosphate,
and total alkaline phosphatise, osteocalcine, β-CrossLabs and
parathyroid hormone also were detected in our patients .
Results: We haven’t differences between genotypes and alleles distribution
between children, who received NSAID and glucocorticoides.
Girls with osteopenia (Zscore