2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
P06.286
Novel assay for tLR4 single nucleotide polymorphisms testing
in patients with acute coronary syndrome
S. A. Wisniewski, M. Popiel, A. Olasinska-Wisniewska, K. Kordel, S. Grajek,
R. Wachowiak;
University of Medical Sciences, Poznan, Poland.
Our aim was to investigate occurrence of: A896G(Asp299Gly),
C1196T(Thr399Ile) and other single nucleotide polymorphisms (SNP)
of toll-like receptor TLR4 in patients with ACS and healthy controls .
TLR4 is activated in the innate immunity response to lipopolysaccharide
LPS . TLR4-dependent reaction is involved in the pathogenesis of
atherosclerosis i .e . acute coronary syndrome (ACS) . SNP A896G and
SNP C1196T of TLR4 are postulated to occur more often in patients
with ACS .
Blood samples were collected from 50 patients with ACS within 24
hours from admission to ICCU and from 100 healthy controls . Genomic
DNA was extracted and TLR4 genetic variations A896G and C1196T
have been analyzed by genotyping with LightTyper system . Unknown
SNP’s of TLR4 were investigated with MSSCP .
Frequency of A896G(Asp299Gly) and C1196T(Thr399Ile) allele were in
ACS patients and controls: G - 0,03 and 0,01, resp ., A - 0,97 and 0,99,
resp .; C - 0,955 and 0,95, resp . and T - 0,045 and 0,05, resp . Very rare
homozygous G/G variant of A896G was found in one patient with ACS .
New cost-effective genotyping technique has been developed - allele
specific PCR reaction was performed with primer length modification
with poli(T), which allows analysis of multiplex PCR reaction .
Frequency of A896G and C1196T allele did not differ significantly
among patients with ACS and controls . However, relatively small number
of patients requires caution in extrapolating results to population
study. The second part of our study will be quantified assessment of
TLR4 expression: in controls, in patients during ACS and then in stable
period of CAD .
P06.287
Relation of TPH gene polymorphic variants to personality traits
associated with psychiatric disorders
A. Kazantseva 1 , D. Gaysina 1,2 , E. Khusnutdinova 1 ;
1 Institute of Biochemistry and Genetics, Ufa Scientific Centre of Russian Academy
of Sciencies, Ufa, Russian Federation, 2 MRC SGDP Centre, Institute of
Psychiatry, King’s College, London, United Kingdom.
Individual differences in personality are influenced by both environmental
and genetic factors . Enormous studies indicated association
between TPH1 A218C polymorphism and personality disorders (characterized
by impulsivity, anxiety and low extraversion) . It is likely that
genetically mediated variability of the TPH1 gene functioning can contribute
to individual differences in personality traits .
We aimed to define genotype effect of TPH1 A218C polymorphism
and to check possible TPH1*gender and TPH1*ethnicity interaction
effect on personality traits (assessed with the EPI and TCI questionnaires)
. We recruited 602 healthy individuals (men-206, women-396)
of Caucasian origin (Russians-214, Tatars-388) from Russia (mean
age±SD, 19 .85±2 .43 years) .
Association between C-allele and higher Extraversion
(p=0 .001;F=11 .127), and lower Harm Avoidance (p=0 .027;F=4 .922)
was observed, that was also reported in women and Tatars . Gender
and ethnicity specific differences on personality were detected, with
women and Tatars scoring higher on Harm Avoidance, Tatars scoring
lower on Extraversion . MANOVA (carried out with gender and
ethnicity as second factors) revealed the influence of TPH1*ethnicity
interaction on Extraversion (p=0 .032;F=4 .634) observed due to the
differences in this trait between Tatars with C-allele and A/A-genotype
(p=0 .000;F=15 .779); Tatars with A/A-genotype and Russians
with C-allele (p=0 .000;F=19 .770); Tatars and Russians with A/Agenotype
(p=0 .007;F=7 .820) . The same pattern of TPH1*ethnicity
interaction influence on Extraversion was demonstrated in women
(p=0 .043;F=4 .139) .
Current findings suggest that the variance in Extraversion and Harm
Avoidance could be explained by TPH1*ethnicity interaction, although
the single TPH1 genotype and ethnicity effect occurs .
This work was supported by RSCI grant 06-06-00163à and «Russian
Science Support Foundation» (to A .Kazantseva, D .Gaysina) .
P06.288
tUB gene polymorphisms are associated with anthropometry
and eating behavior in middle-aged women
J. V. van Vliet-Ostaptchouk 1 , C. Onland-Moret 2 , R. Shiri-Sverdlov 3 , P. van
Gorp 3 , P. Peeters 2 , C. Wijmenga 1,2 , M. Hofker 1,3 , Y. van der Schouw 2 ;
1 University Medical Center Groningen, Groningen, The Netherlands, 2 University
Medical Center Utrecht, Utrecht, The Netherlands, 3 Maastricht University,
Maastricht, The Netherlands.
The TUB gene, encoding an evolutionary conserved protein, is highly
expressed in the hypothalamus and might act as a transcription factor
. Mutations in TUB cause late-onset obesity, insulin-resistance and
neurosensory deficits in mice. An association of common variants in
the TUB gene with body weight in humans has been reported . The aim
was to investigate the relationship of single nucleotide polymorphisms
(SNPs) of the TUB gene (rs2272382, rs2272383 and rs1528133) with
both anthropometry and macronutrient intake in general population .
The association of SNPs in TUB with body composition and macronutrient
intake from a validated food frequency questionnaire was studied
in a population-based study of 1680 middle-aged Dutch women .
The minor allele C of the rs1528133 was significantly associated with
increased weight (+1 .88 kg, P = 0 .022) and BMI (+0 .56 units, P =
0 .05) . Both AG and AA genotypes for the rs2272382 were associated
with an increased energy intake from carbohydrates (0 .69%, P = 0 .04
and 1 .68%, P = 0 .003, respectively), mainly because of a higher intake
of mono- and disaccharides . Both these SNPs were also associated
with a higher glycemic load (GL) in the diet . The GL was higher among
those with AG and AA genotypes for the variant rs2272382 than
among the wild types (+1 .49 and +3 .89 units, respectively) . Carriers of
the minor allele C of rs1528133 were associated with an increased GL
of 1 .85 units compared with non-carriers .
Our results suggest that the effect of TUB on body composition might
be due to the increased intake of carbohydrates .
P06.289
Influence of several polymorphisms in the risk of antituberculosis
drug-induced hepatotoxicity in caucasian
population
D. Valverde 1 , V. Leiro 2 , A. Fernández-Villar 2 , L. Constenla 3 , R. Vázquez 2 , L.
Anibarro 4 , L. Piñeiro 2 ;
1 University of Vigo. Spain, Vigo, Spain, 2 Pulmonary Department, Hospital
Xeral-Cíes, Complexo Hospitalario de Vigo (CHUVI), Vigo, Spain, 3 Unidad de
Apoyo a la Investigación Biomédica, Complexo Hospitalario Universitario de
Vigo (CHUVI)., Vigo, Spain, 4 Internal Medicine Department, Hospital Provincial,
Complexo Hospitalario de Pontevedra (CHOP), Vigo, Spain.
Homozygous delection GSTM1 (glutathione S-transferase M1) polymorphism,
slow NAT2 (N-acetyltransferase 2) acetilator genotypes
and c1/c1 CYP2E1 genotype increase the risk of antituberculosis
drug-induced hepatotoxicity in Asian population . There are no studies
about these polymorphisms and the risk of antituberculosis drug-induced
hepatotoxicity in Caucasians .
Case-control prospective study of tuberculosis patients treated with
isoniazid, pyrazinamid and rifampin . Cases were patients with antituberculosis
drug-induced hepatotoxicity and controls patients without
this complication . After DNA extraction from periferic blood, GSTM1
and T1 null polymorphisms were performed by PCR and NAT2 slow
polymorphisms and CYP2E1 c1 and c2 polymorphisms by PCR and
RFLP .
We included 38 cases and 60 controls without differences in age, sex,
BMI and basal transaminases values . The homozygous delection at
GSTM1 locus was present in 34 .3% cases and 41 .7% controls (P =
0 .47) and at the GSTT1 locus in 48 .6% cases and 26 .7% controls (P
= 0 .03) . Slow NAT2 acetilator genotypes were present in 65 .8% cases
and 61% controls (P = 0 .67) . The 6*/7* genotype was only present in
cases (P = 0 .02) . CYP2E1 c1/c1 genotype was present in 86 .8% cases
and 87 .3% controls and c1/c2 genotype in 13 .2% cases and 12 .7%
controls (P = 0 .95) . The CYP2E1 c2/c2 was not found in any patient .
We did not find any relation between NAT2 slow genotypes and
CYPE1 c1/c1 genotype and the risk of antituberculosis drug-induced
hepatotoxicity .
Partial finance support by SOGAPAR (beca Almirall), Xunta de Galicia
(axuda PIGDIT05SAN21PR), FIS (PI052461) and SEPAR (beca
becario) .