2009 Vienna - European Society of Human Genetics

Statistical genetics, includes Mapping, linkage and association methods
binding cassette subfamily B member 1 (ABCB1) are associated with
wide inter-individual heterogeneity in oral bioavailability. We therefore,
investigated pharmacogenomic associations in CYP3A4, CYP3A5 and
ABCB1 genes with allograft outcome in a cohort of 297 renal transplant
recipients.
Methods: 224 patients on CsA and 73 patients on Tac based immunosuppression
regimen were genotyped for single nucleotide polymorphisms
(SNPs) in CYP3A5 (CYP3A5*2, CYP3A5*3 , CYP3A5*4), CY-
P3A4 (CYP3A4*1B, CYP3A4*6, CYP3A4*18) and ABCB1 (-129T>C,
1236C>T, 2064-76T>A, 2677G>T, 3435C>T) and correlated with CsA/
Tac dose requirement (mg/kg/day) and dose adjusted CsA (C 2 )/Tac
(T 0 ) blood levels (concentration/dose ratio) at 1month and 3months
post transplantation.
Results: Daily dose requirements were 10-22% and 20-40% higher
for CsA and Tac, respectively, in CYP3A5*3 *1/*1 genotype patients
as compared to *3/*3 patients at 1 and 3 months post transplantation.
Significant correlation of CYP3A5*3 with dose adjusted levels of
CsA (r 2 =0.047, p=0.001) and Tac (r 2 =0.278, pT GG genotype (CsA, C 2 p=0.032; Tac T 0 , p=0.001) suggesting
that for a given dose their CsA/Tac blood concentration was lower.
The GG genotype was further associated with lower allograft survival
as indicated by Kaplan-Meier analysis (p=0.007).
Conclusion: Identification of CYP3A5*3 *1/*1 and ABCB1 2677GG
patients with significantly lower dose-adjusted concentrations suggest
the requirement of higher CsA/Tac dose to reach therapeutic concentrations.
The study may supplement pre-transplant pharmacogenomic
information for individualizing immunsuppressant doses.
P08.57
Association study of HLA-DRB1 alleles with Rheumatoid
Arthritis in tunisian patients
M. Ben Hamad 1 , N. Mahfoudh 2 , S. Marzouk 3 , G. Chabchoub 1 , Z. Bahloul 3 , F.
Fakhfakh 1 , H. Ayadi 1 , H. Makni 2 , A. Maalej 1 ;
1 Laboratoire de Génétique Moléculaire Humaine,Faculté de Médecine, sfax,
Tunisia, 2 Service du Laboratoire, CHU Hedi Chaker, sfax, Tunisia, 3 Service de
Médecine Interne, CHU Hedi Chaker, sfax, Tunisia.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized
by progressive joint destruction and autoantibody formation.
Auto-antibodies elaborated include anti-citrullinated protein/peptide
antibodies (ACPA) and anti-rheumatoid factor (RF). Both genetic and
environmental factors, and their interaction, play a role in the development
of RA. A common set of alleles at the HLA-DRB1 locus (the
shared epitope alleles) has been associated with RA in populations
with white European and Asian ancestry. The aim of this study is to
investigate the involvement of HLA-DRB1 alleles in the susceptibility
to RA in the Tunisian population. A set of 143 RA patients and 123 Tunisian
controls was analyzed for HLA-DRB1 alleles using polymerase
chain reaction/sequence specific primers (PCR/SSP). Association was
assessed based on the χ 2 test and odds ratios (ORs) with 95% confidence
intervals (CIs). Our results showed a higher frequency but non
significant association of HLA-DRB1*04 and HLA-DRB1*10 alleles
in patients compared to the controls (23.43% versus 16.26%, 6.64%
versus 2.44%; respectively). However, the stratification of our patients
according to immunological and clinical data showed a significant difference
of HLA-DRB1*04 allele in the subgroup of patients with ACPA
(p c = 0.023; OR= 2.08; CI= [1.31-3.3]) and the subgroup of patients
with RF (p c = 0.023; OR= 2.09; CI= [1.31-3.34]). Moreover, the subdivision
of patients according to sex, extra-articular involvement and
radiographic damage showed no significant difference (p>0.05). Our
results indicated that the HLA-DRB1*04 allele was significantly associated
with RA susceptibility in both subgroups with ACPA and RF.
P08.58
Comparative analysis of the first trimeser serum markers’ levels
in twin and singleton pregnancies
D. T. Tursunova, N. A. Karetnikova, E. A. Goncharova, V. A. Bakharev;
Research Center for obstetrics, gynecology and perinatology, Moscow, Russian
Federation.
Objectives: to look at the differences in the serum markers’ level between
singleton and multiple pregnancies.
Methods: in total 22 women in the age of 24 to 41 years old with twin
pregnancy were recruited in the study group. Control group consisted
of 22 women with spontaneous singleton pregnancy. Serum markers
(PAPP-A and free β-HCG) and fetal nuchal translucency (NT) thickness
were measured at 10+0 to 13+0 weeks of pregnancy. All the
women with twins underwent chorionbiopsy due to increased NT thickness
or increased maternal age.
Results: Differences in the median of PAPP-A were significantly lower
in singletons (1.09; 0.27 - 2.48) vs multiple pregnancies (2.69; 0.76
- 6.19), p