2009 Vienna - European Society of Human Genetics

Statistical genetics, includes Mapping, linkage and association methods
amines and the enzymes for their degradation. These endogenous
catecholamines synthesized by immune cells can regulate immune
functions, including cellular proliferation, differentiation, apoptosis and
cytokine production. In vitro, dopamine inhibits the proliferation of activated
T cells and their cytokine secretion.
Changes in the dopamine system are influenced not only by dopamine
itself, but also by dopamine receptors that are encoded by five different
dopamine receptor genes (DR1-DR5). .Metabolic abnormalities
of catecholamines in immune cells could be related to autoimmune
disease. Several observation indicate that catechoamines and their
receptors may play a part in the pathogenesis of chronic inflammatory
conditions, such as rheumatoid arthritis (RA). We have therefore
asked whether changes in the dopaminergic system are associated
with RA.
In the present study, we investigated dopamine receptor gene expression
in PBMCs of 40 RA patients and 40 healthy individuals by
RT-PCR. Quantitative gene expression analysis was made by realtime-PCR
using primer pairs specific for the five dopamine receptors
and beta-actin as internal control. We found that all types of dopamine
receptors are present in lymphocytes of normal individuals and RA patients.
However, a significant difference of DR2 and DR4 gene expression
profiles was seen in RA, as compared to healthy individuals. We
conclude that there is a quantitative significant difference of dopamine
gene receptor expression in RA.
P08.26
mutation analysis of the human fatty acid amide hydrolase gene
and the risk of drug addiction
R. Kodiappan 1 , R. Rosli 1 , L. Rampal 2 , S. M. Sidik 3 , L. K. Hwa 4 ;
1 Clinical Genetics Unit, Department of Obstetrics and Gynecology, Faculty of
Medicine and Health Sciences, University Putra Malaysia, Serdang, Selangor,
Malaysia, 2 Department of Community Health, Faculty of Medicine and Health
Sciences, University Putra Malaysia, Serdang, Selangor, Malaysia, 3 Department
of Pathology, Faculty of Medicine and Health Sciences, University Putra
Malaysia, Serdang, Selangor, Malaysia, 4 Division of Molecular Medicine, The
Walter and Eliza Hall Institute of Medical Research, University of Melbourne,
Australia.
Addiction to illicit drugs is a neurobehavioral disorder of complex origins.
Although social and psychological factors contribute to addiction,
genetic factors explicitly weigh in. To understand the role of genetic
variations in vulnerability to drug addiction, the nature of population
genetics has to be characterized by identifying the single nucleotide
polymorphisms (SNPs) in candidate genes and performing association
studies. Here, we investigated the SNPs in the coding regions of
the fatty acid amide hydrolase (FAAH) gene which encodes the principal
endocannabinoid-inactivating enzyme. A missense mutation in
this gene, c.385C>A, has been reported to contribute to the functional
alteration in the endocannabinoid system. Although a link between this
polymorphism and drug abuse among white ancestral subjects has
been reported, the specific allelic frequencies often vary in different
populations. Hence, to explore this hypothesis in Malaysian subjects,
we conducted a case-control study which included 80 drug addicts and
80 healthy controls. DNA sequencing analysis revealed a significant
(p0.05). A subanalysis of subjects depending their body mass
index (BMI) status revealed no significant impact of the 3 polymorphisms
and Q-delT-G haplotype on obesity. In conclusion our study
indicated the potential role of an intronic polymorphism IVS20delT-11
with type 2 diabetes and no evidence of SNPs and haplotype association
of ENPP1 gene with obesity in Japanese
P08.28
mEFV genotyping for diagnostics and treatment of FmF
T. F. Sarkisian, H.S. Hayrapetyan, G.R.Shahsuvaryan, A.R.Yeghiazaryan;
Center of Medical Genetics, Yerevan, Armenia.
FMF (Familial Mediterranean Fever) is characterized by recurrent,
short (2-4 days) episodes of fever, accompanied by severe pain in the
abdomen, chest or joints, and sometimes associated with erysipelaslike
erythema. The most severe complication is progressive renal amyloidosis
(RA). FMF is caused by a number of mutations in the MEFV
gene located on chromosome 16p, encoding pyrin protein, which normally
acts as a mediator in control of inflammation. Molecular genetic
analysis significantly improves early and correct diagnosis of FMF, and
allows to commence lifelong treatment of affected individuals with colchicine.
Frequency of the mutations of MEFV gene is extremely high in
Armenian population. We have reported about the molecular diagnostics
of more than 10000 FMF patients in Armenians.
In our FMF patients the colchicine largely prevents the development
of attacks and renal amyloidosis (RA). Adequate colchicinotherapy
delays RA progression in FMF/RA patients. In a few cases the effect
of colchicine remains controversial. We confirm, that genotyping is
assisting in prediction of the response to colchicine treatment. FMF
homozygous patients for M694V mutation present a more severe phenotype
and show a limited response to colchicine at a nephrotic stage
of RA. In contrast, FMF patients with other genotypes still have a good
chance to ameliorate of the nephrotic syndrome and to maintain renal
function.
Conclusion: According to our results, the genotyping is recommended
for all siblings of FMF patients and to search for other autoinflammatory
periodic fever syndromes among patients with specific clinical
symptoms but without MEFV mutations.
P08.29
GAA Repeat Polymorphism and Cytogenetic findings in Turkish
Friedreich’s Ataxia Patients
F. Koc 1 , M. Yilmaz 2 , A. Guzel 2 , S. Kocatürk Sel 2 , H. Kasap 2 ;
1 Cukurova University School of Medicine Department of Neurology, Adana,
Turkey, 2 Cukurova University School of Medicine Department of Medical Biology
and Genetics, Adana, Turkey.
Friedreich ataxia (FA), a progressive heredodegenerative disorder, is
one of the most common form of autosomal recessive ataxias. FA is
the result of a gene mutation at the centromeric region of chromosome
9 (9q13-21.1) which is the site of the gene encoding for the 210-aminoacid
protein frataxin.
Results of GAA repeat polymorphism in 61 family members of 30 typical
FRDA patients were reported. GAA triplet repeat size ranged from
aproximately 7 to 34 in normal alleles and from 66 to 1300 in mutant
alleles. Fourty six patients were homozygous for GAA expansion and
size of expanded alleles differed from 425 to 1300 repeats. Children
2 and 6 years old of one family had homozygous GAA expansions
reaching 925 repeats. All 30 families studied had at least 1 afflicted