2009 Vienna - European Society of Human Genetics

Evolutionary and population genetics, and Genetic epidemiology
Austria, 2 First Department of Internal Medicine, Paracelsus Private Medical
University, Salzburg, Austria, 3 Cardiovascular Genetics Division, University of
Utah School of Medicine, Salt Lake City, UT, United States.
Background: Several recent studies highlight that especially rare mutations
exhibit a strong influence on many atherosclerosis-related phenotypes.
Since the ATGL lipase catalyzes the rate-limiting step of the
lipolysis, it represents an important candidate gene for the investigation
of the influence of rare mutations on the lipid metabolism.
Aim of the study: To capture the entire genetic variation of ATGL in a
large healthy working population with a special focus on potentially
regulatory non-coding regions.
Methods: The full ATGL gene region including the predicted promoter
was screened for mutations in 1473 individuals of the SAPHIR study
by using a pooled Ecotilling approach. All polymorphisms were confirmed
by sequencing, bioinformatically characterized and four common
SNPs (2 of them being previously unknown) were finally genotyped
in SAPHIR and in the Utah obesity case-control study.
Results: We detected 58 new, previously unknown mutations: 33 private
mutations, 20 SNPs with a frequency below 5% and 5 common
polymorphisms. Eleven mutations affected the protein sequence and
~30% of all detected variants were located in the 5’ upstream region.
Interestingly, only 16 of the 25 reported dbSNPs could be confirmed.
Association studies with phenotypes from lipoprotein metabolism are
currently ongoing.
Conclusion: Rare mutations are relatively common and may represent
an important factor for the diversity of lipid-related phenotypes in a
population. We found several new mutations to be located in potentially
functional sites such as exons and promoters. This highlights the
current lack, respectively need, of comprehensive information about
the distribution and impact of rare genetic variants.
P10.06
APOA5 gene polymorphism and triglyceride levels in metabolic
syndrome patients
P. Kisfali 1 , M. Mohas 2 , A. Maasz 1 , F. Hadarits 3 , T. Oroszlan 4 , Z. Bujtor 4 , Z. Bagosi
4 , B. Gasztonyi 4 , I. Wittmann 2 , B. Melegh 1 ;
1 Department of Medical Genetics and Child Development, University of Pécs,
Pécs, Hungary, 2 2nd Department of Medicine and Nephrological Center, University
of Pécs, Pécs, Hungary, 3 Central Laboratory, Markusovszky County
Hospital, Szombathely, Hungary, 4 2nd Department of Medicine, Zala County
Hospital, Zalaegerszeg, Hungary.
Metabolic syndrome (MS) is a clustering of abdominal obesity, increased
triglycerides, low levels of high density lipoprotein cholesterol,
high blood pressure, and elevated fasting glucose levels and consists
of multiple risk factors that are increasing the cardiovascular mortality.
Naturally occurring variants of the apolipoprotein A5 gene have been
associated with increased triglyceride level and have been found to
confer risk for cardiovascular diseases. In our study four haplotype-tagging
polymorphisms, the T-1131C, IVS3+G476A, T1259C, and C56G
alleles were analyzed. A total of 325 metabolic syndrome patients were
genotyped by polymerase chain reaction - restriction fragment length
polymorphism. MS patients were separated into four quartile (q) groups
based on triglyceride levels (q1: TG2.83 mmol/l). We observed significant
relationships between three APOA5 minor allele carrier frequencies
and plasma triglyceride quartiles: -1131C (q1: 4.94%; q2: 8.64%; q3:
11.6%; q4: 12.3%), IVS3+476A (q1: 4.32%; q2: 7.4%; q3: 10.36%; q4:
11.1%), 1259C (q1: 4.94%; q2: 7.41%; q3: 10.4%; q4: 11.7%). The serum
total cholesterol levels did not show allele-dependent differences.
The findings presented here revealed unique arrangement of APOA5
minor alleles in MS.
P10.07
Determination of genetic profiles associated with atopic asthma
in madeira population
A. G. Berenguer1 , R. Câmara2 , A. T. Fernandes1 , S. Oliveira2 , A. Brehm1 ;
1 2 Human Genetics Laboratory, Funchal, Portugal, Imunoallergology Unit, Central
Hospital of Funchal, Funchal, Portugal.
Atopic asthma arises from gene-environment interactions. There are
many genes associated to asthma and their combination may enlighten
some results obtained in other studies regarding different populations.
A sample of 100 children with atopic asthma was compared with 105
individuals from Madeira Island population. Five different polymorphisms
with proven association to the asthmatic disease development
were studied, namely IL4-590 C/T (rs2243250), ADAM33 S1 G/A
(rs3918396), GSDML C/T (rs7216389), STAT-6 C/T (rs324011) and
IL13 +2044 G/A (rs20541). Genotyping was performed by Real Time
PCR. Allelic and genotypic frequencies were determined for each polymorphism.
We also determined the genetic profile of each individual by
combining the five polymorphisms. Comparisons between both populations
were done using χ 2 test for each polymorphism and the Fisher’s
test to compare all genetic profiles. Significant differences have been
found amongst studied populations for IL4-590 (C/T) (p