TY  - THES
A1  - Juling, Martin Johannes
T1  - Untersuchung der HBV-Genotypen bei antiviral behandelten Hepatitis B-Patienten im Zeitraum von 1997 bis 2004 an der Universitätsklinik Würzburg
T1  - Distribution of HBV genotypes among chronic hepatitis B infected patients from universityhospital Wuerzburg in 1997 till 2004
N2  - Von den acht bekannten HBV-Genotypen sind die Genotypen A und D in Europa vorherrschend, Genotyp A in Nordwesteuropa, Genotyp D im Mittelmeerraum und in Südosteuropa. Dies bestätigte sich auch in der vorliegenden Studie, bei der von 62 genotypisierten Proben 91,9 % diesen beiden Genotypen zugeordnet werden konnten. Genotyp D war mit 64,5 % (40 Patienten) vorherrschend. Es folgten der Genotyp A (17 Patienten) und der Genotyp C (4 Patienten). In einem Fall wurde Genotyp B nachgewiesen. Deutschland als Herkunftsland war bei Patienten mit Genotyp A signifikant häufiger vertreten als bei Patienten mit Genotyp D. Der relativ hohe Genotyp D-Anteil ist möglicherweise darauf zurückzuführen, dass durch zunehmende Immigration das Auftreten verschiedener Genotypen beispielsweise aus dem südosteuropäischen Raum begünstigt wird. Patienten mit Genotyp A sprechen häufig besser auf IFN-alpha an, so dass eine Therapie mit Nukleosid- bzw. Nukleotidanaloga nicht erforderlich ist. Diese Patienten wurden somit à priori nicht in dieser Studie erfasst, was eine mögliche Erklärung dafür ist, dass der Genotyp A-Anteil mit 27,4 % relativ gering ausfiel. Bei der Untersuchung von statistischen Zusammenhängen zwischen HBV-Genotyp und Patientenalter, Geschlecht, Viruslast und Therapiedauer ergaben sich keine signifikanten Ergebnisse. Diese Studie bietet Basisinformationen zur Genotypverteilung in Deutschland. Bezüglich einer Korrelation zwischen den verschiedenen HBV-Genotypen und demographischen, virologischen sowie klinischen Charakteristika wird es künftig weiterer Studien bedürfen.
N2  - Among the eight known HBV-genotypes, genotype A and D dominate in Europe. This study established the prevalence of different HBV genotypes in 62 patients from universityhospital Wuerzburg, Germany. The prevalences of genotypes A and D were 27,4% and 64,5%, for genotypes B and C 1,6% and 6,5%. The results indicated that genotypes A and D are the predominat genotypes in German patients with chronic HBV infection.
KW  - Hepatitis B
KW  - Genotyp
KW  - Lamivudin
KW  - Interferon <alpha->
KW  - Nucleosidanaloga
KW  - Nucleotidanaloga
KW  - Genotypverteilung
KW  - Hepatitis B
KW  - genotype
KW  - distribution
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-48789
ER  - 
TY  - JOUR
A1  - Togninalli, Matteo
A1  - Seren, Ümit
A1  - Meng, Dazhe
A1  - Fitz, Joffrey
A1  - Nordborg, Magnus
A1  - Weigel, Detlef
A1  - Borgwardt, Karsten
A1  - Korte, Arthur
A1  - Grimm, Dominik G.
T1  - The AraGWAS Catalog: a curated and standardized Arabidopsis thaliana GWAS catalog
JF  - Nucleic Acids Research
N2  - The abundance of high-quality genotype and phenotype data for the model organism Arabidopsis thaliana enables scientists to study the genetic architecture of many complex traits at an unprecedented level of detail using genome-wide association studies (GWAS). GWAS have been a great success in A. thaliana and many SNP-trait associations have been published. With the AraGWAS Catalog (https://aragwas.1001genomes.org) we provide a publicly available, manually curated and standardized GWAS catalog for all publicly available phenotypes from the central A. thaliana phenotype repository, AraPheno. All GWAS have been recomputed on the latest imputed genotype release of the 1001 Genomes Consortium using a standardized GWAS pipeline to ensure comparability between results. The catalog includes currently 167 phenotypes and more than 222 000 SNP-trait associations with P < 10\(^{-4}\), of which 3887 are significantly associated using permutation-based thresholds. The AraGWAS Catalog can be accessed via a modern web-interface and provides various features to easily access, download and visualize the results and summary statistics across GWAS.
KW  - model organism
KW  - genotype
KW  - phenotype
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158727
VL  - 46
IS  - D1
ER  - 
TY  - JOUR
A1  - Stein, Kiera
A1  - Maruf, Abdullah Al
A1  - Müller, Daniel J.
A1  - Bishop, Jeffrey R.
A1  - Bousman, Chad A.
T1  - Serotonin transporter genetic variation and antidepressant response and tolerability: a systematic review and meta-analysis
JF  - Journal of Personalized Medicine
N2  - Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.
KW  - 5-HTTLPR
KW  - genotype
KW  - pharmacogenetics
KW  - antidepressant
KW  - efficacy
KW  - tolerability
KW  - SLC6A4
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252294
SN  - 2075-4426
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Seren, Ümit
A1  - Grimm, Dominik
A1  - Fitz, Joffrey
A1  - Weigel, Detlef
A1  - Nordborg, Magnus
A1  - Borgwardt, Karsten
A1  - Korte, Arthur
T1  - AraPheno: a public database for Arabidopsis thaliana phenotypes
JF  - Nucleic Acids Research
N2  - Natural genetic variation makes it possible to discover evolutionary changes that have been maintained in a population because they are advantageous. To understand genotype–phenotype relationships and to investigate trait architecture, the existence of both high-resolution genotypic and phenotypic data is necessary. Arabidopsis thaliana is a prime model for these purposes. This herb naturally occurs across much of the Eurasian continent and North America. Thus, it is exposed to a wide range of environmental factors and has been subject to natural selection under distinct conditions. Full genome sequencing data for more than 1000 different natural inbred lines are available, and this has encouraged the distributed generation of many types of phenotypic data. To leverage these data for meta analyses, AraPheno (https://arapheno.1001genomes.org) provide a central repository of population-scale phenotypes for A. thaliana inbred lines. AraPheno includes various features to easily access, download and visualize the phenotypic data. This will facilitate a comparative analysis of the many different types of phenotypic data, which is the base to further enhance our understanding of the genotype–phenotype map.
KW  - phenotype
KW  - arabidopsis
KW  - genotype
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147909
VL  - 45
IS  - D1
ER  - 
TY  - JOUR
A1  - Lenders, Malte
A1  - Weidemann, Frank
A1  - Kurschat, Christine
A1  - Canaan-Kühl, Sima
A1  - Duning, Thomas
A1  - Stypmann, Jörg
A1  - Schmitz, Boris
A1  - Reiermann, Stefanie
A1  - Krämer, Johannes
A1  - Blaschke, Daniela
A1  - Wanner, Christoph
A1  - Brand, Stefan-Martin
A1  - Brand, Eva
T1  - Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant
JF  - Orphanet Journal of Rare Diseases
N2  - Background
Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma.

Methods
To determine the clinical impact of the alpha-Galactosidase A (GLA) p.A143T/ c.427G > A variation, we retrospectively analyzed 25 p.A143T patients in comparison to 58 FD patients with other missense mutations.

Results
p.A143T patients suffering from stroke/ transient ischemic attacks had slightly decreased residual GLA activities, and/or increased lyso-Gb3 levels, suspecting FD. However, most male p.A143T patients presented with significant residual GLA activity (~50 % of reference), which was associated with normal lyso-Gb3 levels. Additionally, p.A143T patients showed less severe FD-typical symptoms and absent FD-typical renal and cardiac involvement in comparison to FD patients with other missense mutations. Two tested female p.A143T patients with stroke/TIA did not show skewed X chromosome inactivation. No accumulation of neurologic events in family members of p.A143T patients with stroke/transient ischemic attacks was observed.

Conclusions
We conclude that GLA p.A143T seems to be most likely a neutral variant or a possible modifier instead of a disease-causing mutation. Therefore, we suggest that p.A143T patients with stroke/transient ischemic attacks of unknown etiology should be further evaluated, since the diagnosis of FD is not probable and subsequent ERT or chaperone treatment should not be an unreflected option.
KW  - Fabry disease
KW  - genotype
KW  - lyso-Gb3
KW  - variant of unknown significance
KW  - GLA mutation
KW  - late-onset
KW  - stroke
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166559
VL  - 11
IS  - 54
ER  -