TY  - JOUR
A1  - Schrewe, L.
A1  - Lill, C. M.
A1  - Liu, T.
A1  - Salmen, A.
A1  - Gerdes, L. A.
A1  - Guillot-Noel, L.
A1  - Akkad, D. A.
A1  - Blaschke, P.
A1  - Graetz, C.
A1  - Hoffjan, S.
A1  - Kroner, A.
A1  - Demir, S.
A1  - Böhme, A.
A1  - Rieckmann, P.
A1  - El Ali, A.
A1  - Hagemann, N.
A1  - Hermann, D. M.
A1  - Cournu-Rebeix, I.
A1  - Zipp, F.
A1  - Kümpfel, T.
A1  - Buttmann, M.
A1  - Zettl, U. K.
A1  - Fontaine, B.
A1  - Bertram, L.
A1  - Gold, R.
A1  - Chan, A.
T1  - Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS
JF  - Journal of Neuroinflammation
N2  - Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. 
Methods: MOG\(_{35-55}\) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. 
Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE\(^{-/-}\)) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE\(^{-/-}\) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naive animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. 
Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.
KW  - immune
KW  - apoE
KW  - gender
KW  - inflammation
KW  - association studies in genetics
KW  - apoe
KW  - CNS disease
KW  - system
KW  - multiple sclerosis
KW  - MSSS
KW  - experimental autoimmune encephalomyelitis
KW  - disease severity
KW  - cognitive function
KW  - Alzheimer disease
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136252
VL  - 12
IS  - 234
ER  - 
TY  - JOUR
A1  - Munz, Matthias
A1  - Richter, Gesa M.
A1  - Loos, Bruno G.
A1  - Jepsen, Søren
A1  - Divaris, Kimon
A1  - Offenbacher, Steven
A1  - Teumer, Alexander
A1  - Holtfreter, Birte
A1  - Kocher, Thomas
A1  - Bruckmann, Corinna
A1  - Jockel-Schneider, Yvonne
A1  - Graetz, Christian
A1  - Munoz, Loreto
A1  - Bhandari, Anita
A1  - Tennstedt, Stephanie
A1  - Staufenbiel, Ingmar
A1  - van der Velde, Nathalie
A1  - Uitterlinden, André G.
A1  - de Groot, Lisette C. P. G. M.
A1  - Wellmann, Jürgen
A1  - Berger, Klaus
A1  - Krone, Bastian
A1  - Hoffmann, Per
A1  - Laudes, Matthias
A1  - Lieb, Wolfgang
A1  - Andre, Franke
A1  - Dommisch, Henrik
A1  - Erdmann, Jeanette
A1  - Schaefer, Arne S.
T1  - Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus
JF  - Scientific Reports
N2  - Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (PAgP-Ger < 0.05; PCAD < 5 × 10−8; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02–1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05–1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.
KW  - vesicle-associated membrane protein 8 (VAMP8)
KW  - ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS7)
KW  - shared genetic basis
KW  - genome-wide association studies (GWAS)
KW  - GWAS meta-analysis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231647
VL  - 8
ER  -