An extended association screen in multiple sclerosis using 202 microsatellite markers targeting apoptosis-related genes does not reveal new predisposing factors.
Apoptosis, the programmed death of cells, plays a distinct role in the etiopathogenesis of Multiple sclerosis (MS), a common disease of the central nervous system with complex genetic background. Yet, it is not clear whether the impact of apoptosis is due to altered apoptotic behaviour caused by variations of apoptosis-related genes. Instead, apoptosis in MS may also represent a secondary response to cellular stress during acute inflammation in the central nervous system. Here, we screened 202 apoptosis-related genes for association by genotyping 202 microsatellite markers in initially 160 MS patients and 160 controls, both divided in 4 sets of pooled DNA samples, respectively. When applying Bonferroni correction, no significant differences in allele frequencies were detected between MS patients and controls. Nevertheless, we chose 7 markers for retyping in individual DNA samples, thereby eliminating 6 markers from the list of candidates. The remaining candidate, the ERBB3 gene microsatellite, was genotyped in additional 245 MS patients and controls. No association of the ERBB3 marker with the disease was detected in these additional cohorts. In consequence, we did not find further evidence for apoptosis-related genes as predisposition factors in MS.
Gödde
René
R
Department of Human Genetics, Ruhr-University, Bochum, Germany. rene.goedde@ruhr-uni-bochum.de
Brune
Stefanie
S
Jagiello
Peter
P
Sindern
Eckhart
E
Haupts
Michael
M
Schimrigk
Sebastian
S
Müller
Norbert
N
Epplen
Jörg T
JT
D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D005819:Genetic Markers