Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish population.
OBJECTIVE
Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden.


METHODS
A total of 56 families with 117 affected individuals were included in the linkage study. Genotyping was performed with polymorphic microsatellite markers with an average distance of 4.5 cM on chromosome 5. In the association study, 275 cases of first-ever stroke were included together with 550 matched community controls. Polymorphisms were tested individually for association of PDE4D to stroke.


RESULTS
Maximum allele-sharing lod score in favor of linkage was observed at marker locus D5S424 (lod score=2.06; P=0.0010). Conditional logistic regression calculations revealed no significant association of ischemic stroke to the defined at-risk allele in PDE4D (odds ratio, 1.1; 95% confidence interval, 0.84 to 1.45). A protective effect may though be implied for 2 of the polymorphisms analyzed in PDE4D.


CONCLUSIONS
Using a candidate region approach in a set of stroke families from northern Sweden, we have replicated linkage of stroke susceptibility to the PDE4D gene region on chromosome 5q. Association studies in an independent nested case-control sample from the same geographically located population suggested that different alleles confer susceptibility/protection to stroke in the Icelandic and the northern Swedish populations.
Nilsson-Ardnor
Sofie
S
Department of Medical Biosciences, Umeå University, SE-901 87, Umeå, Sweden.
Wiklund
Per-Gunnar
PG
Lindgren
Petter
P
Nilsson
Anna Karin
AK
Janunger
Tomas
T
Escher
Stefan A
SA
Hallbeck
Björn
B
Stegmayr
Birgitta
B
Asplund
Kjell
K
Holmberg
Dan
D
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000465:Algorithms; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D048909:Diabetes Complications / Q000235:genetics; D005091:Exons; D005192:Family Health; D005787:Gene Frequency / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007055:Iceland; D007511:Ischemia; D015810:Linkage Disequilibrium; D008126:Lod Score; D018895:Microsatellite Repeats; D015233:Models, Statistical; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000235:genetics; D013548:Sweden
D005819:Genetic Markers; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human