Genotype and haplotype association study of the STRK1 region on 5q12 among Japanese: a case-control study.
OBJECTIVE
Cerebral infarction is thought to be a multifactorial disease that is affected by several environmental factors and genetic variants. Gretarsdottir et al identified a candidate locus (STRK1) for cerebral infarction with a significant logarithm of odds score at 5q12 in whites in 2002 and subsequently identified the PDE4D gene as a susceptibility gene at this locus in 2003. The aims of this haplotype-based case-control study were to confirm, using microsatellite markers and single-nucleotide polymorphisms (SNPs), whether PDE4D is also a susceptibility gene for cerebral infarction in Japanese subjects.


METHODS
Cerebral infarction was defined as noncardiogenic ischemic stroke with signs and symptoms lasting >1 month in duration. We genotyped 208 Japanese cerebral infarction patients and 270 non-cerebral infarction controls for 31 SNPs, 3 dinucleotide microsatellites, and 1 tetranucleotide variable number of tandem repeat. Haplotypes were constructed and their frequencies compared between the cerebral infarction patients and the controls.


RESULTS
The haplotype-based case-control study revealed that in addition to the region of the PDE4D gene (P=0.002), another region (P<0.001) also existed within the STRK1 locus.


CONCLUSIONS
The region of the PDE4D gene and the other newly detected region within the STRK1 locus were associated with cerebral infarction.
Nakayama
Tomohiro
T
Division of Receptor Biology, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan. tnakayam@med.nihon-u.ac.jp
Asai
Satoshi
S
Sato
Naoyuki
N
Soma
Masayoshi
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics; D002895:Chromosomes, Human, Pair 5; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human