Evaluation of genetic risk factors for silent brain infarction.
OBJECTIVE
Silent brain infarction (SBI) is often found with white matter hyperintensity. A recent genetic study on elderly twins indicated that the susceptibility to white matter hyperintensity was largely determined by genetic factors, implying the existence of genetic susceptibility for SBI as well. We therefore studied 3 genetic polymorphisms in SBI, the deletion/insertion polymorphism of angiotensin-converting enzyme (ACE) gene, the apolipoprotein(a) [apo(a)] size polymorphism, and the T677C polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene, by a case-control study.


METHODS
By MRI, 147 subjects with SBI and 214 without cerebral infarctions (control group) were selected from participants of a health examination of the brain. Seventy-four patients with symptomatic subcortical infarction (SSI) from the same area were also included in the study. In addition to the control group, 2 more reference populations were recruited. Typing of the apo(a) size polymorphism was done by Western blotting with the use of an anti-apo(a) antibody. Genotypes of ACE and MTHFR were determined by polymerase chain reaction amplification of the genomic DNA and subsequent restriction enzyme digestion.


RESULTS
The ACE polymorphism was not associated with either SBI or SSI. In contrast, the small apo(a) was associated with both SSI and SBI. The MTHFR polymorphism was associated only with SSI. The association of MTHFR and apo(a) was greater in the younger subjects.


CONCLUSIONS
Among the 3 genetic polymorphisms studied, only the apo(a) size polymorphism is a risk factor for SBI.
Notsu
Y
Y
Central Clinical Laboratory, Shimane Medical University, Izumo, Japan.
Nabika
T
T
Park
H Y
HY
Masuda
J
J
Kobayashi
S
S
D000368:Aged; D001054:Apolipoproteins A / Q000235:genetics; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics* / Q000503:physiopathology; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics
D001054:Apolipoproteins A; D004251:DNA Transposable Elements; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A