Evaluation of genetic risk factors for silent brain infarction

Background and Purpose-Silent brain infarction (SBI) is often found with wh ite matter hyperintensity. A recent genetic study on elderly twins indicate d that the susceptibility to white matter hyperintensity was largely determ ined by genetic factors, implying the existence of genetic susceptibility f or SBI as well. We therefore studied 3 genetic polymorphisms in SBI, the de letion/insertion polymorphism of angiotensin-converting enzyme (ACE) gene, the apolipoprotein(a) [apo(a)] size polymorphism, and the T677C polymorphis m of methylenetetrahydrofolate reductase (MTHFR) gene, by a case-control st udy. 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 (S SI) 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 a po(a) size polymorphism was done by Western blotting with the use of an ant i-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.