title: Genetic predisposition to neurological symptoms in lacunar infarction.
abstract: OBJECTIVE
  Lacunar infarction is a unique stroke entity with characteristic symptoms. However, it is often silent clinically. The possible genetic predisposition to symptoms of lacunar infarction was investigated.
  
  
  METHODS
  One-hundred and fifty-one patients with lacunar stroke were consecutively recruited. Lacunar stroke was diagnosed based on both neurological symptoms and lacunar lesion(s), demonstrated by MRI, that were responsible for the symptoms. One-hundred and fifty control subjects with MRI-proven lacunar lesions without neurological symptoms served as controls. There was no significant difference in age, sex and prevalence of known risk factors between cases and controls. Insertion and deletion polymorphisms of the angiotensin-converting enzyme gene (ACE), M235T substitution of the angiotensinogen gene (AGT), and A1133C substitution of type 1 receptor of the angiotensin II gene were determined.
  
  
  RESULTS
  The frequency of ACE D allele was significantly higher in symptomatic patients compared with asymptomatic subjects (0.44 vs. 0.36, p < 0.05). The genotype distribution of AGT was significantly different between symptomatic and asymptomatic patients (chi(2) = 6.6, p = 0.037). Multiple logistic regression analysis revealed that ACE gene and AGT genotypes were independently associated with the neurological manifestation of lacunar infarction. In subjects with 1 lacuna, the odds ratio of the ACE DD genotype for symptomatic manifestation was 4.98 (95% CI 1.25-19.9). In subjects with 4 or more lacunae, the odds ratio of the ACE II genotype for symptomatic manifestation was 0.24 (95% CI 0.10-0.56). Furthermore, the ACE gene polymorphism was significantly different between symptomatic patients with a single lacuna and asymptomatic subjects with 4 or more multiple lacunar infarctions (chi(2) = 10.6, p = 0.005).
  
  
  CONCLUSIONS
  These findings suggest that 2 subtypes of lacunar infarction, single symptomatic lacuna and multiple asymptomatic lacunae, may possess different genetic backgrounds. Subjects with the ACE DD genotype could be more predisposed to be symptomatic in first-ever lacunar stroke, while the ACE II genotype may convey resistance to symptoms even after multiple lacunar strokes. Polymorphism of genes of the renin-angiotensin system could be involved in the manifestation of neurological symptoms of lacunar infarction.
authors.affiliation: Department of Geriatric Medicine, Ehime University School of Medicine, Ehime, Japan.
authors.forename: Jun-hui
authors.initials: JH
authors.lastname: Zhang
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Nakura
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Katagi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics; D000809:Angiotensins / Q000235:genetics; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D000809:Angiotensins; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A