title: NINJ2 SNP may affect the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions.
abstract: BACKGROUND
  To investigate if single nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 would be associated with earlier-onset (vs. late-onset) first-ever ischemic stroke and increase silent cerebrovascular lesions prior to the manifestation of the stroke.
  
  
  METHODS
  We prospectively enrolled 164 patients (67.6 ± 12.9 years, 92 men) admitted with first-ever ischemic strokes. All patients underwent genotyping of rs11833579 and rs12425791 as well as systemic investigations including magnetic resonance (MR) imaging and other vascular workup. Stroke-related MR lesions were registered on a brain-template-set using a custom-built software package 'Image_QNA': high-signal-intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery (FLAIR) MR images, and low signal intensity hemorrhagic lesions on gradient-echo MR images.
  
  
  RESULTS
  The rs11833579 A/A or G/A genotype was independently associated with the first-ever ischemic stroke before the age 59 vs. 59 or over, after adjusting for cardiovascular risk factors and prior medication of antiplatelet or anticoagulant drugs, increasing the risk by about 2.5 fold. In the quantitative MR lesion maps from age-sex matched subgroups (n = 124 or 126), there was no difference between the patients with the rs11833579 A/A or G/A genotype and those with the G/G genotype. Unexpectedly, the extent of leukoaraiosis on FLAIR-MR images tended to be smaller in the corona radiata and centrum semiovale of the patients with the rs12425791 A/A or G/A genotype than in those with the G/G genotype (P = 0.052). Neither the rs11833579 nor the rs12425791 genotype significantly affected initial stroke severity; however the latter was associated with relatively low modified Rankin scale scores at 1 year after stroke.
  
  
  CONCLUSIONS
  The rs11833579 A/A or G/A genotype may bring forward the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions prior to the stroke. Further studies are required to confirm our preliminary findings.
authors.affiliation: Department of Neurology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea. kdongeog@duih.org
authors.forename: Dong-Eog
authors.initials: DE
authors.lastname: Kim
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Noh
authors.forename: Sang-Wuk
authors.initials: SW
authors.lastname: Jeong
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Cha
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002545:Brain Ischemia / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000150:complications*; D017352:Echo-Planar Imaging; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000453:epidemiology / Q000235:genetics*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C504206:NINJ2 protein, human