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Association of C hr17q25 with cerebral white matter hyperintensities and cognitive impairment: the J ‐ SHIPP study
Author(s) -
Tabara Y.,
Igase M.,
Okada Y.,
Nagai T.,
Uetani E.,
Kido T.,
Ochi N.,
Takita R.,
Yamamoto M.,
Kohara K.,
Miki T.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/j.1468-1331.2012.03879.x
Subject(s) - hyperintensity , medicine , asymptomatic , white matter , cardiology , magnetic resonance imaging , locus (genetics) , genotype , brain structure and function , cognition , genetics , psychiatry , biology , radiology , gene
Background and purpose A recent genome‐wide association study has successfully identified several genetic variations in the C hr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non‐ E uropean origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function. Methods Study subjects were 1190 general J apanese persons (66.0 ± 8.9 years old). Asymptomatic cerebrovascular damage, including lacunar infarctions, microbleeds, periventricular hyperintensity and deep and subcortical white matter hyperintensity ( DSWMH ), was evaluated by brain magnetic resonance imaging. Results A polymorphism rs3744028 was significantly associated with DSWMH grade ( P = 0.015) but not periventricular hyperintensity, lacunar infarction, and microbleeds. Although age, hypertension, insulin resistance, B ‐type natriuretic peptide, and carotid atherosclerosis were also correlated with DSWMH , association of the genotype was independent of these environmental risk factors. In contrast, the risk allele had a protective effect against reduced cognitive function. Conclusion Susceptibility of the 17q25 locus may be conserved beyond ethnic differences. Genetic variants may have bipolar effects on brain histological and functional changes.