Association of Chr17q25 with cerebral white matter hyperintensities and cognitive impairment: the J-SHIPP study

Authors


Correspondence: Yasuharu Tabara, Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Shogoinkawaramachi 53, Sakyo-ku, Kyoto 606-8507, Japan

(tel.: +81 75 366 7407; fax: +81 75 751 4167; e-mail: tabara@genome.med.kyotou.ac.jp; yasuharu.tabara@gmail.com).

Abstract

Background and purpose

A recent genome-wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non-European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function.

Methods

Study subjects were 1190 general Japanese 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.

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