Notch3 gene polymorphism and ischaemic cerebrovascular disease

doi:10.1136/jnnp.72.3.382

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Notch3 gene polymorphism and ischaemic cerebrovascular disease

D Ito¹, N Tanahashi¹, M Murata²^,3, H Sato¹, I Saito⁴, K Watanabe², Y Fukuuchi¹

¹ Department of Neurology, School of Medicine, Keio University, Tokyo, Japan
² Department of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan
³ Department of Hematology, School of Medicine, Keio University, Tokyo, Japan
⁴ Health Center, School of Medicine, Keio University, Tokyo, Japan

Correspondence to:
Correspondence to:
Dr D Ito, Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan;
di49{at}med.keio.ac.jp

ABSTRACT
Cerebral autosomal dominant arteriopathy with subcortical infarctsand leukoencephalopathy (CADASIL) is a type of hereditary strokeand dementia. More than 90% of patients with CADASIL have mutationsin the Notch3 gene. All mutations either create or destroy acysteine residue in the epidermal growth factor-like repeats.In addition, five polymorphisms, which lead to amino acid substitutions,have been identified within the Notch3 coding sequence. However,whether these polymorphisms affect Notch signalling or are involvedin cerebrovascular diseases is unknown. In the present study,we investigated a possible association between a T6746C polymorphismin the Notch3 coding region and the occurrence of symptomaticischaemic cerebrovascular disease (CVD) was investigated. Twohundred and thirty five patients with CVD, as confirmed by brainCT or MRI, and 315 age and sex matched control subjects wereanalyzed for genotype frequencies of the T6746C polymorphismin Notch3. The genotype distributions were: patients with CVD,C/C 14.0%, C/T 45.5%, and T/T 40.4%; controls, C/C, 14.3%; C/T,47.9%; T/T, 37.8%. The Japanese population has a higher C allelefrequency of the T6746C polymorphism than European populations.There was no significant difference between the T6746C polymorphismin patients with CVD and controls ( ${chi}$ ²=0.414, p=0.813). This wasconfirmed by the results of multiple logistic regression analysisincluding established risk factors ( ${chi}$ ² =4.65, p=0.311). In conclusion,the results indicate that T6746C polymorphism in the intracellulardomain of the Notch3 gene is not associated with an increasedrisk for CVD.

Keywords: stroke; risk factors; CADASIL; genotype

Abbreviations: CADASIL, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CVD, cerebrovascular disease; EGF, epidermal growth factor; TIA, transient ischaemic attack; PCR, polymerase chain reaction

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