NOTCH3 Gene Variant Identified as Stroke Risk Factor in Older Adults

January 21, 2021
A common genetic variant has been identified as a risk factor for stroke, especially in adults aged older than 65 years, according to a study published in the journal Stroke. Cerebral small vessel disease (SVD) causes about a quarter of ischaemic strokes worldwide and is the most common cause of vascular dementia. SVD is commonly associated with aging and hypertension, but a minority of cases are caused by cysteine altering variants in the NOTCH3 gene. Approximately 1 in 300 people have this type of gene variant. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is caused by this gene variant, has been associated with SVD and an increased risk of stroke. Vida Abedi, PhD, Geisinger, Danville, Pennsylvania, and colleagues evaluated a set of health records, including imaging and genomic sequencing data, of more than 300 patients. Of the patients, 118 exhibited a NOTCH3 variant. Of the 118 patients with a NOTCH3 variant, 12.6% had a history of stroke, compared with 4.9% of the patients without the variant. The risk of stroke was significantly higher in those aged older than 65 years , and patients exhibited a higher number of white matter lesions on the brain. Although all 118 patients in the study group had a NOTCH3 genetic variant, the specific variant that causes CADASIL was rarely seen. “Given the high population frequency of NOTCH3 variants, the number of individuals who may be at higher risk of SVD and stroke as a result of a NOTCH3 variant is significant,” the authors wrote. The study indicates that most individuals with a NOTCH3 variant will develop NOTCH3-associated SVD after the age of 65. “Stroke is a complex multifactorial condition,” said Dr. Abedi. “Dissecting its risk factors and identifying ways to improve patient outcomes is a crucial part of improving patient care.” “This study represents a novel and powerful approach to studying the genetic basis of neurologic disease,” said coauthor Ramin Zand, MD, Geisinger. Reference: https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031609 SOURCE: Geisinger