GJA1 Gene Polymorphisms and Topographic Distribution of Cranial MRI Lesions in Cerebral Small Vessel Disease.

Jing Zhang,Junlong Shu,Meng Yu,Qiang Gang,Wei Zhang,Qian You,Yining Huang,Haiqiang Jin,Wei Sun

doi:10.3389/fneur.2020.583974

Abstract

Vascular endothelial cell (EC) and blood–brain barrier (BBB) dysfunction is the core pathogenesis of cerebral small vessel disease (CSVD). Moreover, animal experiments have shown the importance of connexin (Cx)-43 in EC and BBB function. In this study, we recruited 200 patients diagnosed with sporadic CSVD. Initially, we examined imaging scores of white matter hyperintensities (WMH), lacunar infarction (LI), and cerebral microbleeds (CMB). Additionally, we performed next-generation sequencing of the GJA1 gene (Cx43 coding gene) to examine correlation between these single-nucleotide polymorphisms and the burden and distribution of CSVD. Fourteen target loci were chosen. Of these, 13 loci (92.9%) contributed toward risk for cerebellar LI, one locus (7.1%) was shown to be a protective factor for lobar CMB after FDR adjustment. In conclusion, single-nucleotide polymorphisms in the GJA1 gene appear to affect the distribution but not severity of CSVD.

Highlights

Cerebral small vessel disease (CSVD) affects the small arteries, arterioles, venules, and capillaries of the brain, and describes a group of clinical, pathological, and neuroimaging processes of heterogeneous etiologies [1]
We focused on the impact of Cx43 in cerebral small vessel disease (CSVD) mainly because Cx43 is highly expressed in vascular endothelial cell (EC) and ECs in the BBB, as well as astrocytes and pericytes forming the BBB [10]
We have shown that GJA1 gene single-nucleotide polymorphisms (SNPs) correlate with magnetic resonance imaging (MRI) features of CSVD

Summary

Introduction

Cerebral small vessel disease (CSVD) affects the small arteries, arterioles, venules, and capillaries of the brain, and describes a group of clinical, pathological, and neuroimaging processes of heterogeneous etiologies [1]. White matter hyperintensities (WMH), lacunar infarctions (LI), and cerebral microbleeds (CMB) are the three major neuroimaging features of CSVD [2]. In the most common inherited CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), WMH tend to be located in the capsula externa and temporal pole [3]. With age-related WMH, the lesions tend to involve the frontal lobes. These findings suggest that spatial specificity may provide insight into the underlying vascular pathology and disease mechanisms [4]

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Results

Discussion

Conclusion