Association of NOTCH3 Gene Polymorphisms with Ischemic Stroke and Its Subtypes: A Meta-Analysis

Abstract

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05).

Headache and NOTCH3 Gene Variants in Patients with CADASIL

“…The results of these types of studies are varied. Keat Wei et al [ 69 ] and González-Giraldo et al [ 70 ] concluded that this mild variant probably does not play a major role in the pathogenesis of CADASIL. He concluded that due to the high prevalence of this variant in the general population, it does not affect the further development of CADASIL in patients suffering from headaches.…”

Potential Key Genes Associated with Stroke types and its subtypes: A Computational Approach

“…Emerging evidences from published meta-analysis and GWAS studies suggests that several genetic variants (MTHFR, MMP9, PDE4D, CYP4A11, ALOX5P, NOTCH, NINJ2, FGB, eNOS, PITX2, ZFHX3, HDAC9, ABO, etc) have been identified, even though the extent of the effect of each variant is regarded as inter-varying within different populations including Asian, Caucasian, African. [1,1,7,14,[35][36][37][38][39][39][40][41][42][43][44] The findings, however, are often unclear and hard to interpret. Genetic association studies in diverse stroke populations negate matters of the restricted patient population by the a priori choice of a functionally relevant gene and its relation with a specific phenotype.…”

eNOS rs2070744 polymorphism might influence predisposition to hemorrhagic cerebral vascular diseases in East Asians: A meta‐analysis

“…The authors used Review Manager to pool meta‐analyses results (Version 5.3.3, The Cochrane Collaboration, Software Update). The authors calculated ORs and 95% CIs of Z test to evaluate relationship between eNOS polymorphisms and predisposition to hemorrhagic cerebral vascular diseases in dominant, recessive, overdominant, and allele models (Keat Wei, Griffiths, Irene, & Kooi, ; Wei, Griffiths, Kooi, & Irene, ). The authors set the statistical significant threshold at 0.05.…”