Carotid Intima-Media Thickness, Genetic Risk, and Ischemic Stroke: A Family-Based Study in Rural China

Abstract

Background: Carotid intima-media thickness (cIMT) has been associated with an elevated risk of ischemic stroke (IS) in several studies, but the results are inconsistent. We investigated whether the association between cIMT and IS varied across different IS subtypes, and further assessed gene–cIMT interactions’ association with IS risk. Methods: A total of 1048 IS cases (795 large-artery atherosclerosis (LAA) cases, 103 small-vessel occlusion (SVO) cases, and 150 other subtypes) and 2696 IS-free controls across 2179 families were included in the analysis. Self-reported IS cases were confirmed through medical records’ review and head imaging by computed tomography and/or magnetic resonance imaging. The mean values of the common cIMT obtained in bilateral distal and proximal carotid artery segments were used. The genotype information of rs2910164 polymorphism in microRNA-146a (miR-146a) was also collected. Results: We found that cIMT was significantly associated with a higher risk of IS and LAA subtype but not SVO subtype in the multivariate-adjusted models. The odds ratio (OR) and 95% confidence interval (CI) in the highest quartile versus the lowest quartile of cIMT was 2.48 (1.92–3.20) for IS and 2.75 (2.08–3.64) for LAA (both p trend <0.001). The results also showed that there was a significant interaction between cIMT and rs2910164 genotype with the risk of IS (p interaction = 0.03) and LAA (p interaction = 0.02). The associations of cIMT with IS and LAA were strengthened among participants carried rs2910164_GG genotype compared with those with rs2910164_CC genotype. Conclusions: Our results indicate that higher cIMT levels were significantly associated with IS and LAA subtype but not SVO subtype, and the relations were modified by rs2910164 polymorphism in miR-146a.

Association between polymorphisms in miRNAs and ischemic stroke: A meta-analysis

“…The characteristics of the included studies are presented in Table 2, classified by miRNA. HWE-deviated was found in 6 references, [31,38,40,50–52] and the others were conformed with HWE.…”

“…We yielded 234 papers initially and 22 studies, [31–52] containing 8879 cases and 12,091 controls, were included in this meta-analysis finally. Figure 1 shows the progress of study selection.…”

“…Figure 1 shows the progress of study selection. Among these studies, 17 studies focused on miR-146a G>C (rs2910164), [31,32,[34][35][36][37][38][39][40][41][43][44][45][46][47]51,52] 9 studies focused on miR-149 T>C (rs2292832), [33][34][35][42][43][44]46,49,50] 10 studies focused on miR-196a2 T>C (rs11614913), [34,[36][37][38][42][43][44]46,47,50] and 11 studies focused on miR-499 A>G (rs3746444). [34,36,38,41,43,44,[46][47][48][49]52] From the included studies, 17 were from China, 2 from Egypt, 2 from South Korea and 1 from Iran.…”

The Role of Intima-Media-Thickness, Ankle Brachial-Index, and Inflammatory Biochemical Parameters for Stroke Risk Prediction: An Update Systematic Review

“…Six studies 8,10,[14][15][16]19 suggested that increase in carotid intima-media-thickness (CIMT) was significantly associated with a higher risk of stroke. Danuaji, et al (2023) 8 found that Atherosclerotic arteries are a risk factor for acute ischemic stroke (AIS) if their carotid intima-media-thickness (CIMT) value is less than 25% or greater than 1.0 mm.…”