Does the RNF213 p.R4810K variant increase the risk of intracranial atherosclerotic disease in patients with acute ischemic stroke or TIA, and is this risk modified by obesity?
The RNF213 p.R4810K variant is associated with an increased risk of intracranial atherosclerotic disease, particularly in the anterior circulation, and this risk is synergistically amplified by obesity.
RNF213 p.R4810K (rs112735431) was performed using the Melt Analysis of Mis-match Amplification Mutation Assays. 5 Patients were classified as wild-type (G/G) or variant carriers (G/A or A/A). ICAD was defined as ≥50% stenosis or occlusion of major intracranial arteries on magnetic resonance angiography or computed tomography angiography, 6 as initially interpreted independently at each participating hospital by at least one radiologist and one stroke neurologist. For the sensitivity analysis, intracranial atherosclerotic stenosis (ICAS) was defined as ≥50% stenosis without occlusion. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals for each outcome. Exploratory interaction analyses were also conducted using multiplicative terms to assess potential effect modification by traditional atherosclerotic risk factors. Body mass index (BMI) was categorized into four groups (<18.5, 18.5–24.9, 25.0–29.9, and ≥30.0 kg/m 2 ). 7 Heterogeneity was further explored by stratifying the analyses by BMI. Patients were divided into eight subgroups based on RNF213 p.R4810K carrier status and BMI category. Interaction effects were tested by including multiplicative interaction terms in the corresponding logistic regression models.
Takashima et al. (Fri,) studied this question.