颅内狭窄是全球范围内最常见的卒中原因之一。几个单核苷酸多态性与颅内动脉粥样硬化有关,据推测,这是颅内大动脉狭窄(ILAS)最常见的潜在原因。我们以前在主要的亚洲队列中回顾了与ILAS相关的已知遗传变异,但它们在西方多种族人群中的患病率和在ILAS中的作用尚不确定。
我们利用了北曼哈顿研究的现有成像和遗传数据,多种族前瞻性队列研究。在文献综述的基础上,我们选择了脂联素Q(ADIPOQ)rs2241767和rs182052,无名指蛋白213(RNF213)rs112735431,载脂蛋白E(APOE)rs429358,磷酸二酯酶4D(PDE4D)rs2910829,脂蛋白脂酶(LPL)rs320和醛固酮合成酶(CYP11B2)rs999nor我们使用飞行时间磁共振血管造影(MRA)将ILAS定义为任何颅内大动脉中的管腔狭窄>50%。
我们包括1109名参与者(平均年龄70±9岁,70%的西班牙裔,60%的女性)在这项研究中。在81名(7%)NOMAS参与者中发现了ILAS。Logistic回归分析调整年龄,性别,主要成分,和血管危险因素显示,在显性模型下,ILAS患病率与CYP11B2rs1799998(OR=0.56,95CI:0.35-0.89)和LPLrs320杂合子基因型(OR=1.68,95CI:1.05-2.71)相关。ADIPOQrs2241767和rs182052,APOErs429358和CYP11B2rs1799998变体的基因型分布在非西班牙裔白人和黑人之间显着不同,和西班牙裔群体。当参与者进一步按种族/民族分层时,CYP11B2rs1799998在不同种族/族裔群体中的估计值一致,但LPLrs320的估计值不一致.
CYP11B2rs1799998变异可能是跨种族/族裔群体的ILAS的保护性遗传因素,但与LPLrs320相关的ILAS风险因种族/民族而异。进一步的功能研究可能有助于阐明这些变体在ILAS病理生理学中的作用。
Intracranial stenosis is one of the most common causes of stroke worldwide. Several single nucleotide polymorphisms have been associated with intracranial atherosclerosis, which is inferred to be the most common underlying cause of intracranial large artery stenosis (ILAS). We previously reviewed known genetic variants related to ILAS in predominantly Asian cohorts, but their prevalence and role in ILAS among western multiethnic populations are uncertain.
We leveraged existing imaging and genetic data from the Northern Manhattan Study, a multiethnic prospective cohort study. Based on literature review, we selected adiponectin Q (ADIPOQ) rs2241767 and rs182052, ring finger protein 213 (RNF213) rs112735431, apolipoprotein E (APOE) rs429358, phosphodiesterase 4D (PDE4D) rs2910829, lipoprotein lipase (LPL) rs320, and aldosterone synthase (CYP11B2) rs1799998 variants as candidates to explore. We defined ILAS as luminal stenosis >50% in any intracranial large artery using time-of-flight magnetic resonance angiography (MRA).
We included 1109 participants (mean age 70 ± 9 years, 70% Hispanic, 60% women) in this study. ILAS was identified in 81 (7%) NOMAS participants. Logistic regression analyses adjusted for age, sex, principal components, and vascular risk factors showed ILAS prevalence associated with CYP11B2 rs1799998 under the dominant model (OR = 0.56, 95%CI: 0.35-0.89) and LPL rs320 heterozygote genotype (OR = 1.68, 95%CI: 1.05-2.71). The genotype distributions of ADIPOQ rs2241767 and rs182052, APOE rs429358 and CYP11B2 rs1799998 variants were significantly different among non-Hispanic white and Black, and Hispanic groups. When participants were further stratified by race/ethnicity, the estimates were consistent for CYP11B2 rs1799998 across race/ethnic groups but not for LPL rs320.
The CYP11B2 rs1799998 variant may be a protective genetic factor for ILAS across race/ethnic groups, but the risk of ILAS associated with LPL rs320 varies by race/ethnic group. Further functional studies may help elucidate the role that these variants play in the pathophysiology of ILAS.