Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Cephalalgia. 2022 Aug;42(9):888-898. doi: 10.1177/03331024221080891. Epub 2022 Mar 18.
The role of the p.R544C variant, the predominant variant of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in multiple East Asian regions, in migraine is unknown.
Migraine patients (n = 2,884) (2,279F/605M, mean age 38.8 ± 11.7 years), including 324 (11.2%) with migraine with aura, were prospectively enrolled by headache specialists according to the International Classification of Headache Disorders criteria. These patients and 3,502 population controls free of stroke, dementia, and headache were genotyped for p.R544C by TaqMan genotyping assay or Axiom Genome-Wide TWB 2.0 Array. Clinical manifestations and brain magnetic resonance images were examined and compared between migraine patients with and without p.R544C.
Thirty-two migraine patients (1.1%) and 36 controls (1.0%) harbored the p.R544C variant, and the percentages were comparable among migraine patients without and with aura, and controls (1.2%, vs. 0.6% vs. 1.0%, p = 0.625). Overall, migraine patients with and without the p.R544C variant had similar percentages of migraine with aura, headache characteristics, frequencies and disabilities. However, those with p.R544C were less likely to have pulsatile headaches (50.0% vs. 68.2%, p = 0.028), and more likely to have moderate to severe white matter hyperintensities in the external capsule (18.8% vs. 1.2%, p = 0.006) and anterior temporal lobe (12.5% vs. 0%, p = 0.008).
Our findings suggest that p.R544C does not increase the risk of migraine with aura, or migraine as a whole, and generally does not alter clinical manifestations of migraine. The role of variants, as well as potential influences from ethnicity or modifier genes, in migraine needs to be further clarified.
p.R544C 变体是脑常染色体显性动脉病伴皮质下梗死和白质脑病在东亚多个地区的主要变体，但其在偏头痛中的作用尚不清楚。
偏头痛患者（n=2884）（2279 例女性/605 例男性，平均年龄 38.8±11.7 岁），包括 324 例（11.2%）偏头痛伴先兆，由头痛专家根据国际头痛疾病分类标准前瞻性纳入。这些患者和 3502 名无卒中、痴呆和头痛的人群对照通过 TaqMan 基因分型检测或 Axiom 全基因组 TWB 2.0 阵列进行 p.R544C 基因分型。检查偏头痛患者和无偏头痛患者的临床表现和脑磁共振图像，并进行比较。
32 例偏头痛患者（1.1%）和 36 例对照（1.0%）携带 p.R544C 变体，且无先兆偏头痛患者和有先兆偏头痛患者以及对照组的携带率相似（1.2%、0.6%和 1.0%，p=0.625）。总体而言，携带和不携带 p.R544C 变体的偏头痛患者有先兆偏头痛、头痛特征、频率和残疾的百分比相似。然而，携带 p.R544C 的患者搏动性头痛的可能性较小（50.0% vs. 68.2%，p=0.028），而在外部囊和前颞叶中更有可能出现中度至重度的脑白质高信号（18.8% vs. 1.2%和 12.5% vs. 0%，p=0.006 和 p=0.008）。
我们的研究结果表明，p.R544C 不会增加有先兆偏头痛或偏头痛的总体风险，也不会改变偏头痛的临床表现。变体的作用以及种族或修饰基因的潜在影响，在偏头痛中还需要进一步阐明。
