Atherosclerosis · 2023
Association of thyroid peroxidase antibody with the RNF213 p.R4810K variant in ischemic stroke/transient ischemic attack.
СтатьяНаблюдательное исследованиеМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Yoshimoto Takeshi, Ishiyama Hiroyuki, Hattori Yorito, Nishimura Kunihiro, Okada Yoko, Watanabe Hideaki, Ohyagi Yasumasa, Akaiwa Yasuhisa, Miyamoto Tomoyuki, Kawamoto Michi, Ichijo Masahiko, Inoue Hiroyasu, Matsukawa Noriyuki, Mizuno Toshiki, Matsuyama Hirofumi, Tomimoto Hidekazu, Kawakami Daisuke, Toyoda Kazunori, Koga Masatoshi, Ihara Masafumi
Аннотация
BACKGROUND AND AIMS: RNF213 is a susceptibility gene for moyamoya disease and vasospastic angina, with a second hit considered necessary for their development. Elevated thyroid peroxidase antibody (TPO-Ab) levels have been observed in both diseases, suggesting a possible role of TPO-Ab as a second hit for developing RNF213-related vasculopathy. We investigated the association of TPO-Ab levels with RNF213-related ischemic stroke (IS)/transient ischemic attack (TIA), other than moyamoya disease.
METHODS: From the National Cerebral and Cardiovascular Center Genome Registry, a multicenter, prospective, observational study, we enrolled patients with IS/TIA who were admitted within 1 week of onset. Patients with IS/TIA due to definite moyamoya disease or hemorrhagic stroke were excluded. Participants underwent genotyping for RNF213 p. R4810K, and baseline characteristics and TPO-Ab levels were compared between RNF213 p. R4810K variant carriers and non-carriers.
RESULTS: In total, 2090 IS/TIA patients were analyzed [733 women (35.1%); median age 74 (interquartile range, 63-81) years, baseline NIHSS score 3 (2-6)], and 85 (4.1%) of them carried the variant. Median TPO-Ab levels were significantly higher in variant carriers (8.5 IU/mL vs. 2.1 IU/mL, p < 0.01), who also showed a higher frequency of elevated TPO-Ab levels (>16 IU/mL) (27.1% vs. 4.4%). In the multivariate analysis, presence of the RNF213 p. R4810K variant (adjusted odds ratio, 12.42; 95% confidential interval, 6.23-24.75) was significantly associated with elevated TPO-Ab levels.
CONCLUSIONS: Elevated TPO-Ab levels may be significantly associated with presence of the RNF213 p. R4810K variant in IS/TIA patients. Thus, TPO-Ab may inherently modify IS/TIA development in RNF213 p. R4810K variant carriers.
METHODS: From the National Cerebral and Cardiovascular Center Genome Registry, a multicenter, prospective, observational study, we enrolled patients with IS/TIA who were admitted within 1 week of onset. Patients with IS/TIA due to definite moyamoya disease or hemorrhagic stroke were excluded. Participants underwent genotyping for RNF213 p. R4810K, and baseline characteristics and TPO-Ab levels were compared between RNF213 p. R4810K variant carriers and non-carriers.
RESULTS: In total, 2090 IS/TIA patients were analyzed [733 women (35.1%); median age 74 (interquartile range, 63-81) years, baseline NIHSS score 3 (2-6)], and 85 (4.1%) of them carried the variant. Median TPO-Ab levels were significantly higher in variant carriers (8.5 IU/mL vs. 2.1 IU/mL, p < 0.01), who also showed a higher frequency of elevated TPO-Ab levels (>16 IU/mL) (27.1% vs. 4.4%). In the multivariate analysis, presence of the RNF213 p. R4810K variant (adjusted odds ratio, 12.42; 95% confidential interval, 6.23-24.75) was significantly associated with elevated TPO-Ab levels.
CONCLUSIONS: Elevated TPO-Ab levels may be significantly associated with presence of the RNF213 p. R4810K variant in IS/TIA patients. Thus, TPO-Ab may inherently modify IS/TIA development in RNF213 p. R4810K variant carriers.