Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

Takaaki Morimoto, Yohei Mineharu, Koh Ono, Masahiro Nakatochi, Sahoko Ichihara, Risako Kabata, Yasushi Takagi, Yang Cao, Lanying Zhao, Hatasu Kobayashi, Kouji H. Harada, Katsunobu Takenaka, Takeshi Funaki, Mitsuhiro Yokota, Tatsuaki Matsubara, Ken Yamamoto, Hideo Izawa, Takeshi Kimura, Susumu Miyamoto, Akio Koizumi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. Methods and results: We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). Conclusions: The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

Original languageEnglish
Article numbere0175649
JournalPloS one
Volume12
Issue number4
DOIs
Publication statusPublished - 01-04-2017

Fingerprint

Fingers
Coronary Artery Disease
Genes
odds ratio
risk factors
genes
Odds Ratio
Moyamoya Disease
confidence interval
Confidence Intervals
Genome
cerebrovascular disorders
Population
Cerebrovascular Disorders
genome
smoking (habit)
coronary artery disease
Sex Ratio
hyperlipidemia
Dyslipidemias

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Morimoto, T., Mineharu, Y., Ono, K., Nakatochi, M., Ichihara, S., Kabata, R., ... Koizumi, A. (2017). Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease. PloS one, 12(4), [e0175649]. https://doi.org/10.1371/journal.pone.0175649
Morimoto, Takaaki ; Mineharu, Yohei ; Ono, Koh ; Nakatochi, Masahiro ; Ichihara, Sahoko ; Kabata, Risako ; Takagi, Yasushi ; Cao, Yang ; Zhao, Lanying ; Kobayashi, Hatasu ; Harada, Kouji H. ; Takenaka, Katsunobu ; Funaki, Takeshi ; Yokota, Mitsuhiro ; Matsubara, Tatsuaki ; Yamamoto, Ken ; Izawa, Hideo ; Kimura, Takeshi ; Miyamoto, Susumu ; Koizumi, Akio. / Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease. In: PloS one. 2017 ; Vol. 12, No. 4.
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abstract = "Background: The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. Methods and results: We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04{\%} vs. 0.98{\%}), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95{\%} confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95{\%} confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95{\%} confidence interval: 0.87-16.77; p = 0.076). Conclusions: The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.",
author = "Takaaki Morimoto and Yohei Mineharu and Koh Ono and Masahiro Nakatochi and Sahoko Ichihara and Risako Kabata and Yasushi Takagi and Yang Cao and Lanying Zhao and Hatasu Kobayashi and Harada, {Kouji H.} and Katsunobu Takenaka and Takeshi Funaki and Mitsuhiro Yokota and Tatsuaki Matsubara and Ken Yamamoto and Hideo Izawa and Takeshi Kimura and Susumu Miyamoto and Akio Koizumi",
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Morimoto, T, Mineharu, Y, Ono, K, Nakatochi, M, Ichihara, S, Kabata, R, Takagi, Y, Cao, Y, Zhao, L, Kobayashi, H, Harada, KH, Takenaka, K, Funaki, T, Yokota, M, Matsubara, T, Yamamoto, K, Izawa, H, Kimura, T, Miyamoto, S & Koizumi, A 2017, 'Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease', PloS one, vol. 12, no. 4, e0175649. https://doi.org/10.1371/journal.pone.0175649

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease. / Morimoto, Takaaki; Mineharu, Yohei; Ono, Koh; Nakatochi, Masahiro; Ichihara, Sahoko; Kabata, Risako; Takagi, Yasushi; Cao, Yang; Zhao, Lanying; Kobayashi, Hatasu; Harada, Kouji H.; Takenaka, Katsunobu; Funaki, Takeshi; Yokota, Mitsuhiro; Matsubara, Tatsuaki; Yamamoto, Ken; Izawa, Hideo; Kimura, Takeshi; Miyamoto, Susumu; Koizumi, Akio.

In: PloS one, Vol. 12, No. 4, e0175649, 01.04.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

AU - Morimoto, Takaaki

AU - Mineharu, Yohei

AU - Ono, Koh

AU - Nakatochi, Masahiro

AU - Ichihara, Sahoko

AU - Kabata, Risako

AU - Takagi, Yasushi

AU - Cao, Yang

AU - Zhao, Lanying

AU - Kobayashi, Hatasu

AU - Harada, Kouji H.

AU - Takenaka, Katsunobu

AU - Funaki, Takeshi

AU - Yokota, Mitsuhiro

AU - Matsubara, Tatsuaki

AU - Yamamoto, Ken

AU - Izawa, Hideo

AU - Kimura, Takeshi

AU - Miyamoto, Susumu

AU - Koizumi, Akio

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background: The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. Methods and results: We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). Conclusions: The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

AB - Background: The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. Methods and results: We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). Conclusions: The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

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U2 - 10.1371/journal.pone.0175649

DO - 10.1371/journal.pone.0175649

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JF - PLoS One

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