Bin Zhu1, Xingju Liu2,3,4, Xueke Zhen5, Xixi Li1, Mingfen Wu1, Yan Zhang2,3,4, Zhigang Zhao1, Dong Zhang2,3,4, Jizong Zhao2,3,4. 1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. China National Clinical Research Center for Neurological Diseases, Beijing, China. 4. Center of Stroke, Beijing Institute for Brain Disorder, Beijing, China. 5. Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China.
Abstract
BACKGROUND: Gene polymorphism especially Ring Finger Protein 213 (RNF213) p.R4810K is one of the main cause of moyamoya disease (MMD) in Asian populations, especially among Japanese people. However, missense mutation may not explain the reduced frequency of MMD in Chinese patients. We performed a hospital based case-control study in a Chinese population to elucidate the possible underlying reasons. METHODS: Five gene polymorphism loci, namely, rs35692831, rs9916351, rs9913636, rs8074015 and rs112735431, were included. A total of 98 patients and 114 healthy controls were enrolled in the study. Genomic DNA was genotyped by Mass Array methods. RESULTS: A significant difference was observed between patients and healthy controls in rs9916351, rs9913636, and rs8074015 loci under three genotypes and allelic models (P<0.01). Logistic regression analysis revealed the significant differences under the dominant, recessive and additional model in rs9916351 [odds ratio (OR) =4.173, 95% confidence interval (CI): 2.290-7.606, P<0.001; OR =3.152, 95% CI: 1.585-6.267, P=0.001; OR =0.199, 95% CI: 1.727-3.764, P<0.001; respectively] and rs8074015 (OR =0.359, 95% CI: 0.206-0.627, P<0.001; OR =0.348, 95% CI: 0.148-0.81, P=0.015; OR =0.208, 95% CI: 0.311-0.703, P<0.001; respectively), even adjusting for age and gender. In addition, the haplotype rs9913636-rs8074015 under "GACG" showed significant association with MMD. CONCLUSIONS: Our results had revealed the polymorphism of RNF213 rs9916351 and rs8074015 were significantly associated with MMD especially in Chinese population. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Gene polymorphism especially Ring Finger Protein 213 (RNF213) p.R4810K is one of the main cause of moyamoya disease (MMD) in Asian populations, especially among Japanese people. However, missense mutation may not explain the reduced frequency of MMD in Chinese patients. We performed a hospital based case-control study in a Chinese population to elucidate the possible underlying reasons. METHODS: Five gene polymorphism loci, namely, rs35692831, rs9916351, rs9913636, rs8074015 and rs112735431, were included. A total of 98 patients and 114 healthy controls were enrolled in the study. Genomic DNA was genotyped by Mass Array methods. RESULTS: A significant difference was observed between patients and healthy controls in rs9916351, rs9913636, and rs8074015 loci under three genotypes and allelic models (P<0.01). Logistic regression analysis revealed the significant differences under the dominant, recessive and additional model in rs9916351 [odds ratio (OR) =4.173, 95% confidence interval (CI): 2.290-7.606, P<0.001; OR =3.152, 95% CI: 1.585-6.267, P=0.001; OR =0.199, 95% CI: 1.727-3.764, P<0.001; respectively] and rs8074015 (OR =0.359, 95% CI: 0.206-0.627, P<0.001; OR =0.348, 95% CI: 0.148-0.81, P=0.015; OR =0.208, 95% CI: 0.311-0.703, P<0.001; respectively), even adjusting for age and gender. In addition, the haplotype rs9913636-rs8074015 under "GACG" showed significant association with MMD. CONCLUSIONS: Our results had revealed the polymorphism of RNF213 rs9916351 and rs8074015 were significantly associated with MMD especially in Chinese population. 2020 Annals of Translational Medicine. All rights reserved.
Authors: Adam J Kundishora; Samuel T Peters; Amélie Pinard; Daniel Duran; Shreyas Panchagnula; Tanyeri Barak; Danielle F Miyagishima; Weilai Dong; Hannah Smith; Jack Ocken; Ashley Dunbar; Carol Nelson-Williams; Shozeb Haider; Rebecca L Walker; Boyang Li; Hongyu Zhao; Dean Thumkeo; Arnaud Marlier; Phan Q Duy; Nicholas S Diab; Benjamin C Reeves; Stephanie M Robert; Nanthiya Sujijantarat; Amber N Stratman; Yi-Hsien Chen; Shujuan Zhao; Isabelle Roszko; Qiongshi Lu; Bo Zhang; Shrikant Mane; Christopher Castaldi; Francesc López-Giráldez; James R Knight; Michael J Bamshad; Deborah A Nickerson; Daniel H Geschwind; Shih-Shan Lang Chen; Phillip B Storm; Michael L Diluna; Charles C Matouk; Darren B Orbach; Seth L Alper; Edward R Smith; Richard P Lifton; Murat Gunel; Dianna M Milewicz; Sheng Chih Jin; Kristopher T Kahle Journal: JAMA Neurol Date: 2021-08-01 Impact factor: 29.907