气候变化领域集成服务门户(CCPortal): Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population

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DOI	10.1073/pnas.2004199118
	Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population
	Penova M.; Kawaguchi S.; Yasunaga J.-I.; Kawaguchi T.; Sato T.; Takahashi M.; Shimizu M.; Saito M.; Tsukasaki K.; Nakagawa M.; Takenouchi N.; Hara H.; Matsuura E.; Nozuma S.; Takashima H.; Izumo S.; Watanabe T.; Uchimaru K.; Iwanaga M.; Utsunomiya A.; Tabara Y.; Paul R.; Yamano Y.; Matsuoka M.; Matsuda F.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genomewide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10-9) and class II (P = 1.21 × 10-8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLAC∗ 07:02 (P = 2.61 × 10-5), HLA-B∗07:02 (P = 4.97 × 10-10), HLADRB1∗ 01:01 (P = 1.15 × 10-9) and HLA-DQB1∗05:01 (P = 2.30 × 10-9) were associated with disease risk, while HLA-B∗40:06 (P = 3.03 × 10-5), HLA-DRB1∗15:01 (P = 1.06 × 10-5) and HLA-DQB1∗06:02 (P = 1.78 × 10-6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10-10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/ TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Genome-wide association study; HAM/TSP; HLA; HTLV-1; Proviral load
语种	英语
scopus关键词	HLA A antigen; HLA DPB1 antigen; HLA DQB1 antigen; HLA DRB1 antigen; leucine; proline; Article; asymptomatic disease; controlled study; disease carrier; DNA determination; DPB1 gene; DQB1 gene; DRB1 gene; gene; gene frequency; genetic association; genetic identification; genetic marker; genetic risk; genetic susceptibility; genome-wide association study; genotype; high throughput sequencing; HLA A gene; HLA B gene; HLA C gene; human; Human T-lymphotropic virus 1; Japanese (people); major clinical study; priority journal; risk factor; tropical spastic paraparesis; virus load
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180298
作者单位	Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606-8507, Japan; Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan; Department of Microbiology, Kawasaki Medical School, Kurashiki, Okayama, 701-0192, Japan; Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, Saitama, 350-1298, Japan; Department of Neurology, Kyoto Prefectural University, Medicine Graduate School of Medical Science, Kamigyo-ku, Kyoto, 602-8566, Japan; Department of Microbiology, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan; Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, 849-8501, Japan; Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical an...
推荐引用方式 GB/T 7714	Penova M.,Kawaguchi S.,Yasunaga J.-I.,et al. Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population[J],2021,118(11).
APA	Penova M..,Kawaguchi S..,Yasunaga J.-I..,Kawaguchi T..,Sato T..,...&Matsuda F..(2021).Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Penova M.,et al."Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).