[1]任伟凡,辛大伟,胡劲涛,等.全外显子组测序筛选1个人类白细胞抗原-B27阴性强直性脊柱炎家系的强直性脊柱炎易感基因[J].中医正骨,2022,34(06):25-28.
 REN Weifan,XIN Dawei,HU Jintao,et al.Screening of susceptible gene to ankylosing spondylitis in a human leucocyte antigen-B27-negative family by whole exome sequencing[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2022,34(06):25-28.
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全外显子组测序筛选1个人类白细胞抗原-B27阴性强直性脊柱炎家系的强直性脊柱炎易感基因()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第34卷
期数:
2022年06期
页码:
25-28
栏目:
临床研究
出版日期:
2022-06-20

文章信息/Info

Title:
Screening of susceptible gene to ankylosing spondylitis in a human leucocyte antigen-B27-negative family by whole exome sequencing
作者:
任伟凡1辛大伟1胡劲涛2吴风晴1周化腾1杜伟斌1全仁夫1
(1.杭州市萧山区中医院,浙江 杭州 311201; 2.浙江中医药大学附属杭州市中医院,浙江 杭州 310007)
Author(s):
REN Weifan1XIN Dawei1HU Jintao2WU Fengqing1ZHOU Huateng1DU Weibin1QUAN Renfu1
1.Xiaoshan Hospital of Traditional Chinese Medicine,Hangzhou 311201,Zhejiang,China 2.Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University,Hangzhou 310007,Zhejiang,China
关键词:
脊柱炎强直性 HLA-B27抗原 易感基因 全外显子组测序
Keywords:
spondylitisankylosing HLA-B27 antigen susceptible gene whole exome sequencing
摘要:
目的:筛选1个人类白细胞抗原-B27阴性强直性脊柱炎(ankylosing spondylitis,AS)家系的AS易感基因。方法:纳入1个AS家系的15名核心成员,其中AS患者2例。采集AS家系15名核心成员的外周血,提取外周血基因组。将先证者、先证者女儿、先证者儿子的基因组进行全外显子组测序,分析测序数据,筛选AS易感基因,并采用Sanger测序验证筛选出的AS易感基因。结果:外显子组测序获得了高质量的测序数据。RELA基因10号外显子上存在一个杂合移码突变c.1039delG。Sanger测序结果显示,先证者、先证者女儿及先证者孙子的基因组上存在该突变,其他家系成员不存在该突变。结论:突变的RELA基因可能是该AS家系的AS易感基因。
Abstract:
Objective:To screen the ankylosing spondylitis(AS)-susceptibility gene in a human leucocyte antigen(HLA)-B27-negative family.Methods:Fifteen core members in an AS family were enrolled in the study,including 2 AS cases and their peripheral blood samples were collected for extracting the genomic DNA.The Whole exome sequencing(WES)was performed on proband and proband's daughter and son.The sequencing data were analyzed for screening the AS-susceptibility gene,which was verified by Sanger sequencing.Results:The high-quality sequencing data yielded via WES.A heterozygous frameshift mutation c.1039delG in exon 10 of RELA gene was observed.As revealed by Sanger sequencing,the mutation was only present in the genomes of the proband and the proband's daughter and grandson,while not present in other family members.Conclusion:The mutated RELA gene is presumably the AS-susceptibility gene in this family.

参考文献/References:

[1] LIU L,YUAN Y,ZHANG S,et al.Osteoimmunological insights into the pathogenesis of ankylosing spondylitis[J].J Cell Physiol,2021,236(9):6090-6100.
[2] O'RIELLY D D,UDDIN M,RAHMAN P.Ankylosing spondylitis:beyond genome-wide association studies[J].Curr Opin Rheumatol,2016,28(4):337-345.
[3] LIN H,GONG Y Z.Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis:a meta-analysis[J].Rheumatol Int,2017,37(8):1267-1280.
[4] AKKOC N,YARKAN H,KENAR G,et al.Ankylosing spondylitis:HLA-B*27-positive versus HLA-B*27-negative disease[J].Curr Rheumatol Rep,2017,19(5):26.
[5] UDDIN M,MAKSYMOWYCH W P,INMAN R,et al.UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family[J].BMC Genet,2013,14:67.
[6] VAN DER LINDEN S,VALKENBURG H A,CATS A.Evalu-ation of diagnostic criteria for ankylosing spondylitis.A proposal for modification of the New York criteria[J].Arthritis Rheum,1984,27(4):361-368
[7] DOUGADOS M,VAN DER LINDEN S,JUHLIN R,et al.The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy[J].Arthritis Rheum,1991,34(10):1218-1227.
[8] 韩仁芳,陈梦雅,刘瑞,等.强直性脊柱炎2261例流行特征及功能状态现状分析[J].安徽医药,2017,21(1):73-77.
[9] QIAN Q,XU X,HE H,et al.Clinical patterns and characteristics of ankylosing spondylitis in China[J].Clin Rheumatol,2017,36(7):1561-1568.
[10] 冀肖健,孙锴,胡拯源,等.强直性脊柱炎患者人类白细胞抗原-B27分子携带状态临床对比研究:基于脊柱关节炎智能移动管理系统的真实世界数据[J].中华内科杂志,2018,57(3):179-184.
[11] XIONG J,CHEN J,TU J,et al.Association of HLA-B27 status and gender with sacroiliitis in patients with ankylosing spondylitis[J].Pak J Med Sci,2014,30(1):22-27.
[12] REYNOLDS T L,KHAN M A,VAN DER LINDEN S,et al.Differences in HLA-B27 positive and negative patients with ankylosing spondylitis:study of clinical disease activity and concentrations of serum IgA,C reactive protein,and haptoglobin[J].Ann Rheum Dis,1991,50(3):154-157.
[13] HOMS H C,STARK L A.The NF-κB nucleolar stress response pathway[J].Biomedicines,2021,9(9):1082.
[14] HAYDEN M S,GHOSH S.NF-κB,the first quarter-century:remarkable progress and outstanding questions[J].Genes & Development,2012,26(3):203-234.
[15] 任伟凡,胡劲涛,高炀,等.强直性脊柱炎一家系全外显子组测序分析[J].中国骨伤,2020,33(7):672-676.
[16] 张贻强,祝星宇,王艳宏,等.天然药物基于核转录因子κB信号通路抗类风湿性关节炎的机制研究[J].中国药房,2019,30(7):1004-1008.
[17] 赵玉霞,梅红,彭罕鸣,等.白细胞介素38通过核因子-κB与信号转导及转录激活因子3信号通路抑制儿童炎症性肠病的分子机制[J].中华消化杂志,2019,39(4):237-243.
[18] 王洪武,邓超,蔡兴俊.烟草烟雾暴露对哮喘小鼠肺组织NF-κB p65表达的影响[J].中国热带医学,2019,19(11):1018-1021.
[19] LI Q,VERMA I M.NF-κB regulation in the immune system[J].Nat Rev Immunol,2002,2(10):725-734.
[20] PASPARAKIS M.Regulation of tissue homeostasis by NF-κB signalling:implications for inflammatory diseases[J].Nat Rev Immunol,2009,9(11):778-788.
[21] MULERO M C,HUXFORD T,GHOSH G.NF-κB,IκB,and IKK:Integral Components of Immune System Signaling[J].Adv Exp Med Biol,2019,1172:207-226.
[22] 韩飞,尤欣,唐福林.核因子κB在类风湿关节炎滑膜组织中的表达与意义[J].中华风湿病学杂志,2004,8(3):143-146.
[23] 方利,刘健,朱福兵,等.基于细胞因子/NF-κB信号通路探讨强直性脊柱炎患者血瘀状态形成的机制[J].中华中医药学刊,2016,34(12):2913-2917.
[24] SIMMONDS R E,FOXWELL B M.Signalling,inflammation and arthritis:NF-kappaB and its relevance to arthritis and inflammation[J].Rheumatology,2008,47(5):584-590.
[25] MARTIN-MILLAN M,ALMEIDA M,AMBROGINI E,et al.The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone[J].Mol Endocrinol,2010,24(2):323-334.
[26] MCDONALD M M,KIM A S,MULHOLLAND B S,et al.New insights into osteoclast biology[J/OL].JBMR Plus,2021,5(9)[2021-06-09].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441501/.
[27] LIN Z,BEI J X,SHEN M,et al.A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis[J].Nat Genet,2011,44(1):73-77.
[28] EVANS D M,SPENCER C C,POINTON J J,et al.Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility[J].Nat Genet,2011,43(8):761-767.
[29] LI Z,AKAR S,YARKAN H,et al.Genome-wide associ-ation study in Turkish and Iranian populations identify rare familial Mediterranean fever gene(MEFV)polymorphisms associated with ankylosing spondylitis[J/OL].PLoS Genet,2019,15(4)[2021-06-09].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467421/.
[30] JUNG S H,YIM S H,HU H J,et al.Genome-wide copy number variation analysis identifies deletion variants associated with ankylosing spondylitis[J].Arthritis Rheumatol,2014,66(8):2103-2112.
[31] LIU J J,FAN L L,CHEN J L,et al.A novel variant inTBX20(p.D176N)identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect[J].J Zhejiang Univ Sci B,2014,15(9):830-837.
[32] MANOLIO T A,COLLINS F S,COX N J,et al.Finding the missing heritability of complex diseases[J].Nature,2009,461(7265):747-753.

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备注/Memo

备注/Memo:
基金项目:浙江省中医药科技计划项目(2018ZB111) 通讯作者:全仁夫 E-mail:quanrenfu@126.com
更新日期/Last Update: 1900-01-01