白塞氏综合征中 HLA-B 基因的甲基化和表达:表观遗传学在发病机制中的潜在作用。

IF 3.4 4区 医学 Q2 RHEUMATOLOGY Clinical and experimental rheumatology Pub Date : 2024-10-01 Epub Date: 2024-01-24 DOI:10.55563/clinexprheumatol/1sf43v
Merve Özkılınç Önen, Elif Everest, Turna Demirci, Pelinsu Köprülü Şen, Esra Kızıltepe Kısakesen, Yeşim Özgüler, Sinem Nihal Esatoğlu, Emire Seyahi, Eda Tahir Turanlı
{"title":"白塞氏综合征中 HLA-B 基因的甲基化和表达:表观遗传学在发病机制中的潜在作用。","authors":"Merve Özkılınç Önen, Elif Everest, Turna Demirci, Pelinsu Köprülü Şen, Esra Kızıltepe Kısakesen, Yeşim Özgüler, Sinem Nihal Esatoğlu, Emire Seyahi, Eda Tahir Turanlı","doi":"10.55563/clinexprheumatol/1sf43v","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The HLA-B51 locus has the strongest association with Behçet's syndrome (BS). The presence of a CpG island in the HLA-B gene led us to examine the role of epigenetic regulation in BS.</p><p><strong>Methods: </strong>HLA-B51 genotyping was performed via sequence-specific PCR in 15 index familial BS cases, 17 affected relatives, 26 unaffected relatives, 46 sporadic BS cases, and 41 healthy controls. HLA-B methylation level was determined using the Zymo OneStep qMethyl kit, and HLA-B51 mRNA level was assessed by quantitative real-time PCR in 14 index familial BS cases, 15 affected relatives, 15 unaffected relatives, 11 sporadic BS cases, and 10 healthy controls.</p><p><strong>Results: </strong>HLA-B51 carrier ratio was 13/15 in index familial cases, 13/17 in affected relatives, 22/26 in unaffected relatives, 8/25 in healthy controls, and 35/47 in sporadic BS cases. HLA-B51 expression level in HLA-B51+ BS cases was 2.2-fold higher than in their unaffected relatives (p=0.0149) and 1.3-fold higher than in healthy controls (p=0.0188), while sporadic BS cases had a 2.7-fold higher level than healthy controls (p=0.0487). HLA-B promoter methylation was significantly lower in HLA-B51+ familial BS cases than in unaffected relatives (0.4-fold, p=0.01), affected relatives (0.36-fold, p=0.0219), and healthy controls (0.34-fold, p=0.0371) and slightly lower in HLA-B51+ sporadic BS cases than in healthy controls (0.71-fold, p=0.2347). There was an inverse correlation between HLA-B promoter methylation and HLA-B51 expression in HLA-B51+ sporadic BS cases (p=0.0164).</p><p><strong>Conclusions: </strong>This study indicates epigenetic involvement associated with the HLA-B51 locus in BS, both in familial and sporadic cases. Further studies with larger sample sizes are needed to confirm our results.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HLA-B gene methylation and expression in Behçet's syndrome: a potential role of epigenetics in the pathogenesis.\",\"authors\":\"Merve Özkılınç Önen, Elif Everest, Turna Demirci, Pelinsu Köprülü Şen, Esra Kızıltepe Kısakesen, Yeşim Özgüler, Sinem Nihal Esatoğlu, Emire Seyahi, Eda Tahir Turanlı\",\"doi\":\"10.55563/clinexprheumatol/1sf43v\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The HLA-B51 locus has the strongest association with Behçet's syndrome (BS). The presence of a CpG island in the HLA-B gene led us to examine the role of epigenetic regulation in BS.</p><p><strong>Methods: </strong>HLA-B51 genotyping was performed via sequence-specific PCR in 15 index familial BS cases, 17 affected relatives, 26 unaffected relatives, 46 sporadic BS cases, and 41 healthy controls. HLA-B methylation level was determined using the Zymo OneStep qMethyl kit, and HLA-B51 mRNA level was assessed by quantitative real-time PCR in 14 index familial BS cases, 15 affected relatives, 15 unaffected relatives, 11 sporadic BS cases, and 10 healthy controls.</p><p><strong>Results: </strong>HLA-B51 carrier ratio was 13/15 in index familial cases, 13/17 in affected relatives, 22/26 in unaffected relatives, 8/25 in healthy controls, and 35/47 in sporadic BS cases. HLA-B51 expression level in HLA-B51+ BS cases was 2.2-fold higher than in their unaffected relatives (p=0.0149) and 1.3-fold higher than in healthy controls (p=0.0188), while sporadic BS cases had a 2.7-fold higher level than healthy controls (p=0.0487). HLA-B promoter methylation was significantly lower in HLA-B51+ familial BS cases than in unaffected relatives (0.4-fold, p=0.01), affected relatives (0.36-fold, p=0.0219), and healthy controls (0.34-fold, p=0.0371) and slightly lower in HLA-B51+ sporadic BS cases than in healthy controls (0.71-fold, p=0.2347). There was an inverse correlation between HLA-B promoter methylation and HLA-B51 expression in HLA-B51+ sporadic BS cases (p=0.0164).</p><p><strong>Conclusions: </strong>This study indicates epigenetic involvement associated with the HLA-B51 locus in BS, both in familial and sporadic cases. Further studies with larger sample sizes are needed to confirm our results.</p>\",\"PeriodicalId\":10274,\"journal\":{\"name\":\"Clinical and experimental rheumatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and experimental rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.55563/clinexprheumatol/1sf43v\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and experimental rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.55563/clinexprheumatol/1sf43v","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

研究目的HLA-B51位点与白塞氏综合征(BS)的关系最为密切。方法:通过序列特异性 PCR 对 15 例家族性白塞氏综合征病例、17 例患病亲属、26 例未患病亲属、46 例散发性白塞氏综合征病例和 41 例健康对照进行 HLA-B51 基因分型。使用 Zymo OneStep qMethyl 试剂盒测定 HLA-B 甲基化水平,并通过定量实时 PCR 评估 14 例家族性 BS 病例、15 例患病亲属、15 例未患病亲属、11 例散发性 BS 病例和 10 例健康对照的 HLA-B51 mRNA 水平:结果:HLA-B51携带者比例在家族性病例中为13/15,在患病亲属中为13/17,在未患病亲属中为22/26,在健康对照组中为8/25,在散发性BS病例中为35/47。HLA-B51+ BS病例的HLA-B51表达水平比未受影响的亲属高2.2倍(P=0.0149),比健康对照组高1.3倍(P=0.0188),而散发性BS病例的表达水平比健康对照组高2.7倍(P=0.0487)。HLA-B启动子甲基化在HLA-B51+家族性BS病例中明显低于未受影响的亲属(0.4倍,p=0.01)、受影响的亲属(0.36倍,p=0.0219)和健康对照组(0.34倍,p=0.0371),而在HLA-B51+散发性BS病例中则略低于健康对照组(0.71倍,p=0.2347)。在HLA-B51+散发性BS病例中,HLA-B启动子甲基化与HLA-B51表达呈反相关(p=0.0164):本研究表明,在家族性和散发性 BS 病例中,HLA-B51 基因座都与表观遗传学有关。要证实我们的研究结果,还需要更多样本量的进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
HLA-B gene methylation and expression in Behçet's syndrome: a potential role of epigenetics in the pathogenesis.

Objectives: The HLA-B51 locus has the strongest association with Behçet's syndrome (BS). The presence of a CpG island in the HLA-B gene led us to examine the role of epigenetic regulation in BS.

Methods: HLA-B51 genotyping was performed via sequence-specific PCR in 15 index familial BS cases, 17 affected relatives, 26 unaffected relatives, 46 sporadic BS cases, and 41 healthy controls. HLA-B methylation level was determined using the Zymo OneStep qMethyl kit, and HLA-B51 mRNA level was assessed by quantitative real-time PCR in 14 index familial BS cases, 15 affected relatives, 15 unaffected relatives, 11 sporadic BS cases, and 10 healthy controls.

Results: HLA-B51 carrier ratio was 13/15 in index familial cases, 13/17 in affected relatives, 22/26 in unaffected relatives, 8/25 in healthy controls, and 35/47 in sporadic BS cases. HLA-B51 expression level in HLA-B51+ BS cases was 2.2-fold higher than in their unaffected relatives (p=0.0149) and 1.3-fold higher than in healthy controls (p=0.0188), while sporadic BS cases had a 2.7-fold higher level than healthy controls (p=0.0487). HLA-B promoter methylation was significantly lower in HLA-B51+ familial BS cases than in unaffected relatives (0.4-fold, p=0.01), affected relatives (0.36-fold, p=0.0219), and healthy controls (0.34-fold, p=0.0371) and slightly lower in HLA-B51+ sporadic BS cases than in healthy controls (0.71-fold, p=0.2347). There was an inverse correlation between HLA-B promoter methylation and HLA-B51 expression in HLA-B51+ sporadic BS cases (p=0.0164).

Conclusions: This study indicates epigenetic involvement associated with the HLA-B51 locus in BS, both in familial and sporadic cases. Further studies with larger sample sizes are needed to confirm our results.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
6.10
自引率
18.90%
发文量
377
审稿时长
3-6 weeks
期刊介绍: Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.
期刊最新文献
Group 3 innate lymphoid cells promotes Th17 cells differentiation in rheumatoid arthritis. Mechanism of neutrophil extracellular traps in the pathogenesis of gout. Osteoarticular x-ray reading by medical students followed by eye-tracking: better understanding for better training. Understanding mechanisms of JAK1 inhibition on synovial fibroblasts using combinatorial approaches of bulk and single cell RNAseq analyses. WNT16 as a promising biomarker for systemic lupus erythematosus and its role in regulating cell proliferation and apoptosis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1