Sun HS, Yang QR, Bai YY, Hu NW, Liu DX, Qin CY. Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study. World J Clin Cases 2020; 8(12): 2530-2541 [PMID: 32607330 DOI: 10.12998/wjcc.v8.i12.2530]
Corresponding Author of This Article
Cheng-Yong Qin, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, China. qinchengyongdaoshi@163.com
Research Domain of This Article
Immunology
Article-Type of This Article
Observational Study
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Sun HS, Yang QR, Bai YY, Hu NW, Liu DX, Qin CY. Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study. World J Clin Cases 2020; 8(12): 2530-2541 [PMID: 32607330 DOI: 10.12998/wjcc.v8.i12.2530]
Hong-Sheng Sun, Qing-Rui Yang, Yan-Yan Bai, Nai-Wen Hu, Dong-Xia Liu, Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Cheng-Yong Qin, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
Author contributions: Qin CY and Yang QR designed the research; Sun HS, Bai YY, Hu NW, and Liu DX performed the research; Sun HS and Yang QR analyzed the data and wrote the paper; Sun HS and Yang QR contributed equally to this work.
Supported byNational Natural Science Foundation of China, No. 81671605.
Institutional review board statement: The study was reviewed and approved by the Shandong Provincial Hospital Affiliated to Shandong University Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. E-mail: qinchengyongdaoshi@163.com. No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Corresponding author: Cheng-Yong Qin, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, China. qinchengyongdaoshi@163.com
Received: February 24, 2020 Peer-review started: February 24, 2020 First decision: March 27, 2020 Revised: May 9, 2020 Accepted: May 19, 2020 Article in press: May 19, 2020 Published online: June 26, 2020 Processing time: 120 Days and 21.7 Hours
ARTICLE HIGHLIGHTS
Research background
Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE).
Research motivation
Complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in the onset of ONFH in SLE.
Research objectives
To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in CR2, NOS3, COL2A1, PTPN22, and TRPV4.
Research methods
SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows–wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs.
Research results
Six patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S).
Research conclusions
The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2. And the low frequency functional mutations in NOS3 had never been reported previously.
Research perspectives
These findings may have important pharmacogenetic implications. But the detailed mechanisms of the associations need to be determined in further studies.
