Gene Testing for Osteonecrosis of the Femoral Head in Systemic Lupus Erythematosus Using Targeted Next-Generation Sequencing: A Pilot Study

Hong-Sheng Sun 1, Qing-Rui Yang 1, Yan-Yan Bai 1, Nai-Wen Hu 1, Dong-Xia Liu 1, Cheng-Yong Qin 2

Affiliations

PMID: 32607330
PMCID: PMC7322418
DOI: 10.12998/wjcc.v8.i12.2530

Free PMC article

Abstract

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). Some gene loci such as 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 this process.

Aim: To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes.

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.

Results: Six of the 49 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).

Conclusion: The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.

Keywords: Collagen type II alpha 1 chain; Complement C3d receptor 2; Nitric oxide synthase 3; Osteonecrosis of the femoral head; Single nucleotide variations; Systemic lupus erythematosus.