Association analysis of interleukin‐23 receptor SNPs and SAPHO syndrome in Chinese people

Abstract

Objective: SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an autoimmune disease of unknown etiology that seriously affects patients' daily lives. Family-based investigations support genetic contributions toward disease susceptibility. The present study evaluated whether the previously reported autoimmune disease-associated single nucleotide polymorphisms (SNPs) have any genetic overlap with SAPHO syndrome. Method:Genomic DNA was obtained from 71 SAPHO patients and 104 healthy controls.The SNP genotypes of each patient were determined with polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Genotype, allele, and haplotype frequencies were analyzed with SPSS software. Results: Three SNP sites (rs10889677 and rs2201841 of interleukin [IL]-23R, and rs2243248 of IL-4) showed significant correlation with the occurrence of SAPHO syndrome in additive and dominant genetic models, while rs7517847 of IL-23R showed substantial correlation with SAPHO in the dominant genetic model. The G allele of rs2243248 (IL-4) was a high risk factor for SAPHO (P = 2.41e−5, odds ratio [OR] =7.79, 95% CI: 2.59-23.3). The haplotype (A-G-C-G-T), comprising 5 SNPs of the IL-23R gene, had a significantly higher frequency in the SAPHO cohort than in the controls (P = .011, OR = 2.05, 95% CI: 1.12-3.60). Conclusion: Variants rs10889677, rs2201841, and rs7517847 of IL-23R, and variant rs2243248 of IL-4, showed strong associations with SAPHO syndrome. Patients carrying the A-G-C-G-T haplotype of IL-23 are significantly more likely to develop SAPHO syndrome. K E Y W O R D S CDKAL1, IL-23R, IL-4, SAPHO syndrome, SNPs | 2179 GUO et al.The underlying mechanisms of SAPHO syndrome are still controversial. Previous research has reported that various proteins, including Pstpip1, Pstpip2, and Lpin2, are associated with SAPHO and other autoimmune diseases. 2,3 In mice, the Laxer group found that dysregulation of IL-1 signaling can drive sterile osteomyelitis in Pstpip2-deficient mice. 4,5 However, genetic screening did not find any specific variants in the Pstpip1, Pstpip2, NOD2 or LPIN2 genes in patients with SAPHO syndrome. 6,7 Another group reported that the Mdm2 single nucleotide polymorphism (SNP) 309 G allele and the p53 SNP 72 C allele were risk alleles in a cohort of SAPHO patients. 8 In 2014, Firinu et al observed that TH17 lymphocytes were highly elevated in the peripheral blood of SAPHO subjects, suggesting that activation of the TH17 axis plays an important role in SAPHO syndrome. 9 Based on these reports, in this study we tested

The role of genetic factors and peripheral immune cells in SAPHO syndrome

“…1,2 Variants rs10889677, rs2201841, rs7517847 of IL-23R and rs2243248 of IL-4 showed strong associations with SAPHO syndrome. 3 Our results for rs7517847 of IL-23R and rs2243248 of IL-4 were similar to Guo's results. However, more studies are required to further explore our findings.…”

“…Recently, pathogenesis of DSAP was elucidated by detecting MVK, PMVK, MVD and FDPS loss-of-function mutations in patients with familiar or sporadic porokeratosis. [3][4][5][6] The mutated genes are involved in mevalonate pathway. After a second-hit mutation, it is assumed that the diminished final products of mevalonate pathway together with the accumulation of toxic metabolites result in the clinical phenotype of DSAP.…”

Role of the F-BAR Family Member PSTPIP2 in Autoinflammatory Diseases

“…Studies have shown that variants rs10889677, rs2201841, and rs7517847 of IL-23R, and variant rs2243248 of IL-4, showed strong associations with SAPHO syndrome. Patients carrying the A-G-C-G-T haplotype of IL-23 are significantly more likely to develop SAPHO syndrome ( 92 ).…”

Genome-Wide Association Identifies Risk Pathways for SAPHO Syndrome

“…Previous research reported that the dysregulation of interleukin-1 (IL-1) signaling promoted sterile osteomyelitis in Pstpip2-deficient mice (Ferguson et al, 2006;Sharma and Ferguson, 2013). However, no specific variants were found using genetic screening in the PSTPIP1, PSTPIP2, NOD2 or LPIN2 genes in SAPHO samples (Hurtado-Nedelec et al, 2010;Colina et al, 2012;Guo et al, 2019). There are several factors considered to have the role in the development of SAPHO syndrome, including Propionibacterium acnes infection (Kotilainen et al, 1996;Colina et al, 2007), impaired immune responses, over-activated TH17…”