Guo Changlong, Li Chen, Han Feifei, Gao Jianen, Ma Xu
National Research Institute for Family Planning, Beijing, China.
Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Int J Rheum Dis. 2019 Dec;22(12):2178-2184. doi: 10.1111/1756-185X.13741. Epub 2019 Nov 8.
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.
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.
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).
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.
滑膜炎、痤疮、脓疱病、骨肥厚和骨炎综合征（SAPHO综合征）是一种病因不明的自身免疫性疾病，严重影响患者的日常生活。基于家系的研究支持遗传因素对疾病易感性的影响。本研究评估先前报道的自身免疫性疾病相关单核苷酸多态性（SNP）与SAPHO综合征是否存在遗传重叠。
从71例SAPHO患者和104例健康对照中获取基因组DNA。采用聚合酶链反应和基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）测定每位患者的SNP基因型。使用SPSS软件分析基因型、等位基因和单倍型频率。
三个SNP位点（白细胞介素[IL]-23R的rs10889677和rs2201841，以及IL-4的rs2243248）在加性和显性遗传模型中与SAPHO综合征的发生显著相关，而IL-23R的rs7517847在显性遗传模型中与SAPHO显著相关。rs2243248（IL-4）的G等位基因是SAPHO的高风险因素（P = 2.41e-5，比值比[OR]=7.79，95%可信区间：2.59 - 23.3）。包含IL-23R基因5个SNP的单倍型（A-G-C-G-T）在SAPHO队列中的频率显著高于对照组（P = 0.011，OR = 2.05，95%可信区间：1.12 - 3.60）。
IL-23R的rs10889677、rs2201841和rs7517847变异，以及IL-4的rs2243248变异与SAPHO综合征密切相关。携带IL-23 A-G-C-G-T单倍型的患者患SAPHO综合征的可能性显著更高。
