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J Autoimmunity:白塞病的性别特异性分析揭示男性患者的遗传风险更高

2022-08-21 MedSci原创 MedSci原创

与女性患者相比,患有白塞病的男性患者具有更高的遗传风险。这种遗传差异主要来自土耳其队列,主要由HLA区域内的风险解释。这些数据表明,遗传因素可能导致男性和女性白塞病患者的疾病表现存在差异。

目标:白塞氏病在男性中往往比女性更严重。本研究旨在调查白塞病的性别特异性遗传效应。

方法:共研究了来自六个不同人群的1762名男性和1216名女性白塞病患者,其中大多数患者来自土耳其。使用Infinium ImmunoArray-24 BeadChip进行基因分型,或从可用的基因分型数据中提取。在估算和广泛的质量控制措施之后,对土耳其队列中的男性和女性患者进行了全基因组关联分析,然后对所有六个人群的显著结果进行了荟萃分析。此外,计算并比较了男性和女性患者白塞病的加权遗传风险评分。

结果:比较土耳其白塞病男性和女性患者的遗传关联分析显示,HLA区域内HLA-B/MICA 中的男性与GWAS显著性水平相关(rs2848712OR=1.46P = 1.22×10-8)。对六个人群中rs2848712 影响的荟萃分析证实了这些结果。与来自土耳其的女性患者相比,男性白塞病的遗传风险评分显著高于女性。在男性患者中观察到白塞病的遗传风险较高,HLA-B/MICA (rs116799036, OR=1.45, P=1.95×10-8)HLA-C (rs12525170, OR=1.46, P=5.66×10-7) ) KLRC4 (rs2617170, OR=1.20, P=0.019)。相比之下,IFNGR1rs4896243OR = 0.86P = 0.011)被证明在女性患者中具有更高的遗传风险。

结论:与女性患者相比,患有白塞病的男性患者具有更高的遗传风险。这种遗传差异主要来自土耳其队列,主要由HLA区域内的风险解释。这些数据表明,遗传因素可能导致男性和女性白塞病患者的疾病表现存在差异。

原始出处:

Yun Gun Jo, Lourdes Ortiz Fernández, Patrick Coit, et al. Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients, Journal of Autoimmunity, Volume 132, 2022,102882, ISSN 0896-8411, https://doi.org/10.1016/j.jaut.2022.102882.

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