性别特异性分析显示男性白塞病患者存在更高的遗传风险。
Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients.
机构信息
Division of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
出版信息
J Autoimmun. 2022 Oct;132:102882. doi: 10.1016/j.jaut.2022.102882. Epub 2022 Aug 18.
OBJECTIVES
Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease.
METHODS
A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients.
RESULTS
Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients.
CONCLUSIONS
Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.
目的
贝切特病在男性中比女性更严重。本研究旨在探讨贝切特病的性别特异性遗传效应。
方法
共纳入来自 6 个不同人群的 1762 名男性和 1216 名女性贝切特病患者，其中大多数患者为土耳其裔。采用 Infinium ImmunoArray-24 BeadChip 进行基因分型，或从现有基因分型数据中提取。经过嵌合和广泛的质量控制措施后，在土耳其队列中比较男性和女性患者进行全基因组关联分析，然后对所有 6 个人群的显著结果进行荟萃分析。此外，计算了贝切特病的加权遗传风险评分，并比较了男性和女性患者之间的评分。
结果
比较来自土耳其的贝切特病男性和女性患者的遗传关联分析显示，HLA 区域内 HLA-B/MICA 与男性性别相关，具有全基因组关联分析水平的显著性（rs2848712，OR=1.46，P=1.22×10）。在六个人群中对 rs2848712 的效应进行荟萃分析证实了这些结果。来自土耳其的男性和女性患者中，贝切特病的遗传风险评分在男性中明显高于女性。在 HLA-B/MICA（rs116799036，OR=1.45，P=1.95×10）、HLA-C（rs12525170，OR=1.46，P=5.66×10）和 KLRC4（rs2617170，OR=1.20，P=0.019）中，男性患者的贝切特病遗传风险更高。相比之下，IFNGR1（rs4896243，OR=0.86，P=0.011）在女性患者中表现出更高的遗传风险。
结论
与女性患者相比，男性贝切特病患者具有更高的遗传风险。这种遗传差异主要来自我们的土耳其队列，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贝切特病患者在疾病表现上存在差异。
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