Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
Instituto de Parasitología y Biomedicina 'López-Neyra', CSIC, PTS Granada, Granada, Spain.
Sci Rep. 2017 Jul 11;7(1):5088. doi: 10.1038/s41598-017-03915-2.
The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46-0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.
IgA 血管炎的遗传成分仍远未阐明。为了增加对这种血管炎遗传成分的现有认识，我们对这种疾病进行了首次全基因组关联研究（GWAS）。308 名 IgA 血管炎患者和来自西班牙的 1018 名健康对照者通过 Illumina HumanCore BeadChips 进行基因分型。GWAS 数据的内插使用 1000 基因组项目第三阶段数据集作为参考面板进行。经过质量控制过滤和 GWAS 内插后，285 名患者和 1006 名对照者留在数据集中并纳入进一步分析。此外，通过内插经典等位基因和多态性氨基酸位置，全面研究了人类白细胞抗原（HLA）区域。位于 HLA Ⅱ类区域的多态性连锁不平衡块超过了全基因组的显著性水平（OR=0.56，95%CI=0.46-0.68）。尽管没有多态性氨基酸位置在全基因组水平上具有显著性关联，但在 HLA-DRB1 的位置 13 和 11 观察到潜在相关的 P 值（P=6.67E-05，P=1.88E-05）。在 HLA 之外，检测到了潜在的关联，但没有一个接近统计学意义。总之，我们的研究表明，IgA 血管炎是一种典型的 HLA Ⅱ类疾病。
