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首页> 外文期刊>Arthritis & Rheumatism >Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus
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Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus

机译：在新生儿狼疮心脏表现的全基因组关联研究中鉴定6p21和21q22的候选基因座

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ObjectiveCardiac manifestations of neonatal lupus, comprising atrioventricular conduction defects and cardiomyopathy, occur in fetuses exposed to anti-Ro/SSA antibodies, and carry substantial mortality. There is strong evidence of a genetic contribution to the risk. This study was undertaken to evaluate single-nucleotide polymorphisms (SNPs) for associations with cardiac neonatal lupus.MethodsChildren of European ancestry with cardiac neonatal lupus (n = 116) were genotyped using the Illumina 370K SNP platform and merged with 3,351 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for association with cardiac neonatal lupus were determined.ResultsThe 17 most significant associations with cardiac neonatal lupus were found in the HLA region. The region near the MICB gene showed the strongest variant (rs3099844; Pdom = 4.52 × 10−10, OR 3.34 [95% CI 2.29–4.89]), followed by a missense variant within C6orf10 (rs7775397; Pdom = 1.35 × 10−9, OR 3.30), which lies between NOTCH4 and BTNL2, and several SNPs near the tumor necrosis factor gene, including rs2857595 (Padd = 1.96 × 10−9, OR 2.37), rs2230365 (Padd = 1.00 × 10−3, OR 0.46), and rs3128982 (Padd = 6.40 × 10−6, OR 1.86). Outside the HLA region, an association was detected at 21q22, upstream of the transcription regulator ets-related isoform 1 (rs743446; P = 5.45 × 10−6, OR 2.40). HLA notwithstanding, no individual locus previously implicated in autoimmune diseases achieved genome-wide significance.ConclusionThese results suggest that variation near genes related to inflammatory and apoptotic responses may promote cardiac injury initiated by passively acquired autoantibodies.
机译：目的新生儿的狼疮的心脏表现，包括房室传导缺陷和心肌病，发生在暴露于抗Ro / SSA抗体的胎儿中，并导致大量死亡。有强有力的证据表明遗传因素会导致这种风险。这项研究旨在评估单核苷酸多态性（SNP）与心脏新生儿狼疮的相关性。方法使用Illumina 370K SNP平台对欧洲血统新生儿心脏狼疮的儿童（n = 116）进行基因分型，并与3,351个对照合并。确定与心脏新生儿狼疮相关的几率（OR）和95％置信区间（95％CI）。结果在HLA地区发现了与心脏新生儿狼疮相关的17个最显着的关联。 MICB基因附近的区域显示出最强的变异（rs3099844； P dom = 4.52×10 −10 ，OR 3.34 [95％CI 2.29–4.89]），其次是C6orf10中的一个错义变体（rs7775397; P dom = 1.35×10 −9 或3.30），位于NOTCH4和BTNL2之间，并且在肿瘤坏死因子附近有多个SNP基因，包括rs2857595（P add = 1.96×10 −9 ，或2.37），rs2230365（P add = 1.00×10 −3 ，或0.46）和rs3128982（P add = 6.40×10 -6 ，或1.86）。在HLA区域外，在转录调节子相关的亚型1的上游21q22处检测到关联（rs743446； P = 5.45×10 -6 ，或2.40）。尽管存在HLA，但以前没有涉及自身免疫疾病的基因座在全基因组中具有重要意义。结论这些结果表明，与炎症和凋亡反应相关的基因附近变异可能会促进被动获得性自身抗体引发的心脏损伤。

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