血栓性抗磷脂综合征与 SH2B3-ATXN2 基因座表现出强烈的单倍型关联。
Thrombotic antiphospholipid syndrome shows strong haplotypic association with SH2B3-ATXN2 locus.
机构信息
Department of Genetics, Physical Anthropology and Animal Physiology. School of Science and Technology, University of the Basque Country, UPV/EHU, Leioa, Spain.
出版信息
PLoS One. 2013 Jul 3;8(7):e67897. doi: 10.1371/journal.pone.0067897. Print 2013.
BACKGROUND
Thrombotic antiphospholipid syndrome is defined as a complex form of thrombophilia that is developed by a fraction of antiphospholipid antibody (aPLA) carriers. Little is known about the genetic risk factors involved in thrombosis development among aPLA carriers.
METHODS
To identify new loci conferring susceptibility to thrombotic antiphospholipid syndrome, a two-stage genotyping strategy was performed. In stage one, 19,000 CNV loci were genotyped in 14 thrombotic aPLA+ patients and 14 healthy controls by array-CGH. In stage two, significant CNV loci were fine-mapped in a larger cohort (85 thrombotic aPLA+, 100 non-thrombotic aPLA+ and 569 healthy controls).
RESULTS
Array-CGH and fine-mapping analysis led to the identification of 12q24.12 locus as a new susceptibility locus for thrombotic APS. Within this region, a TAC risk haplotype comprising one SNP in SH2B3 gene (rs3184504) and two SNPs in ATXN2 gene (rs10774625 and rs653178) exhibited the strongest association with thrombotic antiphospholipid syndrome (p-value = 5,9 × 10(-4) OR 95% CI 1.84 (1.32-2.55)).
CONCLUSION
The presence of a TAC risk haplotype in ATXN2-SH2B3 locus may contribute to increased thrombotic risk in aPLA carriers.
背景
血栓性抗磷脂综合征是一种由抗磷脂抗体（aPLA）携带者中一部分形成的复杂形式的血栓形成倾向。关于 aPLA 携带者血栓形成发展中涉及的遗传风险因素知之甚少。
方法
为了确定新的易位赋予血栓性抗磷脂综合征易感性的易位，采用两阶段基因分型策略。在第一阶段，通过 array-CGH 在 14 例血栓性 aPLA+患者和 14 例健康对照者中对 19000 个 CNV 位进行基因分型。在第二阶段，在更大的队列（85 例血栓性 aPLA+、100 例非血栓性 aPLA+和 569 例健康对照者）中对显著的 CNV 位进行精细映射。
结果
array-CGH 和精细映射分析导致鉴定出 12q24.12 位作为血栓性 APS 的新易感性位。在该区域内，包含 SH2B3 基因中的一个 SNP（rs3184504）和 ATXN2 基因中的两个 SNP（rs10774625 和 rs653178）的 TAC 风险单倍型与血栓性抗磷脂综合征的相关性最强（p 值=5.9×10(-4)，OR 95%CI 1.84（1.32-2.55））。
结论
ATXN2-SH2B3 位的 TAC 风险单倍型的存在可能导致 aPLA 携带者的血栓形成风险增加。
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