Inserm U, Paris, France.
Orphanet J Rare Dis. 2011 Jul 29;6:52. doi: 10.1186/1750-1172-6-52.
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but extremely severe cutaneous adverse drug reactions in which drug-specific associations with HLA-B alleles were described.
To investigate genetic association at a genome-wide level on a large sample of SJS/TEN patients.
We performed a genome wide association study on a sample of 424 European cases and 1,881 controls selected from a Reference Control Panel.
Six SNPs located in the HLA region showed significant evidence for association (OR range: 1.53-1.74). The haplotype formed by their risk allele was more associated with the disease than any of the single SNPs and was even much stronger in patients exposed to allopurinol (OR(allopurinol) = 7.77, 95%CI = [4.66; 12.98]). The associated haplotype is in linkage disequilibrium with the HLA-B*5801 allele known to be associated with allopurinol induced SJS/TEN in Asian populations.
The involvement of genetic variants located in the HLA region in SJS/TEN is confirmed in European samples, but no other locus reaches genome-wide statistical significance in this sample that is also the largest one collected so far. If some loci outside HLA play a role in SJS/TEN, their effect is thus likely to be very small.
史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）是罕见但极其严重的药物不良反应，其中描述了药物与 HLA-B 等位基因的特异性关联。
在大型 SJS/TEN 患者样本中进行全基因组水平的遗传关联研究。
我们对来自参考对照面板的 424 例欧洲病例和 1881 例对照进行了全基因组关联研究。
位于 HLA 区域的 6 个 SNP 显示出与疾病显著相关的证据（OR 范围：1.53-1.74）。由其风险等位基因形成的单倍型与疾病的相关性强于任何单个 SNP，并且在暴露于别嘌醇的患者中更为显著（OR(allopurinol) = 7.77, 95%CI = [4.66; 12.98]）。相关单倍型与 HLA-B*5801 等位基因呈连锁不平衡，已知该等位基因与亚洲人群中的别嘌醇诱导的 SJS/TEN 相关。
位于 HLA 区域的遗传变异在欧洲样本中证实了 SJS/TEN 的参与，但在该样本中，没有其他基因座达到全基因组统计学意义，该样本也是迄今为止收集到的最大样本。如果 HLA 以外的某些基因座在 SJS/TEN 中起作用，那么它们的作用可能非常小。
