Greenberg D A, Durner M, Shinnar S, Resor S, Rosenbaum D, Klotz I, Dicker E, Keddache M, Zhou G, Yang X, Altstiel L
Department of Psychiatry, Mount Sinai Medical Center, New York, NY 10029, USA.
Neurology. 1996 Sep;47(3):750-5. doi: 10.1212/wnl.47.3.750.
Reports have suggested an association of juvenile myoclonic epilepsy (JME) with an HLA-DR allele. We examined the HLA-DR and DQ frequencies in two populations of epilepsy patients: (1) JME patients and (2) patients with other forms of adolescent-onset, idiopathic generalized epilepsy (IGE). We did DNA-based HLA typing on 24 JME patients and 24 patients with non-JME forms of adolescent-onset IGE, forms that are clinically similar to JME. In typing the HLA region, we paid particular attention to the alleles contributing to the HLA-DR13 type and also to the DQB1 locus alleles that are in linkage disequilibrium with the alleles that comprise the DR13 type. We also examined the HLA-AP locus, which is centromeric to the DR locus. The frequency of DR13 was significantly higher in JME compared with the non-JME patients. Nine JME patients, compared with two non-JME patients, carried that type (chi 2 = 5.78 [p < 0.017, 1 df]). The odds ratio was 6.6. Furthermore, the DQB1 alleles in linkage disequilibrium with the alleles contributing to the DR13 type were also more frequent in JME than in non-JME epilepsy patients. The chi 2 is highly significant (8.1, p < 0.005) with an odds ratio of 13.8. These results confirm that JME is an HLA-associated form of epilepsy. They also show that the JME locus probably lies within the HLA region, most likely between the HLA-DP and HLA-B loci. The association studies also confirm linkage results showing that JME is genetically different from some other IGEs and emphasize that careful diagnosis is critical to genetic studies of the epilepsies.
有报告指出青少年肌阵挛性癫痫（JME）与一种HLA - DR等位基因有关联。我们检测了两组癫痫患者群体中的HLA - DR和DQ频率：（1）JME患者；（2）其他形式的青少年起病的特发性全身性癫痫（IGE）患者。我们对24例JME患者和24例非JME形式的青少年起病的IGE患者进行了基于DNA的HLA分型，这些非JME形式在临床上与JME相似。在对HLA区域进行分型时，我们特别关注了构成HLA - DR13型的等位基因以及与构成DR13型的等位基因处于连锁不平衡状态的DQB1位点等位基因。我们还检测了位于DR位点着丝粒侧的HLA - AP位点。与非JME患者相比，JME患者中DR13的频率显著更高。9例JME患者携带该类型，而只有2例非JME患者携带（χ2 = 5.78 [p < 0.017，1自由度]）。优势比为6.6。此外，与构成DR13型的等位基因处于连锁不平衡状态的DQB1等位基因在JME患者中也比在非JME癫痫患者中更常见。χ2值非常显著（8.1，p < 0.005），优势比为13.8。这些结果证实JME是一种与HLA相关的癫痫类型。它们还表明JME基因座可能位于HLA区域内，最有可能在HLA - DP和HLA - B基因座之间。关联研究也证实了连锁结果，表明JME在遗传上与其他一些IGE不同，并强调仔细诊断对癫痫的遗传学研究至关重要。
