An association analysis at 2q36 reveals a new candidate susceptibility gene for juvenile absence epilepsy and/or absence seizures associated with generalized tonic-clonic seizures

作者：Yalcin Ozlem; Baykan Betul; Agan Kadriye; Yapici Zuhal; Yalcin Destina; Dizdarer Gulsen; Turkdogan Dilsad; Ozkara Cigdem; Unalp Aycan; Uluduz Derya; Gul Gunay; Kuscu Demet; Ayta Semih; Tutkavul Kemal; Comu Sinan; Tatli Burak; Meral Cihan; Bebek Nerses; Caglayan Server Hande^*

来源：Epilepsia, 2011, 52(5): 975-983.

DOI：10.1111/j.1528-1167.2010.02970.x

• Absence epilepsy
• Association study
• Haplotype blocks
• INHA gene

Purpose: To further evaluate the previously shown linkage of absence epilepsy (AE) to 2q36, both in human and WAG/Rij absence rat models, a 160-kb region at 2q36 containing eight genes with expressions in the brain was targeted in a case-control association study involving 205 Turkish patients with AE and 219 controls.
Methods: Haplotype block and case-control association analysis was carried out using HAPLO VIEW 4.0 and inhibin alpha subunit (INHA) gene analysis by DNA sequencing.
Key Findings: An association was found between the G allele of rs7588807 located in the INHA gene and juvenile absence epilepsy (JAE) syndrome and patients having generalized tonic-clonic seizures (GTCS) with p-values of 0.003 and 0.0002, respectively (uncorrected for multiple comparisons). DNA sequence analysis of the INHA gene in 110 JAE/GTCS patients revealed three point mutations with possible damaging effects on inhibin function in three patients and the presence of a common ACTC haplotype (H1) with a possible dominant protective role conferred by the T allele of rs7588807 with respective p-values of 0.0005 and 0.0014.
Significance: The preceding findings suggest that INHA could be a novel candidate susceptibility gene involved in the pathogenesis of JAE or AE associated with GTCS.

• 出版日期2011-5