Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity
Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity
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DOI：
10.1007/s12017-010-8122-x
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发表时间：
2010-06
影响因子：
3.5
通讯作者：
S. Spiczak;H. Muhle;I. Helbig;C. D. Kovel;J. Hampe;V. Gaus;B. Koeleman;D. Lindhout;S. Schreiber;T. Sander;U. Stephani
中科院分区：
文献类型：
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作者：
S. Spiczak;H. Muhle;I. Helbig;C. D. Kovel;J. Hampe;V. Gaus;B. Koeleman;D. Lindhout;S. Schreiber;T. Sander;U. Stephani
光阵发性反应（photoproxysmal response，PPR）是指大脑对光刺激的异常视觉敏感性。常与特发性全身性癫痫（IGEs）相关，可能是皮质兴奋性的内表型。瞬时受体电位阳离子（TRPC）通道参与癫痫样放电的产生，TRPC 4构成中枢神经系统中的主要TRPC通道。本研究探讨了PPR与TRPC 4基因序列变异的关系。对273例PPR先证者和599例对照者进行TRPC 4基因35个单核苷酸多态性（SNP）基因分型。针对每个SNP和相应的单倍型，对广泛的PPR内表型（PPR I-IV型;n= 273）、狭窄的受影响模型（PPR III和IV型;n= 214）以及与IGE相关的PPR（PPR/IGE;n= 106）进行了关联分析。内含子5 SNP rs 10507456与PPR/IGE在单标记水平（P= 0.005）和单倍型水平（P= 0.01）均存在相关性。同一单倍型区块内的另外三个SNP（rs 1535775、rs 10161932和rs7338118）与PPR/IGE（P < 0.05（未校正））以及位于内含子3的另外两个标记（rs 10507457、rs7329459）相关。同样，相应的单倍型也显示与PPR/IGE相关。结果没有显着的多重比较后，通过排列分析单标记和Bonferroni-Holm单倍型校正。未发现TRPC 4变异与其他表型之间存在关联。我们的结果显示TRPC 4变异与PPR/IGE有关联的趋势。进一步的研究包括更大样本的光敏先证者需要澄清TRPC 4与PPR和IGE的相关性。
Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of theTRPC4gene. Thirty-five single nucleotide polymorphisms (SNP) withinTRPC4were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV;n= 273), a narrow model of affectedness (PPR types III and IV;n= 214) and PPR associated with IGE (PPR/IGE;n= 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (P= 0.005) and haplotype level (P= 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE atP< 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni–Holm for haplotypes. No association was found between variants inTRPC4and other phenotypes. Our results showed a trend toward association ofTRPC4variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance ofTRPC4for PPR and IGE.