Division of Neurology, Dept of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hereditas. 2010 Dec;147(6):313-9. doi: 10.1111/j.1601-5223.2009.02115.x.
Cerebral infarction (CI) is thought to be a multifactorial disease that is affected by several environmental factors and genetic variants. N-type voltage-gated calcium channels (VGCCs), which are expressed primarily in the neurons, have various roles in neuronal functions and are especially involved with neurotransmitter release at the sympathetic nerve terminals. We considered the α1B subunit of the N-type voltage-gated calcium channel (CACNA1B) to be representative of the general characteristics of this channel type. The aim of the present study was to assess the association of the human CACNA1B gene with the occurrence of CI via a haplotype-based case-control study that used single nucleotide polymorphisms (SNPs) from the Japanese population. A total of 165 CI patients and 314 controls were enrolled in the case-controlled studies that examined three SNPs of the human CACNA1B gene (rs7042521, rs11137351, rs10780199). There were significant differences between the CI and control groups for the overall distribution of the genotypes and the presence of the recessive rs10780199. Multiple logistic regression analyses revealed that even after adjusting for confounding factors (odds ratio: 1.716), the frequencies of the A/G and G/G genotypes of rs10780199 in the CI group were significantly higher than those observed in the control group (p = 0.021). Furthermore, the C-C-G and G-G-G haplotypes of rs7042521-rs11137351-rs10780199 were significantly more frequent in the CI group than in the control group (p = 0.024 and p < 0.000). In conclusion, significant differences were noted between the CI and control patients for the specific SNPs and haplotypes in the CACNA1B gene. The results indicate that these polymorphisms and haplotypes might be genetic markers for CI.
脑梗死（CI）被认为是一种多因素疾病，受多种环境因素和遗传变异的影响。N 型电压门控钙通道（VGCCs）主要在神经元中表达，在神经元功能中具有多种作用，特别是在交感神经末梢的神经递质释放中起作用。我们认为 N 型电压门控钙通道（CACNA1B）的α1B 亚基代表了这种通道类型的一般特征。本研究旨在通过基于单核苷酸多态性（SNP）的病例对照研究评估人类 CACNA1B 基因与 CI 发生的相关性，该研究使用了日本人群的 SNP。共有 165 名 CI 患者和 314 名对照者纳入了人类 CACNA1B 基因三个 SNP（rs7042521、rs11137351、rs10780199）的病例对照研究。CI 组和对照组在基因型的总体分布和隐性 rs10780199 的存在方面存在显著差异。多因素逻辑回归分析显示，即使在调整混杂因素（比值比：1.716）后，rs10780199 的 A/G 和 G/G 基因型在 CI 组的频率仍明显高于对照组（p=0.021）。此外，rs7042521-rs11137351-rs10780199 的 C-C-G 和 G-G-G 单倍型在 CI 组中比对照组更常见（p=0.024 和 p<0.000）。综上所述，CI 组和对照组患者在 CACNA1B 基因中的特定 SNP 和单倍型存在显著差异。结果表明，这些多态性和单倍型可能是 CI 的遗传标记。
