Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
J Affect Disord. 2013 Sep 5;150(2):261-5. doi: 10.1016/j.jad.2013.04.004. Epub 2013 May 13.
A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese.
We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients.
The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06-1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects.
The relative small sample size in BD group should be considered a limitation of this study.
Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.
越来越多的证据表明，重度抑郁症（MDD）和双相情感障碍（BD）存在共同的遗传易感性，这表明这两种疾病之间存在一定的遗传重叠。全基因组关联研究已经确定了 L 型电压门控钙通道基因（CACNA1C）α-1 C 亚基的单核苷酸多态性与 MDD 和 BD 的一致关联，表明 CACNA1C 是一种有前途的易感性候选基因。在本研究中，我们检测了 CACNA1C 与汉族人 MDD 和 BD 的关联。
我们对 635 名 MDD 患者、286 名 BD 患者和 730 名正常对照患者进行了三个潜在功能多态性的基因分型。
SNP rs1051375 的基因型频率在 BD 组和对照组之间存在统计学差异（P=0.005）。在等位基因水平上，BD 患者和对照组之间 rs1051375 的 G 等位基因频率差异也具有显著性（P=0.011；OR=1.30，95%CI：1.06-1.58）。我们发现，rs1051375 携带者 GG 基因型的发病年龄比 AG 或 AA 基因型的发病年龄低，GG、AG 和 AA 携带者的平均发病年龄分别为 24.04±4.22、25.76±4.75 和 25.78±4.33 岁。三个多态性的基因型和等位基因频率在 MDD 患者和对照组之间均无显著差异。
BD 组的相对较小样本量应被视为本研究的一个局限性。
我们的初步发现支持 CACNA1C 作为 BD 易感性的遗传风险因素的潜在关联。
