| 程晓菲,杨倩,聂旖柔,张蒙蒙,谢怡,李名立.CACNA1G基因rs757415多态性对双相障碍患者脑灰质体积的影响[J].四川精神卫生杂志,2024,37(5):396-402.Cheng Xiaofei,Yang Qian,Nie Yirou,Zhang Mengmeng,Xie Yi,Li Mingli,Impact of the CACNA1G rs757415 polymorphism on grey matter volume in patients with bipolar disorder[J].SICHUAN MENTAL HEALTH,2024,37(5):396-402 |
| CACNA1G基因rs757415多态性对双相障碍患者脑灰质体积的影响 |
| Impact of the CACNA1G rs757415 polymorphism on grey matter volume in patients with bipolar disorder |
| 投稿时间：2024-02-04 |
| DOI：10.11886/scjsws20240204001 |
| 中文关键词: 双相障碍 CACNA1G基因 单核苷酸多态性 灰质体积 等位基因 |
| 英文关键词:Bipolar disorder CACNA1G Single nucleotide polymorphism Gray matter volume Allele |
| 基金项目:国家自然科学基金（项目名称：电压门控钙离子通道基因影响双相情感障碍神经环路的分子遗传机制研究，项目编号：82071524） |
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| 中文摘要: |
| 背景 双相障碍是一组以（轻）躁狂和抑郁反复发作为特征的严重精神障碍，其病理机制尚不明确。研究显示，电压门控钙离子通道基因可能通过影响大脑结构参与双相障碍的发生。目的 比较双相障碍患者与健康对照者之间脑灰质体积（GMV）的差异，探索电压门控钙离子通道α1亚基G（CACNA1G）基因rs757415多态性对双相障碍患者脑GMV的影响，寻找与双相障碍遗传风险相关的脑区，为进一步明确双相障碍的发病机制提供参考。方法 纳入2013年9月—2022年12月于四川大学华西医院心理卫生中心治疗的、符合《精神障碍诊断与统计手册（第4版）》（DSM-IV）双相障碍诊断标准的289例患者为患者组，同期于四川大学及附近社区招募322名健康志愿者为对照组。使用3.0 T磁共振扫描仪对受试者进行全脑扫描获取GMV数据，通过imLDRTM法检测CACNA1G基因rs757415多态性。采用Spearman相关分析考查双相障碍患者异常脑区与临床特征之间的相关性；采用full factor法分析CACNA1G基因rs757415多态性与诊断对脑GMV的交互作用。结果 最终共173例患者和207名对照组完成本研究。与对照组相比，患者组左侧小脑山坡延伸至小脑前叶、后叶、海马旁回及枕下回（t=5.664，P<0.05），右侧小脑前叶、后叶、梭状回、海马旁回及舌回（t=4.583，P<0.05），双侧前扣带回、旁扣带回、额上回及楔前叶（t=7.543，P<0.05），左侧舌回延伸至颞上回（t=6.593，P<0.05），右侧岛叶延伸至中央盖（t=7.153，P<0.05）的GMV更小。相关分析结果显示，双相障碍患者的病程与脑脊液体积呈正相关（r=0.258，P=0.003），与左侧小脑山坡延伸至小脑前叶、后叶、枕下回及海马旁回（r=-0.204，P=0.019），右侧小脑前叶延伸至小脑后叶、梭状回、海马旁回及舌回（r=-0.238，P=0.006），双侧额上回延伸至前扣带回、旁扣带回、楔前叶（r=-0.219，P=0.012），左侧舌回延伸至颞上回（r=-0.296，P=0.001），右侧岛叶延伸至中央盖（r=-0.257，P=0.003）的GMV均呈负相关。右侧海马旁回、梭状回和小脑-4-5区的GMV存在CACNA1G基因rs757415多态性与诊断的交互效应（F=19.967，P<0.05）。在对照组中，非风险等位基因携带者右侧海马旁回、梭状回、小脑-4-5区的GMV较风险等位基因携带者更大；在患者组中，风险等位基因携带者右侧海马旁回、梭状回、小脑-4-5区的GMV较非风险等位基因携带者更大；携带风险等位基因的双相障碍患者右侧海马旁回、梭状回、小脑-4-5区的GMV较对照者更大。结论 CACNA1G基因rs757415多态性可能影响双相障碍患者右侧海马旁回、梭状回和小脑-4-5区的GMV。 |
| 英文摘要: |
| Background Bipolar disorder is a severe mental disorder characterized by cycling between mania/hypomania and depression， yet its underlying pathophysiological mechanism remains unclear. Several prior studies have suggested a potential role for voltage-gated calcium channel subunit genes in the etiology of bipolar disorder， particularly in their influence on brain structure.Objective To investigate the differences in grey matter volume （GMV） for individuals with bipolar disorder compared to healthy controls， and to explore the potential influence of calcium channel voltage-dependent T-type α1 G subunit （CACNA1G） rs757415 polymorphism on GMV in bipolar disorder and clarify the specific brain regions associated with this genetic variation， thus offering a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder.Methods A cohort of 289 patients who met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） criteria for bipolar disorder were selected for participation. These patients were either admitted to hospital or examined in outpatient clinic for bipolar disorder at the Mental Health Center of West China Hospital， Sichuan University between September 2013 and December 2022. Another 322 healthy individuals were concurrently recruited as a control group from Sichuan University and surrounding communities. All participants underwent brain imaging using a 3.0 T magnetic resonance scanner to acquire data on GMV. Additionally， the presence of the CACNA1G rs757415 polymorphism was validated using the imLDRTM technique. Spearman correlation analysis was utilized to investigate potential relationship between abnormal brain regions identified through GMV data and clinical characteristics of the patients. Then the genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed using the full factor method.Results The study successfully enrolled 173 patients with bipolar disorder and 207 healthy controls who completed all the necessary procedures. Analyses revealed decreased GMV for patients with bipolar disorder compared to healthy controls in the left cerebellar declive extending to cerebellar anterior/posterior lobe， fusiform gyrus， parahippocampal gyrus and inferior occipital gyrus （t=5.664， P<0.05）； in the right cerebellar anterior/posterior lobe， fusiform gyrus， parahippocampal gyrus extending to lingual gyrus （t=4.583， P<0.05）； in the bilateral anterior cingulate/paracingulate gyri， superior frontal gyrus and precuneus （t=7.543， P<0.05）； in the left lingual gyrus and superior temporal gyrus （t=6.593， P<0.05）； and in the right insula entending to central operculum （t=7.153， P<0.05）. Correlation analysis indicated that the duration of bipolar disorder was positively correlated with cerebrospinal fluid volume （r=0.258， P=0.003）， whereas negatively correlated with the GMV in the left cerebellar declive extending to cerebellar anterior/posterior lobe， inferior occipital gyrus and parahippocampal gyrus （r=-0.204， P=0.019）， in the right cerebellar anterior lobe extending to right cerebellar posterior lobe， fusiform gyrus， parahippocampal gyrus and lingual gyrus （r=-0.238， P=0.006）， in the bilateral superior frontal gyrus extending to anterior cingulate/paracingulate gyri and precuneus （r=-0.219， P=0.012）， in the left lingual gyrus extending to superior temporal gyrus （r=-0.296， P=0.001）， and in the right insula extending to central operculum （r=-0.257， P=0.003）. A significant genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed in the right parahippocampal gyrus - fusiform gyrus - cerebellum 4-5 （F=19.967， P<0.05） . In the control group， individuals carrying the non-risk allele showed increased GMV in the right parahippocampal gyrus - fusiform gyrus - cerebellum 4-5 compared to those carrying the risk allele. In contrast， within the patient group， risk allele carriers exhibited increased GMV in the same brain regions when compared to non-risk allele carriers. Moreover， the GMV in the right parahippocampal gyrus - fusiform gyrus - cerebellum 4-5 of patients with bipolar disorder carrying risk alleles was increased compared to healthy controls.Conclusion CACNA1G rs757415 polymorphism may affect the GMV in the right parahippocampal gyrus， fusiform gyrus and cerebellum 4/5 of patients with bipolar disorder. ［Funded by National Natural Science Fundation of China， （number， 82071524）］ |
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