Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2012;7(8):e43057. doi: 10.1371/journal.pone.0043057. Epub 2012 Aug 28.
Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatment-responsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling.
To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients.
Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients.
Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044).
P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10(-9)). The P2RX7 rs2230912 _A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls.
Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system.
快速循环是一种严重的双相情感障碍形式，其发作频率增加，对chronotherapy 和稳定的睡眠-觉醒周期特别有反应。我们假设 P2RX7 基因会受到睡眠剥夺的影响，并与快速循环有关。
评估 P2RX7 表达是否受总睡眠剥夺的影响，以及 P2RX7 的变异是否与双相情感障碍患者的快速循环有关。
对来自加利福尼亚大学欧文医学中心睡眠研究中心的健康志愿者的外周血单核细胞（PBMCs）进行基因表达分析，并对患者进行病例-病例和病例-对照 SNP/单倍型关联分析。
美国加利福尼亚大学欧文医学中心睡眠研究中心的健康志愿者（n=8）和瑞典从专门的双相情感障碍精神病诊所招募的门诊患者，诊断为双相情感障碍 1 型（快速循环：n=121）和匿名献血者对照（n=1044）。
健康志愿者的 PBMCs 在睡眠剥夺期间 P2RX7 RNA 水平显著升高（p=2.3*10(-9)）。P2RX7 rs2230912 _A 等位基因更为常见（OR=2.2，p=0.002），而 P2RX7 中的 ACGTTT 单倍型（rs1718119 到 rs1621388）包含保护性 rs2230912_G 等位基因（OR=0.45-0.49，p=0.003-0.005），在快速循环病例中比非快速循环双相情感障碍患者和献血者对照中更为少见。
睡眠剥夺增加了健康人 P2RX7 的表达，而推测活性较低的 P2RX7 rs2230912 等位基因 A 变体与双相情感障碍的快速循环有关。这支持了 P2RX7 与情感障碍有关的早期发现，并与快速循环患者的昼夜系统更为脆弱的观点一致。
