Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, 55905 Rochester, MN, USA.
Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
J Affect Disord. 2019 Feb 15;245:597-601. doi: 10.1016/j.jad.2018.11.007. Epub 2018 Nov 3.
Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder.
We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset.
P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males. Neither P2RX7 variants associated with rapid cycling among bipolar patients.
Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available.
The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects.
双相情感障碍患者在临床表现上存在性别差异，尤其是在与心境发作周期有关的亚表型方面，如快速循环。此外，最近的研究将 P2RX7 基因变异与快速循环的风险联系起来，这种风险存在于双相情感障碍患者的临床队列中，以及其他心境障碍患者中。然而，关于 P2RX7 变异与双相情感障碍之间的潜在性别差异知之甚少。
我们研究了 P2RX7（rs1621388 和 rs2230912）变异与 756 名双相情感障碍患者和 787 名年龄、性别和血统相匹配的对照患者之间的性别特异性遗传关联。我们通过比较病例和对照，以及病例中情绪发作的快速循环，检查了性别特异性与双相情感障碍的遗传关联。在独立数据集上对结果进行了复制。
P2RX7 变异暗示孔活性增加，在女性中但不在男性中更常见于双相情感障碍。P2RX7 变异与双相患者的快速循环无关。
用于 SNP 性别交互作用检验的样本量较小，限制了检验效能，并且关于快速循环发作的时间和药物使用的时间的数据不可用。
P2RX7 变异对双相情感障碍的影响可能是性别特异性的，P2X7 活性增加可能会增加女性患双相情感障碍的风险。未来研究检查 P2RX7 对双相情感障碍的影响时，应考虑性别特异性影响。
