Buttenschøn Henriette N, Nielsen Marit N, Thotakura Gangadaar, Lee Chris W, Nykjær Anders, Mors Ole, Glerup Simon
aTranslational Neuropsychiatry Unit, Department of Clinical Medicine bDepartment of Biomedicine, The Lundbeck Foundation Research Center, MIND cDepartment of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University dDepartment of Psychosis, Psychosis Research Unit, Aarhus University Hospital, Risskov eThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark fDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Psychiatr Genet. 2017 Jun;27(3):89-95. doi: 10.1097/YPG.0000000000000168.
The identification of peripheral biomarkers for bipolar disorder is of great importance and has the potential to improve diagnosis, treatment and prognosis. Recent studies have reported lower plasma progranulin levels in bipolar individuals compared with controls and association with single nucleotide polymorphisms (SNPs) within the progranulin gene (GRN). In the present study, we investigated the effect of GRN and sortilin (SORT1) gene variation on serum progranulin levels in bipolar individuals and controls.
In a Danish cohort of individuals with bipolar disorder and controls, we analysed the serum progranulin level (nbipolar=80, ncontrols=76) and five SNPs located within GRN and two SNPs near the SORT1 gene encoding sortilin, a progranulin scavenger receptor known to affect circulating progranulin levels (nbipolar=166, ncontrols=186).
We observed no significant difference in the serum progranulin level between cases and controls and none of the analysed SNPs located within GRN or close to SORT1 were associated with bipolar disorder. Crude and adjusted (adjusted for case-control status, sex and age) linear regression analyses showed no effect of any SNPs on the serum progranulin level. However, we observed that the mean serum progranulin level in cases and controls is affected differently depending on the genotypes of two SNPs within GRN (rs2879096 and rs4792938).
The sample size is relatively small and detailed information on medication and polarity of the disorder is not available. No correction for multiple testing was performed.
Our study suggests that the potential of progranulin as a biomarker for bipolar disorder is genotype dependent.
鉴定双相情感障碍的外周生物标志物至关重要，且有可能改善诊断、治疗和预后。最近的研究报告称，与对照组相比，双相情感障碍患者的血浆前颗粒蛋白水平较低，且与前颗粒蛋白基因（GRN）内的单核苷酸多态性（SNP）有关。在本研究中，我们调查了GRN和sortilin（SORT1）基因变异对双相情感障碍患者和对照组血清前颗粒蛋白水平的影响。
在一个丹麦双相情感障碍患者及对照组队列中，我们分析了血清前颗粒蛋白水平（双相情感障碍患者n = 80，对照组n = 76），以及位于GRN内的5个SNP和编码sortilin（一种已知会影响循环前颗粒蛋白水平的前颗粒蛋白清除受体）的SORT1基因附近的2个SNP（双相情感障碍患者n = 166，对照组n = 186）。
我们观察到病例组和对照组之间血清前颗粒蛋白水平无显著差异，且位于GRN内或靠近SORT1的分析SNP均与双相情感障碍无关。未校正和校正（校正病例对照状态、性别和年龄）的线性回归分析显示，任何SNP对血清前颗粒蛋白水平均无影响。然而，我们观察到，根据GRN内两个SNP（rs2879096和rs4792938）的基因型不同，病例组和对照组的平均血清前颗粒蛋白水平受到的影响也不同。
样本量相对较小，且没有关于药物治疗和疾病极性的详细信息。未进行多重检验校正。
我们的研究表明，前颗粒蛋白作为双相情感障碍生物标志物的潜力取决于基因型。
