蛋白酶体调节剂 9 与 2 型糖尿病中的抑郁

Proteasome modulator 9 and depression in type 2 diabetes.

机构信息

Laboratory of Molecular Genetics of Complex & Monogenic Disorders, Department of Medicine and Cellular & Molecular Physiology, H044, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.

出版信息

Curr Med Chem. 2012;19(30):5178-80. doi: 10.2174/092986712803530593.

DOI:10.2174/092986712803530593

PMID:22934761

Abstract

BACKGROUND

The chromosome 12q24 locus is linked to bipolar disorder, depression, and type 2 diabetes (T2D). PSMD9 lies in the 12q24 locus and is linked to MODY3, T2D, T2D-nephropathy, T2D-neuropathy, retinopathy, macrovascular pathology, hypertension, and hypercholesterolemia in Italian families. Interestingly, PSMD9 gene common variants contribute to the therapeutic response to anti-depressant treatment. Further, PSMD9 is implicated in a model of prediction to susceptibility to depression.

AIMS

Our goal was to determine whether PSMD9 is linked to depression in 200 T2D Italian families.

METHODS

We characterized the Italian families' members for presence and/or absence of depression using the diagnostic criteria of DSM-IV. The phenotype was described as unknown in all cases in which the diagnosis was unclear or data were not available. We tested in the 200 Italians families for evidence of linkage of the PSMD9 single nucleotide polymorphisms (SNPs) IVS3+nt460 A > G, IVS3+nt437 T > C and E197G A > G with the depression phenotype. The non-parametric linkage analysis was performed by using the Merlin software. To rule out results due to random chance, 1000 replicates were executed.

RESULTS

The PSMD9 gene SNPs studied and/or any gene variants in linkage disequilibrium with them are linked to depression in our Italian families.

CONCLUSIONS

This is the first report of PSMD9 linkage to depression. This finding highlights the pleiotropic effects of PSMD9.

摘要

背景

染色体 12q24 位点与双相情感障碍、抑郁症和 2 型糖尿病（T2D）有关。PSMD9 位于 12q24 位点，与 MODY3、T2D、T2D-肾病、T2D-神经病、视网膜病变、大血管病变、高血压和高胆固醇血症有关在意大利家族中。有趣的是，PSMD9 基因常见变体有助于抗抑郁治疗的反应。此外，PSMD9 与预测易患抑郁症的模型有关。

目的

我们的目标是确定 PSMD9 是否与 200 个意大利 T2D 家族中的抑郁症有关。

方法

我们使用 DSM-IV 的诊断标准来描述意大利家族成员的抑郁症状况。在所有诊断不明确或数据不可用的情况下，表型被描述为未知。我们在 200 名意大利人身上测试了 PSMD9 单核苷酸多态性（SNP）IVS3+nt460 A > G、IVS3+nt437 T > C 和 E197G A > G 与抑郁表型的连锁证据。使用 Merlin 软件进行非参数连锁分析。为了排除随机机会导致的结果，执行了 1000 次重复。