Abou Jamra Rami, Gobina Carl Motinda, Becker Tim, Georgi Alexander, Schulze Thomas G, Schmael Christine, Cichon Sven, Propping Peter, Rietschel Marcella, Nöthen Markus M, Schumacher Johannes
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Psychiatr Genet. 2008 Aug;18(4):199-203. doi: 10.1097/YPG.0b013e3283050a83.
Vesicle-associated membrane proteins 2 and 3 (VAMP2 and VAMP3) are required for the release of D-serine, a competitive agonist of the neurotransmitter glycine at the glutamatergic N-methyl-D-aspartate receptors. Several lines of evidence point to an involvement of altered D-serine levels in the central nervous system in the aetiology of bipolar affective disorder (BPAD). Strong association findings between BPAD and two genes, G72 and DAAO, which are involved in the enzymatic degradation of D-serine, are reported. Based on the functional evidence and on the hypothesis that further genes, which are involved in the regulation of D-serine, could be involved in the disease aetiology, we considered VAMP2 and VAMP3 as candidate genes for BPAD.
We analyzed three and four single nucleotide polymorphism (SNP) markers covering VAMP2 and VAMP3, respectively, in an initial BPAD case-control sample of German descent (409 cases, 407 controls). For replication, we analyzed three SNP markers covering VAMP2 in a second sample of the same ethnicity (378 cases, 384 controls).
Although no association was found for VAMP3 markers, we observed evidence of association with SNPs at the VAMP2 locus in the initial sample (P values between 0.005 and 0.033). To validate these findings, we analyzed a second BPAD sample and failed to replicate the initial findings at the single-marker and haplotypic level.
In conclusion, our results do not suggest that a common genetic variant at VAMP2 or VAMP3 contributes to the development of BPAD in German patients.
囊泡相关膜蛋白2和3（VAMP2和VAMP3）是D-丝氨酸释放所必需的，D-丝氨酸是谷氨酸能N-甲基-D-天冬氨酸受体处神经递质甘氨酸的竞争性激动剂。多条证据表明，中枢神经系统中D-丝氨酸水平的改变与双相情感障碍（BPAD）的病因有关。据报道，BPAD与参与D-丝氨酸酶促降解的两个基因G72和DAAO之间存在强关联。基于功能证据以及进一步参与D-丝氨酸调节的基因可能参与疾病病因的假设，我们将VAMP2和VAMP3视为BPAD的候选基因。
在一个德裔的初始BPAD病例对照样本（409例病例，407例对照）中，我们分别分析了覆盖VAMP2和VAMP3的3个和4个单核苷酸多态性（SNP）标记。为了进行重复验证，我们在相同种族的第二个样本（378例病例，384例对照）中分析了覆盖VAMP2的3个SNP标记。
虽然未发现VAMP3标记存在关联，但我们在初始样本中观察到与VAMP2基因座的SNP存在关联的证据（P值在0.005至0.033之间）。为了验证这些发现，我们分析了第二个BPAD样本，但未能在单标记和单倍型水平上重复初始发现。
总之，我们的结果并不表明VAMP2或VAMP3的常见基因变异会导致德国患者患BPAD。
