Influence of dopamine receptor gene polymorphisms on circulating T lymphocytes: A pilot study in healthy subjects
Influence of dopamine receptor gene polymorphisms on circulating T lymphocytes: A pilot study in healthy subjects
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DOI：
10.1016/j.humimm.2015.09.032
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发表时间：
2015-10-01
期刊：
影响因子：
2.7
通讯作者：
Marino, Franca
中科院分区：
文献类型：
--
作者：
Cosentino, Marco;Ferrari, Marco;Marino, Franca
多巴胺是神经免疫网络中的关键递质，通过五种多巴胺能受体（DR）起作用：D-1样D-1和D-5以及D-2样D-2、D-3和D-4。存在几种DR基因变体，并且可能影响DR表达和活性。我们评估了健康受试者外周血中的总淋巴细胞、CD 3+、CD 4+和CD 8 + T淋巴细胞及其与选定的DR基因变体（DRD 1 rs 4532和rs686、DRD 5 rs6283、DRD 2 rs 1800497和rs6277、DRD 3 rs6280和rs 1800828、DRD 4 rs747302和7 48碱基对VNTR）的关联。DRD 1 rs 4532和rs686以及DRD 5 rs6283与总淋巴细胞以及与CD 3+和CD 4+（但不与CD 8+）T淋巴细胞相关，而D-2样DR基因变异体均未显示与淋巴细胞计数相关。基于D-1样与D-2样DR活性的任意评分与总淋巴细胞、CD 3+和CD 4 + T细胞（但不与CD 8 + T细胞）相关。D-1样DR基因变异体与淋巴细胞计数之间的关联，特别是与CD 4+（而不是CD 8+）T淋巴细胞之间的关联，可能意味着在CD 4 + T细胞中D-1样DR的功能性流行率高于D-2样DR。这是第一项研究表明DR基因多态性对淋巴细胞计数，特别是对CD 4 + T细胞的影响。未来的研究应该解决DR基因变异与健康和疾病中的免疫功能之间的可能联系。这些发现与多巴胺能药物免疫效应的相关性也应仔细研究。(C)2015年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
Dopamine is a key transmitter in the neuroimmune network, acting through five dopaminergic receptors (DR): the D-1-like D-1 and D-5 and the D-2-like D-2, D-3 and D-4. Several DR gene variants exist and may affect DR expression and activity. We assessed total lymphocytes, CD3+, CD4+ and CD8+ T lymphocytes in peripheral blood of healthy subjects and their association with selected DR gene variants (DRD1 rs4532 and rs686, DRD5 rs6283, DRD2 rs1800497 and rs6277, DRD3 rs6280 and rs1800828, DRD4 rs747302 and 7 48-base pair VNTR). DRD1 rs4532 and rs686 and DRD5 rs6283 were associated with total lymphocytes, and with CD3+ and CD4+ (but not CD8+) T lymphocytes, while none of the D-2-like DR gene variants showed any association with lymphocyte counts. An arbitrary score based on the activity of D-1-like vs D-2-like DR correlated with total lymphocytes, CD3+ and CD4+ T cells (but not with CD8+ T cells). The association between D-1-like DR gene variants and lymphocyte count, and in particular with CD4+ (but not CD8+) T lymphocytes, may imply a functional prevalence of D-1-like over D-2-like DR in CD4+ T cells. This is the first study showing an influence of DR gene polymorphisms on lymphocyte count, and in particular on CD4+ T cells. Future studies should address the possible association between DR gene variants and the immune function in health and disease. The relevance of these findings for the immune effects of dopaminergic agents should be also carefully examined. (C) 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.