Ozaki N, Rosenthal N E, Pesonen U, Lappalainen J, Feldman-Naim S, Schwartz P J, Turner E H, Goldman D
Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Biol Psychiatry. 1996 Dec 15;40(12):1267-72. doi: 10.1016/0006-3223(95)00649-4.
We screened the 5-HT2A receptor gene coding region in 50 patients with seasonal affective disorder (SAD) using a single strand conformational polymorphism analysis and estimated the frequencies of two synonymous and two non-synonymous substitutions we detected in 70 Centre d'Etude du Polymorphism Humain (CEPH) population controls and 62 normal controls. Both of the amino acid substitutions: Ala447-Val447 and His452-Tyr452, were located within the cytoplasmic. C-terminal tail of the receptor. Rarer allele frequencies in CEPH were 0.7% and 9.3% for Val447 and Tyr452, respectively. Allele frequencies of all four polymorphisms, including the two amino acid substitutions, were not significantly different in SAD patients as compared to CEPH and normal controls. Lack of association of Val447 and Tyr452 to SAD is consistent with observations showing normal 5-HT2A receptor Ca2+ response in platelets with this disorder, however, the two 5-HT2A amino acid substitutions may lead to differences in behavioral phenotypes.
我们运用单链构象多态性分析方法，对50例季节性情感障碍（SAD）患者的5-HT2A受体基因编码区进行了筛查，并在70名人类多态性研究中心（CEPH）群体对照者和62名正常对照者中，估算了我们所检测到的两个同义替换和两个非同义替换的频率。这两个氨基酸替换，即丙氨酸447-缬氨酸447和组氨酸452-酪氨酸452，均位于受体的胞质C末端尾部。在CEPH中，缬氨酸447和酪氨酸452的稀有等位基因频率分别为0.7%和9.3%。与CEPH和正常对照相比，包括这两个氨基酸替换在内的所有四种多态性的等位基因频率在SAD患者中并无显著差异。缬氨酸447和酪氨酸452与SAD缺乏关联，这与该疾病患者血小板中5-HT2A受体Ca2+反应正常的观察结果一致，然而，这两个5-HT2A氨基酸替换可能会导致行为表型的差异。
