Kunugi H, Hattori M, Kato T, Tatsumi M, Sakai T, Sasaki T, Hirose T, Nanko S
Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan.
Mol Psychiatry. 1997 Oct-Nov;2(6):457-62. doi: 10.1038/sj.mp.4000334.
There is some evidence suggesting that a polymorphism of variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter (5-HTT) gene and another variation which lies 1.2 kb upstream of the promoter of the gene (5-HTTLPR) are associated with affective disorders. However, conflicting results have also been reported. We examined an allelic association of these two polymorphisms in a Japanese sample of 191 patients with affective disorders (142 bipolar and 49 unipolar) and 212 controls. Substantial differences in the number and frequency of alleles between Caucasians and Japanese were observed for both polymorphisms. A significant association between the VNTR polymorphism and bipolar disorder (genotypic association: odds ratio 2.2, 95% CI 1.2-4.0; allelic association: odds ratio 1.7, 95% CI 1.0-3.0) was found, but not between the 5-HTTLPR polymorphism and bipolar disorder. No significant association with unipolar depression was detected using either genetic marker, although this may be attributable to the relatively small number of subjects with unipolar depression. Our results suggest that the VNTR itself or another unknown functional polymorphism which would be in linkage disequilibrium to the VNTR has an effect on susceptibility to bipolar disorder.
有证据表明，血清素转运体（5-HTT）基因第二内含子中的可变串联重复序列（VNTR）多态性以及该基因启动子上游1.2 kb处的另一种变异（5-HTTLPR）与情感障碍有关。然而，也有相互矛盾的报道。我们在191名情感障碍患者（142例双相情感障碍和49例单相情感障碍）和212名对照的日本样本中研究了这两种多态性的等位基因关联。在白种人和日本人之间，两种多态性的等位基因数量和频率均存在显著差异。发现VNTR多态性与双相情感障碍之间存在显著关联（基因型关联：优势比2.2，95%可信区间1.2 - 4.0；等位基因关联：优势比1.7，95%可信区间1.0 - 3.0），但5-HTTLPR多态性与双相情感障碍之间无显著关联。使用任一遗传标记均未检测到与单相抑郁症的显著关联，尽管这可能归因于单相抑郁症患者数量相对较少。我们的结果表明，VNTR本身或与VNTR处于连锁不平衡的另一种未知功能多态性对双相情感障碍的易感性有影响。
