Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene.
Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene.
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发表时间：
2005-05
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通讯作者：
C. V. van Dyck;R. Malison;L. Jacobsen;J. Seibyl;J. Staley;M. Laruelle;R. Baldwin;R. Innis;J. Gelernter
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作者：
C. V. van Dyck;R. Malison;L. Jacobsen;J. Seibyl;J. Staley;M. Laruelle;R. Baldwin;R. Innis;J. Gelernter
在编码多巴胺转运蛋白(DAT)的基因(SLC6A3)的3‘非翻译区(SLC6A3)，已发现一种涉及可变数目串联重复序列(VNTR)的多态性。这种多态有两个常见的等位基因，分别命名为10-Repeat(*10R)和9-Repeat(*9R)，它们与人类的几种临床表型有关。以前关于SLC6A3多态对DAT在较小样本中的利用度的影响的研究得出了不同的结果。方法对96例18~88岁的欧洲裔美国人进行了SLC6A3基因启动子区基因多态分析，同时进行了(123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane单光子发射计算机断层扫描(β-CIT)，以测定纹状体DAT蛋白利用率。一个特定的和不可移位的脑摄取的比率(即，V(3)‘’=[纹状体-枕骨]/枕骨)是一个与结合电位成正比的量度。本研究将9-9个纯合子和9-10个杂合子归类为SLC6A3*9R携带者，并与SLC6A3*10R纯合子对照。结果在控制年龄因素后，SLC6A3*9R携带者的纹状体DAT利用率(V(3)‘)显著高于SLC6A3*10R纯合子(F(1，93)=6.25，P=0.014，协方差分析)。与*10R纯合子(n=53，49.9+/-19.2y)相比，*9R携带者(n=41，49.8+/-19.5岁)纹状体DAT利用率平均增加8.9%。纹状体亚区分析表明，DAT基因对尾壳核和壳核均有显著影响。结论这些结果支持对欧洲裔美国人DAT水平升高与*9R等位基因相关的解释，并可能与先前观察到的DAT基因与神经精神疾病之间的关联有关。
UNLABELLED A polymorphism involving a variable number of tandem repeats (VNTR) has been described in the 3' untranslated region of the gene (SLC6A3) coding for the dopamine transporter (DAT). This polymorphism has 2 common alleles, designated as 10-repeat (*10R) and 9-repeat (*9R), that have been linked with several human clinical phenotypes. Previous investigations of the effects of the SLC6A3 polymorphism on DAT availability in smaller samples of humans have yielded divergent results. METHODS We assessed genotype at the SLC6A3 promoter VNTR polymorphism in 96 healthy European Americans (age range, 18-88 y) who also underwent SPECT with (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) for measurement of striatal DAT protein availability. A ratio of specific to nondisplaceable brain uptake (i.e., V(3)'' = [striatal -occipital]/occipital), a measure proportional to the binding potential, was derived. For this analysis, 9-9 homozygotes and 9-10 heterozygotes were grouped as SLC6A3 *9R carriers and contrasted with SLC6A3 *10R homozygotes. RESULTS The SLC6A3 *9R carriers had significantly higher striatal DAT availability (V(3)'') than did the SLC6A3 *10R homozygotes, controlling for age (F(1,93) = 6.25, P = 0.014, analysis of covariance). The *9R carriers (n = 41, 49.8 +/- 19.5 y) had a mean increase in striatal DAT availability of 8.9% relative to the *10R homozygotes (n = 53, 49.9 +/- 19.2 y). Striatal subregion analysis revealed that the effect of DAT genotype was significant for both the caudate and the putamen. CONCLUSION These results support the interpretation of higher DAT levels in association with the *9R allele in European Americans and may relate to previously observed associations between DAT genotype and neuropsychiatric diseases.