Prevalence of Incompletely Penetrant Huntington's Disease Alleles Among Individuals With Major Depressive Disorder
Prevalence of Incompletely Penetrant Huntington's Disease Alleles Among Individuals With Major Depressive Disorder
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DOI：
10.1176/appi.ajp.2009.09070973
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发表时间：
2010-05-01
影响因子：
17.7
通讯作者：
Gusella, James
中科院分区：
文献类型：
--
作者：
Perlis, Roy H.;Smoller, Jordan W.;Gusella, James
目的：导致亨廷顿舞蹈病的亨廷顿蛋白CAG扩增突变的症状前个体可能比健康对照人群有更高水平的抑郁症状。然而，HTT CAG重复扩张在重度抑郁症患者中的患病率尚未确定。方法：对重度抑郁症个体与无重度抑郁症对照者的两个发现队列、重度抑郁症个体与无重度抑郁症对照者的重复队列进行HTT CAG等位基因大小的病例对照遗传关联研究。结果：重度抑郁症患者的3054条染色体中有6条CAG重复长度为36或更大，而对照组的4155条染色体中没有CAG重复长度。在第三个队列中，在重度抑郁症组的1202条染色体中观察到一个扩展的等位基因，而在对照组的2678条染色体中则没有。扩增重复序列的个体之间没有明确的临床特征模式。结论：在诊断为重度抑郁症的临床人群中，大约每1000人中就有3人携带扩展的HTT CAG等位基因。
Objective: Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington's disease may have higher levels of depressive symptoms than healthy comparison populations. However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established.Method: This was a case-control genetic association study of HTT CAG allele size in two discovery cohorts of individuals with major depressive disorder and comparison subjects without major depression as well as a replication cohort of individuals with major depression and comparison subjects without major depression.Results: CAG repeat lengths of 36 or greater were observed in six of 3,054 chromosomes from individuals with major depression, compared with none of 4,155 chromosomes from comparison subjects. In a third cohort, one expanded allele was observed among 1,202 chromosomes in the major depression group, compared with none of 2,678 chromosomes in comparison subjects. No clear pattern of clinical features was shared among individuals with the expanded repeats.Conclusions: In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles.