Investigation of the tryptophan hydroxylase 2 gene in bipolar I disorder in the Romanian population
Investigation of the tryptophan hydroxylase 2 gene in bipolar I disorder in the Romanian population
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DOI：
10.1097/ypg.0b013e3283053045
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发表时间：
2008-10-01
影响因子：
0.9
通讯作者：
Cichon, Sven
中科院分区：
文献类型：
--
作者：
Grigoroiu-Serbanescu, Maria;Diaconu, Carmen C.;Cichon, Sven
目的自色氨酸羟化酶2基因（TPH 2）被发现以来，有研究报道TPH 2基因变异与双相I型（BPI）精神障碍相关。我们的第一个目标是复制最近描述的一个罕见的功能性单核苷酸多态性（SNP）（rs 17110563）和一个单倍型覆盖5'区的TPH 2与BPI在罗马尼亚人口的样本中的关联。第二个目标是调查的影响，表型性状的发病年龄，“家族史”，和“父母的起源，根据临床标准定义，TPH 2和BPI.Method之间的关联程度16 TPH 2单核苷酸多态性进行基因分型在罗马尼亚样本的198 BPI患者和180对照筛选精神疾病。结果功能性SNP rs 17110563（编码Pro206 Ser取代）存在于一名罗马尼亚BPI患者中，而在对照组中不存在。位于5 '-区域的SNPs（rs 11178997，rs 11178998，rs7954758），早先被发现与BPI在德国样本中显着相关，在单一标记水平上与整个罗马尼亚样本中的BPI无关，但在单倍型水平上提供了与父亲传播疾病的患者亚组相关的证据。进一步的证据之间的关联被确定位于TPH 2和BPI的T-区域的单倍型在整个样本中，以及在亚组的家族性病例，患者组与父亲的传输，和患者组的发病年龄低于或等于25 years.Conclusion这些数据提供了进一步的支持参与TPH 2的遗传变异在BPI的病因。Psychiatr Genet 18：240-247（C）2008 Wolters Kluwer Health vertical bar Lippincott威廉姆斯& Wilkins.
Objective Since the discovery of the tryptophan hydroxylase 2 gene (TPH2) several studies reported the association of TPH2 genetic variation with bipolar I (BPI) disorder. Our first objective was to replicate the recently described association of a rare functional single nucleotide polymorphism (SNP) (rs17110563) and of a haplotype covering the 5' region of TPH2 with BPI in a sample from the Romanian population. The second objective was to investigate the influence of the phenotypic traits 'age-of-onset', 'family history', and 'parent-of-origin, defined according to clinical criteria, on the degree of association between TPH2 and BPI.Method Sixteen TPH2 SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders. Statistical analysis of the data was performed with Haploview v.3.32 and FAMHAP.Results The functional SNP rs17110563 (encoding a Pro206Ser substitution) was present in one Romanian BPI patient and absent in controls. SNPs located in the 5'-region (rs11178997, rs11178998, rs7954758) that had earlier been found to be significantly associated with BPI in a German sample were not associated with BPI in the overall Romanian sample at the single-marker level, but gave evidence for association in a subgroup of patients with paternal transmission of the disease at the haplotypic level. Further evidence of association was identified between haplotypes located in the T-region of TPH2 and BPI in the overall sample as well as in the subgroups of familial cases, the patient group with paternal transmission, and the patient group with age of onset below or equal to 25 years.Conclusion These data provide further support for the involvement of genetic variation in TPH2 in the etiology of BPI. Psychiatr Genet 18:240-247 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.