Geller Barbara, Tillman Rebecca, Badner Judith A, Cook Edwin H
Washington University School of Medicine, St. Louis, MO 63110, USA.
Bipolar Disord. 2005 Dec;7(6):610-6. doi: 10.1111/j.1399-5618.2005.00259.x.
To examine family-based transmission of the number of 5' flanking arginine vasopressin V1a receptor (AVPR1A) microsatellites, which include [(GATA)(14)] and complex [(CT)(4)-TT-(CT)(8)-(GT)(24)] repeats, in probands with a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP). Preferential transmission of the number of AVPR1A microsatellite repeats to hypersexual and uninhibited people-seeking probands was hypothesized, based on reports from preclinical work in the literature.
Probands were 83 participants in an ongoing controlled study of PEA-BP. The PEA-BP phenotype was defined by DSM-IV mania with at least one of the cardinal symptoms of mania (elation and/or grandiosity) to avoid diagnosing mania only by symptoms that overlapped with those for attention-deficit hyperactivity disorder (ADHD). Comprehensive assessment of the probands included separate Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) interviews of parents about their children and of children about themselves. Hypersexuality and uninhibited people-seeking were assessed from the corresponding WASH-U-KSADS items. Microsatellite genotyping of the AVPR1A repeats was conducted using fluorescently labeled primers and detected by laser-induced fluorescence. Alleles were determined with the assistance of semi-automated allele-calling software. There were 32 complete, biological trios (28 informative families) for the GATA repeat and 34 complete, biological trios (30 informative families) for the complex repeat. Data were analyzed using case-control and family-based association methods.
Preferential transmission of AVPR1A GATA or complex repeats was not significant for hypersexuality or uninhibited people-seeking, using the transmission disequilibrium test. Similarly, case-control analyses found no significant associations between hypersexuality or uninhibited people-seeking and the number of AVPR1A GATA or complex repeats. For p < 0.05, there was about 80% power to detect odds ratios of 5.0 and 4.0 (in the family-based analyses) and 3.5 and 2.6 (in the case-control analyses), for allele frequencies of 0.1 and 0.5, respectively.
Preferential transmission of AVPR1A to hypersexual or uninhibited people-seeking probands was not supported.
研究5'侧翼精氨酸加压素V1a受体（AVPR1A）微卫星数量的家族性传递情况，这些微卫星包括[(GATA)(14)]以及复合[(CT)(4)-TT-(CT)(8)-(GT)(24)]重复序列，研究对象为具有青春期前及青春期早期双相情感障碍表型（PEA-BP）的先证者。基于文献中的临床前研究报告，推测AVPR1A微卫星重复序列数量会优先传递给性欲亢进和无节制寻求他人的先证者。
先证者为83名正在进行的PEA-BP对照研究的参与者。PEA-BP表型由DSM-IV躁狂症定义，伴有至少一种躁狂症的主要症状（欣快和/或夸大），以避免仅通过与注意力缺陷多动障碍（ADHD）重叠的症状来诊断躁狂症。对先证者的综合评估包括圣路易斯华盛顿大学分别针对父母关于其子女以及子女关于自身的情感障碍和精神分裂症儿童量表（WASH-U-KSADS）访谈。从相应的WASH-U-KSADS项目中评估性欲亢进和无节制寻求他人的情况。使用荧光标记引物对AVPR1A重复序列进行微卫星基因分型，并通过激光诱导荧光进行检测。等位基因在半自动等位基因分型软件的辅助下确定。对于GATA重复序列，有32个完整的生物学三联体（28个信息丰富的家庭）；对于复合重复序列，有34个完整的生物学三联体（30个信息丰富的家庭）。使用病例对照和基于家族的关联方法对数据进行分析。
使用传递不平衡检验，AVPR1A GATA或复合重复序列对于性欲亢进或无节制寻求他人的优先传递并不显著。同样，病例对照分析未发现性欲亢进或无节制寻求他人与AVPR1A GATA或复合重复序列数量之间存在显著关联。对于p < 0.05，在基于家族的分析中，等位基因频率分别为0.1和0.5时，检测比值比为5.0和4.0的功效约为80%；在病例对照分析中，检测比值比为3.5和2.6的功效约为80%。
不支持AVPR1A优先传递给性欲亢进或无节制寻求他人的先证者。
