Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region.
Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region.
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DOI：
10.1038/s41398-021-01242-9
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发表时间：
2021-02-11
影响因子：
6.8
通讯作者：
Iwamoto K
中科院分区：
文献类型：
--
作者：
Ikegame T;Hidaka Y;Nakachi Y;Murata Y;Watanabe R;Sugawara H;Asai T;Kiyota E;Saito T;Ikeda M;Sasaki T;Hashimoto M;Ishikawa T;Takebayashi M;Iwata N;Kakiuchi C;Kato T;Kasai K;Bundo M;Iwamoto K
SLC 6A 4编码5-羟色胺转运蛋白，具有称为5-羟色胺转运蛋白连锁多态性区域（5-HTTLPR）的功能多态性。5-HTTLPR由短（S）和长（L）等位基因组成，每个等位基因具有14或16个串联重复。此外，在5-HTTLPR中还报道了extralong（XL）和其他罕见等位基因。虽然它们在亚洲人和非洲人中比在其他人群中更常见，但变异程度和等位基因频率（AF）并未在大人群中得到解决。在这里，我们报告了由两个队列组成的大量日本受试者（N = 2894）中罕见等位基因的AF。第一个队列（病例对照研究集，CCSS）包括1366名受试者，包括485名对照和881名精神病患者（双相情感障碍或精神分裂症）。第二个队列（Arao队列研究集，ACSS）由1528例老年受试者组成。在基因分型过程中，我们发现了11个新的5-HTTLPR等位基因，包括3个XL等位基因。一个新的等位基因有史以来最长的亚基报告，由28个串联重复。我们将其命名为XL 28-A。体外荧光素酶测定显示XL 28-A没有转录活性。XL 28-A在CCSS中的两名不相关的双相情感障碍患者和ACSS中的一名健康受试者中被发现，他们没有表现出抑郁症状或认知功能下降。因此，XL 28-A不太可能与精神疾病相关，尽管其明显的功能缺陷。我们的研究结果表明，解开5-HTTLPR复杂的遗传变异将是重要的，进一步了解其在精神疾病中的作用。
SLC6A4, which encodes the serotonin transporter, has a functional polymorphism called the serotonin transporter-linked polymorphic region (5-HTTLPR). The 5-HTTLPR consists of short (S) and long (L) alleles, each of which has 14 or 16 tandem repeats. In addition, the extralong (XL) and other rare alleles have been reported in 5-HTTLPR. Although they are more frequent in Asian and African than in other populations, the extent of variations and allele frequencies (AFs) were not addressed in a large population. Here, we report the AFs of the rare alleles in a large number of Japanese subjects (N = 2894) consisting of two cohorts. The first cohort (case-control study set, CCSS) consisted of 1366 subjects, including 485 controls and 881 patients with psychosis (bipolar disorder or schizophrenia). The second cohort (the Arao cohort study set, ACSS) consisted of 1528 elderly subjects. During genotyping, we identified 11 novel 5-HTTLPR alleles, including 3 XL alleles. One novel allele had the longest subunit ever reported, consisting of 28 tandem repeats. We named this XL28-A. An in vitro luciferase assay revealed that XL28-A has no transcriptional activity. XL28-A was found in two unrelated patients with bipolar disorder in the CCSS and one healthy subject in the ACSS who did not show depressive symptoms or a decline in cognitive function. Therefore, it is unlikely that XL28-A is associated with psychiatric disorders, despite its apparent functional deficit. Our results suggest that unraveling the complex genetic variations of 5-HTTLPR will be important for further understanding its role in psychiatric disorders.
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影响因子：
6.8
作者：
Avula R;Rand A;Black JL;O'Kane DJ
通讯作者：
O'Kane DJ
影响因子：
10.6
作者：
Munafo, Marcus R.;Durrant, Caroline;Flint, Jonathan
通讯作者：
Flint, Jonathan
影响因子：
2.5
作者：
Ivorra, J. L.;D'Souza, U. M.;Molto, M. D.
通讯作者：
Molto, M. D.
影响因子：
5.3
作者：
Gelernter, J;Kranzler, H;Cubells, JF
通讯作者：
Cubells, JF
影响因子：
0.9
作者：
Frisch, A;Finkel, B;Weizman, R
通讯作者：
Weizman, R