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TERT rs2736100 和 TERC rs16847897 基因型可调节乌干达 HIV+儿童和青少年内化性精神障碍与端粒长度加速损耗之间的关联。

TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda.

机构信息

Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

Mental Health Section, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.

出版信息

BMC Med Genomics. 2021 Jan 6;14(1):15. doi: 10.1186/s12920-020-00857-z.

Abstract

BACKGROUND

Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years).

RESULTS

We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months.

CONCLUSIONS

TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.

摘要

背景

内化精神障碍(IMD)(抑郁、焦虑和创伤后应激障碍)与端粒长度(TL)加速损耗有关;然而,在遗传变异影响 TL 的背景下,尚未对此关联进行研究。我们之前报告了在乌干达 HIV+儿童和青少年中 IMD 与 TL 加速损耗之间的关联。本研究调查了端粒酶逆转录酶基因(TERT)(rs2736100、rs7726159、rs10069690 和 rs2853669)和端粒酶 RNA 成分基因(TERC)(rs12696304、rs16847897 和 rs10936599)中选定的单核苷酸多态性对 IMD 和 TL 之间的关联的调节作用,这些 SNP 存在于乌干达 HIV+儿童(5-11 岁)和青少年(12-17 岁)中。

结果

我们没有发现 IMD 作为一个组与任何选定的 SNPs 之间的相互作用与 TL 在基线时存在显著差异。我们观察到 IMDs 与 TERT rs2736100(p=0.007)和 TERC rs16847897(p=0.012)之间存在显著相互作用,分别为 TL 在 12 个月时的相互作用。

结论

TERT rs2736100 和 TERC rs16847897 调节了乌干达 HIV+儿童和青少年中 IMD 和 TL 之间的关联在 12 个月时。了解这种关联的性质可能有助于阐明 IMD 中晚期细胞衰老的病理生理机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e89/7789327/03c0d63d6346/12920_2020_857_Fig1_HTML.jpg

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