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血清素转运体(5-HTT)基因中的启动子多态性与汉族人群的白细胞端粒长度显著相关。

Promoter polymorphism in the serotonin transporter (5-HTT) gene is significantly associated with leukocyte telomere length in Han Chinese.

作者信息

Li Ping, Liu Tiantian, Liu Jiajia, Zhang Qing, Lou Fenglan, Kong Feng, Cheng Guanghui, Björkholm Magnus, Zheng Chengyun, Xu Dawei

机构信息

School of Nursing, Shandong University, Jinan, PR China.

Department of Microbiology, Shandong University School of Medicine, Jinan, PR China; Department of Medicine, Division of Hematology and Center for Molecular Medicine, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.

出版信息

PLoS One. 2014 Apr 7;9(4):e94442. doi: 10.1371/journal.pone.0094442. eCollection 2014.

Abstract

The serotonin transporter gene (5-HTT)-linked polymorphic region (5-HTTLPR) plays an important role in modulating mood and behavior by regulating 5-HTT expression and thereby controlling the concentration of serotonin (5-HT) in brain synapses: The homozygous shorter allele (S/S) in 5-HTTLPR results in lower 5-HTT expression coupled with stronger psycho-pathological reactions to stressful experiences compared to the homozygous long (L/L) and heterozygous (S/L) alleles. Psychological insults and mood disorders have been shown to cause accelerated telomere shortening, a marker of biological aging, however, it is currently unclear whether the allelic variants of 5-HTTLPR affect telomere length (TL) in the healthy population without mood disorders. In the present study, we determined the relationship between TL and the 5-HTTLPR variants in healthy Han Chinese. The 5-HTTLPR genotyping and leukocyte TL analysis of 280 young female Han Chinese freshmen showed a significantly shorter TL in 149 of them carrying the 5-HTTLPR S/S version compared to those (131) with the L/S or L/S plus L/L genotypes (mean ± SD, 0.533±0.241 for S/S vs 0.607±0.312 for L/S, P  =  0.034; or vs 0.604±0.313 for L/S plus L/L, P  =  0.038). Similar results were achieved in the other cohort including 220 adult healthy individuals of different age, gender and profession (0.691±0.168 for S/S vs 0.729±0.211 for L/S, P  =  0.046, or vs 0.725±0.213 for L/S plus L/L, P  =  0.039). Taken together, shorter leukocyte TL is significantly associated with the 5-HTTLPR S/S allelic variant, which may be implicated in psychological stress-related health problems.

摘要

血清素转运体基因(5-HTT)连锁多态性区域(5-HTTLPR)通过调节5-HTT表达,进而控制脑突触中血清素(5-HT)的浓度,在调节情绪和行为方面发挥重要作用:与纯合长等位基因(L/L)和杂合等位基因(S/L)相比,5-HTTLPR中的纯合短等位基因(S/S)导致5-HTT表达降低,同时对应激经历产生更强的心理病理反应。心理创伤和情绪障碍已被证明会导致端粒加速缩短,这是生物衰老的一个标志,然而,目前尚不清楚5-HTTLPR的等位基因变体是否会影响无情绪障碍的健康人群的端粒长度(TL)。在本研究中,我们确定了健康汉族人群中TL与5-HTTLPR变体之间的关系。对280名年轻汉族女性新生进行的5-HTTLPR基因分型和白细胞TL分析显示,与131名具有L/S或L/S加L/L基因型的个体相比,149名携带5-HTTLPR S/S型的个体的TL显著缩短(平均值±标准差,S/S型为0.533±0.241,L/S型为0.607±0.312,P = 0.034;或与L/S加L/L型的0.604±0.313相比,P = 0.038)。在另一个包括220名不同年龄、性别和职业的成年健康个体的队列中也得到了类似结果(S/S型为0.691±0.168,L/S型为0.729±0.211,P = 0.046;或与L/S加L/L型的0.725±0.213相比,P = 0.039)。综上所述,较短的白细胞TL与5-HTTLPR S/S等位基因变体显著相关,这可能与心理应激相关的健康问题有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb1/3978058/d9b2faf3abdc/pone.0094442.g001.jpg

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