Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island

被引:145
作者
Philibert, Robert
Madan, Anup
Andersen, Allan
Cadoret, Remi
Packer, Hans
Sandhu, Harinder
机构
[1] Univ Iowa, Psychiat Res MEB, Dept Psychiat, Iowa City, IA USA
[2] Univ Iowa, Psychiat Res MEB, Neurosci Program, Iowa City, IA USA
[3] Univ Iowa, Psychiat Res MEB, Dept Neurosurg, Iowa City, IA USA
关键词
serotonin transporter; methylation; epigenetics; promoter;
D O I
10.1002/ajmg.b.30414
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The serotonin reuptake transporter (5HTT) is thought to be the principal regulator of serotonergic activity and epigenetic effects at this locus are thought to be important moderators of vulnerability to neuropsychiatric illness. In attempt to understand the basis of this regulation, several gene polymorphisms that affect 5HTT mRNA levels have been described. But to date, no clear mechanism linking these polymorphisms to vulnerability to epigenetic effects have been described. In this communication, we describe a CpG island in the 5' region of the 5HTT gene that contains an alternative exon 1 and possible promoter for 5HTT. We then confirm the existence of this transcript and ascertain the methylation status of this CpG island in 49 lymphoblast cell lines and analyze the relationship between methylation and 5HTT mRNA levels. We demonstrate that methylation at this CpG island is associated with decreased levels of 5HTT mRNA, but that this effect is evident only when 5HTTLPR genotype is taken into account. We suggest that these findings have significant implications for the understanding of the role of this locus in behavioral illness. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:101 / 105
页数:5
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