Study Report
Reference
| Citation | Philibert, 2008 PubMed |
| Full Info | Philibert, R.A., Sandhu, H., Hollenbeck, N., Gunter, T., Adams, W. and Madan, A. (2008) The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B Neuropsychiatr Genet, 147B, 543-549.
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Study
| Hypothesis or Background |
Serotonin Transporter (5HTT or SLC6A4) mRNA transcription is regulated by both genetic and epigenetic mechanisms. Unfortunately, despite intense scrutiny, the exact identity and contribution of each of these regulatory mechanisms, and their relationship to behavioral illness remain unknown. This lack of knowledge is critical because alterations in SLC6A4 function are posited to be central to a wide variety of CNS disorders.
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| Sample Information | subjects who participated in the latest wave of the Iowa Adoption Studies |
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| Method Detail | In order to address this shortcoming, we quantified 5HTTLPR genotype, SLC6A4 mRNA production and CpG methylation using biomaterial from 192 lymphoblast cell lines derived from subjects who participated in the latest wave of the Iowa Adoption Studies. We then analyzed the resulting data with respect to clinical characteristics. |
| Method Keywords | genotyping; DNA methylation analysis |
| Result | We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the Long G allele on mRNA transcription. We also found that CpG methylation was higher (P < 0.0008) and mRNA production (P < 0.0001) was lower in females as compared to males. Those subjects with a lifetime history of Alcohol Dependence had higher levels of SLC6A4 mRNA. There was a trend for an association of increased overall methylation with lifetime history of major depression. Finally, we confirm our prior findings that the exact levels of 5HTT mRNA expression are dependent on how it is measured. |
| Conclusions | We conclude that both genetic variation and epigenetic modifications contribute to the regulation of SLC6A4 function and that more in-depth studies of the molecular mechanisms controlling gene activity and the relationship of these mechanisms to behavioral illness are indicated. |
Relationships reported by
Philibert, 2008
| Component A Approved Name (Name in Paper) |
Component A Type |
Component B Approved Name (Name in Paper) |
Component B Type |
Statistical Result |
Relationship Description |
Result Category (Positive/Negative)) |
|
MDD
|
syndrome |
methylation-SLC6A4-17987668 (methylation-SLC6A4-17987668) |
epigenetic site |
P<0.07 |
There was a trend for those without a lifetime history of MD, but not AD, to have higher amounts of total methylation than those without a history of depression (P<0.07; ANOVA; 17.3% in those with MD vs. 15.6% in those without MD). |
Negative
|
|
MDD
|
syndrome |
SLC6A4 (5HTTLPR) |
gene |
P-value < 0.0001 |
We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the Long G allele on mRNA transcription. We also found that CpG methylation was higher (P < 0.0008) and mRNA production (P < 0.0001) was lower in females as compared to males. |
Positive
|
