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Open Access Research article

Association of COMT genotypes with S-COMT promoter methylation in growth-discordant monozygotic twins and healthy adults

Felix Schreiner1, Osman El-Maarri2, Bettina Gohlke1, Sonja Stutte1, Nicole Nuesgen2, Manuel Mattheisen3, Rolf Fimmers3, Peter Bartmann4, Johannes Oldenburg2 and Joachim Woelfle1*

Author Affiliations

1 Pediatric Endocrinology Division, Children's Hospital, University of Bonn, Adenauerallee 119, Bonn 53113, Germany

2 Institute for Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud-Str. 25, Bonn, 53127, Germany

3 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, Bonn, 53127, Germany

4 Department of Neonatology, Children's Hospital, University of Bonn, Adenauerallee 119, Bonn 53113, Germany

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BMC Medical Genetics 2011, 12:115  doi:10.1186/1471-2350-12-115

Published: 1 September 2011

Abstract

Background

Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and estrogen metabolism. Recently, COMT haplotypes rather than the single polymorphism Val158Met have been reported to underlie differences in protein expression by modulating mRNA secondary structure. So far, studies investigating the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly focused on phenotypical aspects, and results have been controversial.

Methods

We assessed S-COMT promoter methylation in saliva and blood derived DNA with regard to early pre- and postnatal growth as well as to genotype for polymorphisms rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4 years), who were discordant for intrauterine development due to severe feto-fetal-transfusion syndrome. Methylation levels of two previously reported partially methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP HPLC) assay.

Results

Overall, we observed a high variability of S-COMT promoter methylation, which did not correlate with individual differences in the pre- or postnatal growth pattern. Within the twin pairs however we noted a distinct similarity that could be linked to underlying COMT genotypes. This association was subsequently confirmed in a cohort of 93 unrelated adult controls. Interestingly, 158Val-alleles were found at both ends of the epigenotypical range, which is in accordance with a recently proposed model of COMT haplotypes corresponding to a continuum of phenotypical variability.

Conclusion

The strong heritable component of S-COMT promoter methylation found in our study needs to be considered in future approaches that focus on interactions between COMT epigenotype and phenotype.