A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)

L. T. Roten; M. H. Fenstad; S. Forsmo; M. P. Johnson; E. K. Moses; R. Austgulen; F. Skorpen

doi:10.1093/molehr/gar014

A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)

L. T. Roten, M. H. Fenstad, S. Forsmo, M. P. Johnson, E. K. Moses, R. Austgulen, F. Skorpen

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37 Scopus citations

Abstract

The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine and estrogen degradation and has recently been ascribed a role in development of preeclampsia. In the present study, we have examined the COMT gene by genotyping the functional Val108/158Met polymorphism (rs4680) and an additional single-nucleotide polymorphism, rs6269, predicting COMT activity haplotypes in a large Norwegian case/control cohort (n_cases = 1135, n_controls= 2262). A low COMT activity haplotype is associated with recurrent preeclampsia in our cohort. This may support the role of redox-regulated signaling and oxidative stress in preeclampsia pathogenesis as suggested by recent studies in a genetic mouse model. The COMT gene might be a genetic risk factor shared between preeclampsia and cardiovascular diseases.

Original language	English (US)
Article number	gar014
Pages (from-to)	439-446
Number of pages	8
Journal	Molecular Human Reproduction
Volume	17
Issue number	7
DOIs	https://doi.org/10.1093/molehr/gar014
State	Published - Jul 2011

Keywords

158Met
COMT
Catechol-O-methyltransferase
Haplotypes
Preeclampsia
Val108

ASJC Scopus subject areas

Reproductive Medicine
Embryology
Molecular Biology
Genetics
Obstetrics and Gynecology
Developmental Biology
Cell Biology

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title = "A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)",

abstract = "The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine and estrogen degradation and has recently been ascribed a role in development of preeclampsia. In the present study, we have examined the COMT gene by genotyping the functional Val108/158Met polymorphism (rs4680) and an additional single-nucleotide polymorphism, rs6269, predicting COMT activity haplotypes in a large Norwegian case/control cohort (ncases = 1135, ncontrols= 2262). A low COMT activity haplotype is associated with recurrent preeclampsia in our cohort. This may support the role of redox-regulated signaling and oxidative stress in preeclampsia pathogenesis as suggested by recent studies in a genetic mouse model. The COMT gene might be a genetic risk factor shared between preeclampsia and cardiovascular diseases.",

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note = "Funding Information: This work was supported by grants from the Liaison Committee of NTNU and Central Norway Regional Health Authority (L.T.R. and M.H.F.). Funding to pay the Open Access publication charges for this article was provided by the Liaison Committee of NTNU and Central Norway Regional Health Authority. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",

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AU - Johnson, M. P.

AU - Moses, E. K.

AU - Austgulen, R.

AU - Skorpen, F.

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N2 - The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine and estrogen degradation and has recently been ascribed a role in development of preeclampsia. In the present study, we have examined the COMT gene by genotyping the functional Val108/158Met polymorphism (rs4680) and an additional single-nucleotide polymorphism, rs6269, predicting COMT activity haplotypes in a large Norwegian case/control cohort (ncases = 1135, ncontrols= 2262). A low COMT activity haplotype is associated with recurrent preeclampsia in our cohort. This may support the role of redox-regulated signaling and oxidative stress in preeclampsia pathogenesis as suggested by recent studies in a genetic mouse model. The COMT gene might be a genetic risk factor shared between preeclampsia and cardiovascular diseases.

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A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)

Abstract

Keywords

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