Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia
Pre-eclampsia is a common serious disorder of human pregnancy, which is associated with significant maternal and perinatal morbidity and mortality. The suspected aetiology of pre-eclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic compon...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Published: |
2009
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| Online Access: | http://hdl.handle.net/20.500.11937/6655 |
| _version_ | 1848745139938263040 |
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| author | Fitzpatrick, E. Johnson, M. Dyer, T. Forrest, S. Elliott, K. Blangero, J. Brennecke, S. Moses, Eric |
| author_facet | Fitzpatrick, E. Johnson, M. Dyer, T. Forrest, S. Elliott, K. Blangero, J. Brennecke, S. Moses, Eric |
| author_sort | Fitzpatrick, E. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Pre-eclampsia is a common serious disorder of human pregnancy, which is associated with significant maternal and perinatal morbidity and mortality. The suspected aetiology of pre-eclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Recently, we reported significant linkage to chromosome 2q22 in 34 Australian/New Zealand (Aust/NZ) pre-eclampsia/ eclampsia families, and activin A receptor type IIA (ACVR2A) was identified as a strong positional candidate gene at this locus. In an attempt to identify the putative risk variants, we have now comprehensively re-sequenced the entire coding region of the ACVR2A gene and the conserved non-coding sequences in a subset of 16 individuals from these families. We identified 45 single nucleotide polymorphisms (SNPs), with 9 being novel. These SNPs were genotyped in our total family sample of 480 individuals from 74 Aust/NZ pre-eclampsia families (including the original 34 genome-scanned families). Our best associations between ACVR2A polymorphisms and pre-eclampsia were for rs10497025 (P = 0.025), rs13430086 (P = 0.010) and three novel SNPs: LF004, LF013 and LF020 (all with P = 0.018). After correction for multiple hypothesis testing, none of these associations reached significance (P > 0.05). Based on these data, it remains unclear what role, if any, ACVR2A polymorphisms play in pre-eclampsia risk, at least in these Australian families. However, it would be premature to rule out this gene as significant associations between ACVR2A SNPs and pre-eclampsia have recently been reported in a large Norwegian (HUNT) population sample. © The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. |
| first_indexed | 2025-11-14T06:12:37Z |
| format | Journal Article |
| id | curtin-20.500.11937-6655 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:12:37Z |
| publishDate | 2009 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-66552017-09-13T14:36:24Z Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia Fitzpatrick, E. Johnson, M. Dyer, T. Forrest, S. Elliott, K. Blangero, J. Brennecke, S. Moses, Eric Pre-eclampsia is a common serious disorder of human pregnancy, which is associated with significant maternal and perinatal morbidity and mortality. The suspected aetiology of pre-eclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Recently, we reported significant linkage to chromosome 2q22 in 34 Australian/New Zealand (Aust/NZ) pre-eclampsia/ eclampsia families, and activin A receptor type IIA (ACVR2A) was identified as a strong positional candidate gene at this locus. In an attempt to identify the putative risk variants, we have now comprehensively re-sequenced the entire coding region of the ACVR2A gene and the conserved non-coding sequences in a subset of 16 individuals from these families. We identified 45 single nucleotide polymorphisms (SNPs), with 9 being novel. These SNPs were genotyped in our total family sample of 480 individuals from 74 Aust/NZ pre-eclampsia families (including the original 34 genome-scanned families). Our best associations between ACVR2A polymorphisms and pre-eclampsia were for rs10497025 (P = 0.025), rs13430086 (P = 0.010) and three novel SNPs: LF004, LF013 and LF020 (all with P = 0.018). After correction for multiple hypothesis testing, none of these associations reached significance (P > 0.05). Based on these data, it remains unclear what role, if any, ACVR2A polymorphisms play in pre-eclampsia risk, at least in these Australian families. However, it would be premature to rule out this gene as significant associations between ACVR2A SNPs and pre-eclampsia have recently been reported in a large Norwegian (HUNT) population sample. © The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 2009 Journal Article http://hdl.handle.net/20.500.11937/6655 10.1093/molehr/gap001 unknown |
| spellingShingle | Fitzpatrick, E. Johnson, M. Dyer, T. Forrest, S. Elliott, K. Blangero, J. Brennecke, S. Moses, Eric Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia |
| title | Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia |
| title_full | Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia |
| title_fullStr | Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia |
| title_full_unstemmed | Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia |
| title_short | Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia |
| title_sort | genetic association of the activin a receptor gene (acvr2a) and pre-eclampsia |
| url | http://hdl.handle.net/20.500.11937/6655 |