Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22

Mari Løset; Matthew P. Johnson; Phillip E. Melton; Wei Ang; Rae Chi Huang; Trevor A. Mori; Lawrence J. Beilin; Craig Pennell; Linda T. Roten; Ann Charlotte Iversen; Rigmor Austgulen; Christine E. East; John Blangero; Shaun P. Brennecke; Eric K. Moses

doi:10.1016/j.preghy.2014.03.005

Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22

Mari Løset, Matthew P. Johnson, Phillip E. Melton, Wei Ang, Rae Chi Huang, Trevor A. Mori, Lawrence J. Beilin, Craig Pennell, Linda T. Roten, Ann Charlotte Iversen, Rigmor Austgulen, Christine E. East, John Blangero, Shaun P. Brennecke, Eric K. Moses

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Objective Four putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort. Methods The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software. Results Nominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033). Conclusions Our collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).

Original language	English (US)
Pages (from-to)	178-185
Number of pages	8
Journal	Pregnancy Hypertension
Volume	4
Issue number	2
DOIs	https://doi.org/10.1016/j.preghy.2014.03.005
State	Published - Apr 2014
Externally published	Yes

Keywords

2q22
Cardiovascular disease (CVD)
Genetic association
Preeclampsia
Raine Study

ASJC Scopus subject areas

Internal Medicine
Obstetrics and Gynecology

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10.1016/j.preghy.2014.03.005

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Løset, M., Johnson, M. P., Melton, P. E., Ang, W., Huang, R. C., Mori, T. A., Beilin, L. J., Pennell, C., Roten, L. T., Iversen, A. C., Austgulen, R., East, C. E., Blangero, J., Brennecke, S. P., & Moses, E. K. (2014). Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22. Pregnancy Hypertension, 4(2), 178-185. https://doi.org/10.1016/j.preghy.2014.03.005

@article{b33b3f6f75234594bef491f99071c5cf,

title = "Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22",

abstract = "Objective Four putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort. Methods The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software. Results Nominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033). Conclusions Our collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).",

keywords = "2q22, Cardiovascular disease (CVD), Genetic association, Preeclampsia, Raine Study",

author = "Mari L{\o}set and Johnson, {Matthew P.} and Melton, {Phillip E.} and Wei Ang and Huang, {Rae Chi} and Mori, {Trevor A.} and Beilin, {Lawrence J.} and Craig Pennell and Roten, {Linda T.} and Iversen, {Ann Charlotte} and Rigmor Austgulen and East, {Christine E.} and John Blangero and Brennecke, {Shaun P.} and Moses, {Eric K.}",

note = "Funding Information: This study was supported by grants from the Norwegian University of Science and Technology (NTNU) (M.L., A.C.I., R.A.), Liaison Committee between the Central Norway Regional Health Authority (RHA) and NTNU (L.T.R.). The Raine Study receives funding for core activities from The University of Western Australia , the Telethon Institute for Child Health Research , the Raine Medical Research Foundation , the Faculty of Medicine, Dentistry and Health Sciences ( UWA ), the Women and Infants Research Foundation and Curtin University . The 17-year follow-up assessment was supported by project grants from the Australian National Health and Medical Research Council (NHMRC) (ID 353514 ). Blood and DNA collection was supported by project grants from the NHMRC (Grant IDs 572613 and 403981 ). ",

year = "2014",

month = apr,

doi = "10.1016/j.preghy.2014.03.005",

language = "English (US)",

volume = "4",

pages = "178--185",

journal = "Pregnancy Hypertension",

issn = "2210-7789",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

T1 - Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22

AU - Løset, Mari

AU - Johnson, Matthew P.

AU - Melton, Phillip E.

AU - Ang, Wei

AU - Huang, Rae Chi

AU - Mori, Trevor A.

AU - Beilin, Lawrence J.

AU - Pennell, Craig

AU - Roten, Linda T.

AU - Iversen, Ann Charlotte

AU - Austgulen, Rigmor

AU - East, Christine E.

AU - Blangero, John

AU - Brennecke, Shaun P.

AU - Moses, Eric K.

N1 - Funding Information: This study was supported by grants from the Norwegian University of Science and Technology (NTNU) (M.L., A.C.I., R.A.), Liaison Committee between the Central Norway Regional Health Authority (RHA) and NTNU (L.T.R.). The Raine Study receives funding for core activities from The University of Western Australia , the Telethon Institute for Child Health Research , the Raine Medical Research Foundation , the Faculty of Medicine, Dentistry and Health Sciences ( UWA ), the Women and Infants Research Foundation and Curtin University . The 17-year follow-up assessment was supported by project grants from the Australian National Health and Medical Research Council (NHMRC) (ID 353514 ). Blood and DNA collection was supported by project grants from the NHMRC (Grant IDs 572613 and 403981 ).

PY - 2014/4

Y1 - 2014/4

N2 - Objective Four putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort. Methods The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software. Results Nominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033). Conclusions Our collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).

AB - Objective Four putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort. Methods The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software. Results Nominal associations (P < 0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P = 0.005) and decreased blood glucose levels in adolescents (P = 0.022). The LRP1B SNP was associated with increased maternal height (P = 0.026) and decreased maternal weight (P = 0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P = 0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P = 0.003) and having a mother with prior preeclamptic pregnancy (P = 0.033). Conclusions Our collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P < 0.001).

KW - 2q22

KW - Cardiovascular disease (CVD)

KW - Genetic association

KW - Preeclampsia

KW - Raine Study

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U2 - 10.1016/j.preghy.2014.03.005

DO - 10.1016/j.preghy.2014.03.005

M3 - Article

C2 - 26104425

AN - SCOPUS:84899908548

SN - 2210-7789

VL - 4

SP - 178

EP - 185

JO - Pregnancy Hypertension

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IS - 2

ER -

Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22

Abstract

Keywords

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