Maternal cardiovascular-related single nucleotide polymorphisms, genes, and pathways associated with early-onset preeclampsia
Autoři:
Paula Benny aff001; Kelly Yamasato aff002; Breck Yunits aff001; Xun Zhu aff003; Travers Ching aff003; Lana X. Garmire aff004; Marla J. Berry aff005; Dena Towner aff002
Působiště autorů:
University of Hawaii Cancer Center, Honolulu, Hawai’i, United States of America
aff001; Department of Obstetrics, Gynecology, and Women’s Health, John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawai’i, United States of America
aff002; Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, Hawai’i, United States of America
aff003; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America
aff004; Department of Cell and Molecular Biology, John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawai’i, United States of America
aff005
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0222672
Souhrn
Introduction
Preeclampsia is a medical condition complicated with hypertension and proteinuria during pregnancy. While preeclampsia affects approximately 5% of pregnancies, it remains without a cure. In addition, women who had preeclampsia during pregnancy have been reported to have an increased risk for cardiovascular disease later in life. However, the disease etiology and molecular mechanisms remain poorly understood. The paucity in the literature on preeclampsia associated maternal cardiovascular risk in different ethnic populations also present a need for more research. Therefore, the objective of this study was to identify cardiovascular/metabolic single nucleotide polymorphisms (SNPs), genes, and regulatory pathways associated with early-onset preeclampsia.
Materials and methods
We compared maternal DNAs from 31 women with early-onset preeclampsia with those from a control group of 29 women without preeclampsia who delivered full-term normal birthweight infants. Women with multiple gestations and/or known medical disorders associated with preeclampsia (pregestational diabetes, chronic hypertension, renal disease, hyperthyroidism, and lupus) were excluded. The MetaboChip genotyping array with approximately 197,000 SNPs associated with metabolic and cardiovascular traits was used. Single nucleotide polymorphism analysis was performed using the SNPAssoc program in R. The Truncated Product Method was used to identify significantly associated genes. Ingenuity Pathway Analysis and Ingenuity Causal Network Analysis were used to identify significantly associated disease processes and regulatory gene networks respectively.
Results
The early-onset preeclampsia group included 45% Filipino, 26% White, 16% other Asian, and 13% Native Hawaiian and other Pacific Islanders, which did not differ from the control group. There were no SNPs associated with early-onset preeclampsia after correction for multiple comparisons. However, through gene-based tests, 68 genes and 23 cardiovascular disease-related processes were found to be significantly associated. Associated gene regulatory networks involved cellular movement, cardiovascular disease, and inflammatory disease.
Conclusions
Multiple cardiovascular genes and diseases demonstrate associations with early-onset preeclampsia. This unfolds new areas of research regarding the genetic determinants of early-onset preeclampsia and their relation to future cardiovascular disease.
Klíčová slova:
Genetic networks – Human genetics – Hypertension – Cardiovascular diseases – Genetics of disease – Preeclampsia – Gene regulatory networks – Genetic predisposition
Zdroje
1. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130–7. doi: 10.1053/j.semperi.2009.02.010 19464502
2. Steegers E, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376:633–44.
3. Cnattingius S, Reilly M, Pawitan Y, Lichtenstein P. Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study. Am J Med Genet A. 2004;130A(4):365–71. doi: 10.1002/ajmg.a.30257 15384082
4. Chappell S, Morgan L. Searching for genetic clues to the causes of pre-eclampsia. Clin Sci. 2006;110(4):443–58. doi: 10.1042/CS20050323 16526948
5. Nishizawa H, Pryor-Koishi K, Kato T, Kowa H, Kurahashi H, Udagawa Y. Microarray analysis of differentially expressed fetal genes in placental tissue derived form early and late onset severe-preeclampsia. Placenta. 2007;28(5–6):487–97. doi: 10.1016/j.placenta.2006.05.010 16860862
6. Bendetto C, Marozio L, Ciccone G, Ghieppa G, Quaglia M, Matullo G. Synergistic effect of renin-angiotensin system and nitric oxide synthase genes polymorphisms in pre-eclampsia. Acta Obstetrica et Gynecologica. 2007;86(6):678–82.
7. Nakagawa K, Lim E, Harvey S, Miyamura J, Juarez DT. Racial/Ethnic Disparities in the Association Between Preeclampsia Risk Factors and Preeclampsia Among Women Residing in Hawaii. Matern Child Health J. 2016;20(9):1814–24. doi: 10.1007/s10995-016-1984-2 27000850
8. Ching T, Ha J, Song MA, Tiirikainen M, Molnar J, Berry M, et al. Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia. Clin Epigenetics. 2015;7(1):21.
9. Ching T, Song M, Tiirikainen M, Molnar J, Berry M, Towner D, et al. Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia. Mol Hum Reprod. 2014;20(9):885–904. doi: 10.1093/molehr/gau046 24944161
10. University of Hawaii John A Burns School of Medicine. University of Hawaii Biorepository 2014 [cited 19 March 2018]. http://uhbio.jabsom.hawaii.edu/Home.html.
11. Voight B, Kang HM, Ding J, Palmer CD, Sidore C, Chines PS et al. The Metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits. PLoS Genet 2012;8(8):e1002793. doi: 10.1371/journal.pgen.1002793 22876189
12. Gonzalez J, Armengol L, Sole X, Guino E, Mercader JM, Estivill X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007;23(5):644–5. doi: 10.1093/bioinformatics/btm025 17267436
13. Wojcik G, Kao WHL, Duggal P. Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies. BMC Genet. 2015;16:34. doi: 10.1186/s12863-015-0191-2 25887572
14. Gene. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information [cited 3 February 2016]. http://www.ncbi.nlm.nih.gov/gene.
15. Brown M, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol. 2013;28(1):1–19. doi: 10.1007/s10654-013-9762-6 23397514
16. Bellamy L, Casas J, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br Med J. 2007;335(7627):974.
17. Zhang G, Zhao J, Yi J, Luan Y, Wang Q. Association Between Gene Polymorphisms on Chromosome 1 and Susceptibility to Pre-Eclampsia: An Updated Meta-Analysis. Med Sci Monit. 2016;22:2202–14. doi: 10.12659/MSM.896552 27348238
18. Sharma S, Yadav S, Chandiok K, Sharma RS, Mishra V, Saraswathy KN. Protein signatures linking history of miscarriages and metabolic syndrome: a proteomic study among North Indian women. PeerJ. 2019;7:e6321. doi: 10.7717/peerj.6321 30783564
19. Mishra J, Talwar S, Kaur L, Chandiok K, Yadav S, Puri M, et al. Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India. Gene. 2019;704:68–73. doi: 10.1016/j.gene.2019.04.036 30986448
20. Holobotovskyy V, Chong YS, Burchell J, He B, Phillips M, Leader L, et al. Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia. Sci Transl Med. 2015;7(290):290ra88. doi: 10.1126/scitranslmed.aaa5038 26041705
21. Shaarawy M, El Meleigy M, Rasheed K. Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a potential biomarker for the assessment of disease severity and fetal outcome. J Soc Gynecol Investig. 2001;8(1):27–31. 11223354
22. Liu L, Zhang M, Min X, Cai L. Low Serum Levels of ABCA1, an ATP-Binding Cassette Transporter, Are Predictive of Preeclampsia. Tohoku J Exp Med. 2015;236(2):89–95. doi: 10.1620/tjem.236.89 26004638
23. Rani U, Praveen Kumar KS, Munisamaiah M, Rajesh D, Balakrishna S. Atrial fibrillation associated genetic variation near PITX2 gene increases the risk of preeclampsia. Pregnancy Hypertens. 2018;13:214–7. doi: 10.1016/j.preghy.2018.06.023 30177054
24. Loset M, Johnson MP, Melton PE, Ang W, Huang RC, Mori TA, et al. Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22. Pregnancy Hypertens. 2014;4:178–85. doi: 10.1016/j.preghy.2014.03.005 26104425
25. Johnson MP, Brennecke SP, East CE, Dyer TD, Roten LT, Proffitt JM, et al. Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease. Mol Hum Reprod. 2013;19(7):423–37. doi: 10.1093/molehr/gat011 23420841
26. Tuteja G, Cheng E, Papadakis H, Bejerano G. PESNPdb: A comprehensive database for SNPs studied in association with pre-eclampsia. Placenta. 2012;33(12):1055–57. doi: 10.1016/j.placenta.2012.09.016 23084601
27. Kaartokallio T, Cervera A, Kyllonen A, Laivuori K, Group. FCI. Gene expression profiling of pre-eclamptic placentae by RNA sequencing. Sci Rep. 2015;5:14107. doi: 10.1038/srep14107 26388242
28. Kleinrouweler CE, van Uitert M, Moerland PD, Ris-Stalpers C, van der Post JA, Afink GB. Differentially expressed genes in the pre-eclamptic placenta: a systematic review and meta-analysis. PLoS One. 2013;8(7):e68991. doi: 10.1371/journal.pone.0068991 23874842
29. Kawasaki K, Kondoh E, Chigusa Y, Ujita M, Murakami R, Mogami H, et al. Reliable pre-eclampsia pathways based on multiple independent microarray data sets. Mol Hum Reprod. 2015;21(2):217–24. doi: 10.1093/molehr/gau096 25323968
30. Sitras V, Fenton C, Acharya G. Gene expression profile in cardiovascular disease and preeclampsia: A meta-analysis of the transcriptome based on raw data from human studies deposited in Gene Expression Omnibus. Placenta. 2015;36(2):170–8. doi: 10.1016/j.placenta.2014.11.017 25555499
31. Murphy MSQ, Bytautiene E, Saade G, Smith GN. Alterations to the maternal circulating proteome after pre-eclampsia. Am J Obstet Gynecol. 2015;213:853.e1–9.
32. Vance C, Taylor RN, Craven TE, Edwards MS, Corriere MA. Increased prevalence of preeclampsia among women undergoing procedural intervention for renal artery fibromuscular dysplasia. Ann Vasc Surg. 2015;29(6):1105–10. doi: 10.1016/j.avsg.2015.03.037 26004957
33. Gordon J, Kahn AM, Burns JC. When children with Kawasaki disease grow up: Myocardial and vascular complications in adulthood. J Am Coll Cardiol. 2009;54(21):1911–20. doi: 10.1016/j.jacc.2009.04.102 19909870
34. Oudejans C, van Dijk M, Oosterkamp M, Lachmeijer A, Blankenstein MA. Genetics of preeclampsia: paradigm shifts. Hum Genet. 2007;120(5):2007.
35. Stekkinger E, Zandstra M, Peeters LLH, Spaanderman MEA. Early-onset preeclampsia and the prevalence of postpartum metabolic syndrome. Obstet Gynecol. 2009;114(5):1076–84. doi: 10.1097/AOG.0b013e3181b7b242 20168110
36. Boyd H, Tahir H, Wohlfahrt J, Melbye M. Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia. Am J Epidemiol. 2013;178(11):1611–9. doi: 10.1093/aje/kwt189 24049162
37. Ramalingam U, Forsyth SJ, Struthers AD, Fraser CG, Godfrey V, Murphy DJ. Polymorphisms of the angiotensin converting enzyme gene in early-onset and late-onset pre-eclampsia. J Matern Fetal Neonatal Med. 2010;23(8):874–9. doi: 10.3109/14767050903456667 20044877
38. Rao A, Daniels K, El-Sayed YY, Moshesh MK, Caughey AB. Perinatal outcomes among Asian American and Pacific Islander women. Am J Obstet Gynecol. 2006;195(3):834–8. doi: 10.1016/j.ajog.2006.06.079 16949421
39. Sun C, Zhang L, Zhang WY. Gene expression profiling of maternal blood in early onset severe preeclampsia: identification of novel biomarkers. J Perinat Med. 2009;37(6):609–16. doi: 10.1515/JPM.2009.103 19681734
Článok vyšiel v časopise
PLOS One
2019 Číslo 9
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Úspěšná resuscitativní thorakotomie v přednemocniční neodkladné péči
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania