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Abstract
Introduction: Preeclampsia is a common and partially genetic pregnancy complication characterized by hypertension and proteinuria. Association with cardiovascular disease and type 2 diabetes has been reported in 9p21 by several genome-wide association studies. It has been hypothesized that cardiometabolic diseases may share common etiology with preeclampsia.
Materials and methods: We tested association with the 9p21 region to preeclampsia in the Finnish population by genotyping 23 tagging single nucleotide polymorphisms (SNPs) in 15 extended preeclampsia families and in a nationwide cohort consisting of 281 cases and 349 matched controls. Replication was conducted in additional datasets.
Results: Four SNPs (rs7044859, rs496892, rs564398 and rs7865618) showed nominal association (p ≤ 0.024 uncorrected) with preeclampsia in the case-control cohort. To increase power, we genotyped two SNPs in additional 388 cases and 341 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Partial replication was also attempted in a UK cohort (237 cases and 199 controls) and in 74 preeclamptic families from Australia/New Zealand. We were unable to replicate the initial association in the extended Finnish dataset or in the two international cohorts.
Conclusions: Our study did not find evidence for the involvement of the 9p21 region in the risk of preeclampsia.
Chromosome 9p21 is not associated with preeclampsia.
Key Message
Acknowledgements
We sincerely thank all the participants and the support of all the clinicians, research midwives, researchers and technicians. We would like to express our thanks to Ms. Leena Järvinen for technical assistance with the Finnish family cohort.
Disclosure statement
The authors report no conflicts of interest. The funders did not participate in study design, analysis or reporting of the results.
Funding information
This study was supported by Academy of Finland; Finnish Medical Foundation, Jane and Aatos Erkko Foundation; Sigrid Jusélius Foundation, Päivikki and Sakari Sohlberg Foundation; Research Funds of the University of Helsinki; Government Special state subsidy for Health Sciences (EVO funding) at Helsinki and Uusimaa Hospital District.
Tea Kaartokallio was supported by Doctoral Programme in Biomedicine (DPBM), Doctoral Programme in Clinical Research (KLTO), Research Foundation of the University of Helsinki and Biomedicum Helsinki Foundation.
Ayat Sayed was supported by a grant from the Egyptian Ministry of Higher Education.
Elina Salmela was supported by Antti and Jenny Wihuri Foundation.
Tuuli Lappalainen was supported by Emil Aaltonen Foundation.
The Australian and New Zealand component of the study were funded by grants from the Australian National Health and Medical Research Council (# 1053152) and the National Institutes of Health of the USA (# HD049847).
Funding for the UK VIP (vitamins in pre-eclampsia) trial was provided by the Wellcome Trust.