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Preeclampsia risk, maternal 25-hydroxyvitamin D concentration, and variation in vitamin D metabolism pathway genes

Baca, Katharyn (2016) Preeclampsia risk, maternal 25-hydroxyvitamin D concentration, and variation in vitamin D metabolism pathway genes. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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OBJECTIVE: Our objectives were to study the relationships between 25-hydroxyvitamin D (25(OH)D) and preeclampsia risk, maternal genetic variation in 3 vitamin D metabolism genes (GC, CYP27B1, VDR) and preeclampsia risk, and variation in the same genes and 25(OH)D. METHODS: We used two racially diverse pregnancy cohorts (EVITA and Collaborative Perinatal Project (CPP)) to achieve these objectives. We estimated the association between log-transformed 25(OH)D and preeclampsia risk in EVITA by using log-binomial regression with restricted cubic splines. In EVITA and CPP, we used multivariable logistic and linear regression models to estimate the associations between allelic variation and preeclampsia risk, and genotype and log-transformed 25(OH)D, respectively. Meta-analyses were conducted to calculate estimates of association between and within cohorts. RESULTS: Dose-response associations of 25(OH)D were observed for both severe and mild preeclampsia. Trends of associations were observed in genetic variation and preeclampsia risk. Compared with major allele carriers, Black mothers in EVITA who carried the minor allele for rs11732451 GC single nucleotide polymorphism (SNP) and 2 VDR SNPs (rs4340112, rs10459217) had increased odds of preeclampsia, while the odds were lowered for those who carried the minor allele for 1 GC SNP (rs1099028) and 2 VDR SNPs(rs757344, rs12721364). In the meta-analysis, two VDR SNPs (rs886441 and rs2853561) had trends of decreased odds of preeclampsia for all Black mothers. For the 25(OH)D analysis, statistically significant associations were observed. Compared with those with major allele genotypes, mothers with minor allele genotypes of rs1844885 (GC) and rs11168275 (VDR) had increased 25(OH)D and of rs11732451 (GC) had lowered 25(OH)D. In the meta-analysis on all Black mothers, rs1844885 (GC) was associated with increased 25(OH)D while there was a trend of decreased 25(OH)D for rs10877016 (CYP27B1). CONCLUSIONS: Low 25(OH)D may be enough to reduce risk of preeclampsia. If our findings are confirmed in a replication study, genetic variation may be an independent risk factor for maternal 25(OH)D, making the findings of this research relevant to public health.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Baca, Katharynkasiambaca@gmail.comKMB192
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBodnar, Lisa M.bodnar@edc.pitt.eduLBODNAR
Committee MemberZmuda, Joseph M.zmudaj@edc.pitt.eduEPIDJMZ
Committee MemberMarazita, Mary Lmarazita@pitt.eduMARAZITA
Committee MemberSimhan, Hyagriv
Date: 28 January 2016
Date Type: Publication
Defense Date: 30 November 2015
Approval Date: 28 January 2016
Submission Date: 3 December 2015
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 134
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: vitamin D, preeclampsia, pregnancy, genetics, vitamin D metabolism, hypertension, Single nucleotide polymorphisms
Date Deposited: 28 Jan 2016 15:33
Last Modified: 01 Jan 2021 06:15


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