Predicting the risk to develop preeclampsia in the first trimester combining promoter variant -98A/C of LGALS13 (placental protein 13), Black ethnicity, previous preeclampsia, obesity, and maternal age

Journal article


Madar-Shapiro, L., Karady, I., Trahtenherts, A., Syngelaki, A., Akolekar, R., Poon, L., Cohen, R., Sharabi-Nov, A., Huppertz, B., Sammar, M., Juhasz, K., Than, N.G., Papp, Z., Romero, R., Nicolaides, K.H. and Meiri, H. 2018. Predicting the risk to develop preeclampsia in the first trimester combining promoter variant -98A/C of LGALS13 (placental protein 13), Black ethnicity, previous preeclampsia, obesity, and maternal age. Fetal Diagnosis & Therapy. 43 (4), pp. 250-265.
AuthorsMadar-Shapiro, L., Karady, I., Trahtenherts, A., Syngelaki, A., Akolekar, R., Poon, L., Cohen, R., Sharabi-Nov, A., Huppertz, B., Sammar, M., Juhasz, K., Than, N.G., Papp, Z., Romero, R., Nicolaides, K.H. and Meiri, H.
Abstract

BACKGROUND: We studied LGALS13 [Placental Protein 13 (PP13)] promoter DNA polymorphisms in preeclampsia (PE) prediction, given PP13’s effects on hypotension, angiogenesis and immunotolerance.

METHODS: We retrieved 67 PE (49 term, 18 preterm) cases and 196 matched controls from first trimester plasma samples prospectively collected at King's College Hospital, London. Cell-free DNA was extracted and the four LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs were determined in BeWo trophoblast-like cells with luciferase assays.

RESULTS: A/C genotype in –98 position was the lowest in term PE compared to controls (p<0.032), similar to a South African cohort. Control but not all PE allele frequencies were in Hardy-Weinberg equilibrium (p=0.036). The Odds ratio for term PE calculated from prior risk, the A/A genotype and black ethnicity was 14 (p<0.001). In luciferase assays, the LGALS13 promoter “-98A" variant had 13% (p=0.04) and 26% (p<0.001) lower expression than the "-98C" variant in non-differentiated and differentiated BeWo cells, respectively. After 48-hour differentiation, there was 4.55- fold increase in expression of "-98C" variant versus 3.85-fold of "-98A" variant (p<0.001).

CONCLUSION: Lower LGALS13 (PP13) expression by the "-98A/A" genotype appears to impose higher risk to develop PE and could aid in PE prediction.

KeywordsPregnancy disorders; Placenta; PCR; Gene expression; Galectins; Single nucleotide polymorphism; LGALS13; Preeclampsia
Year2018
JournalFetal Diagnosis & Therapy
Journal citation43 (4), pp. 250-265
PublisherKarger
ISSN1015-3837
1421-9964
Digital Object Identifier (DOI)doi:10.1159/000477933
Official URLhttp://doi.org/10.1159/000477933
Publication dates
Online21 Jul 2017
PrintMay 2018
Publication process dates
Accepted30 May 2017
Deposited15 Jun 2020
Accepted author manuscript
Output statusPublished
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