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. https://doi.org/10.1159/000477933
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)https://doi.org/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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Akolekar, R., Panaitescu, A. M., Ciobanu, A., Syngelaki, A. and Nicolaides, K. H. 2019. Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 54, pp. 484-491. https://doi.org/10.1002/uog.20391
Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus
Minnella, G. P., Crupano, F. M., Syngelaki, A., Zidere, V., Akolekar, R. and Nicolaides, K. H. 2019. Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 637-644. https://doi.org/10.1002/uog.21956
Risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review of the literature
Beta, J., Lesmes-Heredia, C., Bedetti, C. and Akolekar, R. 2018. Risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review of the literature. Minerva Ginecologica. 70 (2), pp. 215-219. https://doi.org/10.23736/S0026-4784.17.04178-8
Fetal major cardiac defects and placental dysfunction at 11-13 weeks' gestation
Fantasia, I., Kasapoglu, D., Kasapoglu, T., Syngelaki, A., Akolekar, R. and Nicolaides, K. H. 2018. Fetal major cardiac defects and placental dysfunction at 11-13 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 51 (2), pp. 194-198. https://doi.org/10.1002/uog.18839
ASPRE trial: incidence of preterm pre-eclampsia in patients fulfilling ACOG and NICE criteria according to risk by FMF algorithm
Allen, A., Poon, L. C., Rolnik, D. L., Tan, M. Y., Delgado, J. L., Tsokaki, T., Akolekar, R., Singh, M., Andrade, W., Efeturk, T., Jani, J. C., Plasencia, W., Papaioannou, G., Blazquez, A. R., Carbone, I. F., Wright, D. and Nicolaides, K. H. 2018. ASPRE trial: incidence of preterm pre-eclampsia in patients fulfilling ACOG and NICE criteria according to risk by FMF algorithm. Ultrasound in Obstetrics and Gynecology. 51 (6), pp. 738-742. https://doi.org/10.1002/uog.19019
Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: results of SPREE
Tan, M. Y., Wright, D., Syngelaki, A., Akolekar, R., Cicero, S., Janga, D., Singh, M., Greco, E., Wright, A., Maclagan, K., Poon, L. C. and Nicolaides, K. H. 2018. Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: results of SPREE. Ultrasound in Obstetrics and Gynecology. 51 (6), pp. 743-750.
Ultrasonographic estimation of fetal weight: development of new model and assessment of performance of previous models
Hammami, A., Mazer Zumaeta, A., Syngelaki, A., Akolekar, R. and Nicolaides, K. H. 2018. Ultrasonographic estimation of fetal weight: development of new model and assessment of performance of previous models. Ultrasound in Obstetrics and Gynecology. 52 (1), pp. 35-43. https://doi.org/10.1002/uog.19066
Fetal Medicine Foundation fetal and neonatal population weight charts
Nicolaides, K. H., Wright, D., Syngelaki, A., Wright, A. and Akolekar, R. 2018. Fetal Medicine Foundation fetal and neonatal population weight charts. Ultrasound in Obstetrics and Gynecology. 52 (1), pp. 44-51. https://doi.org/10.1002/uog.19073
Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation
Tan, M.Y., Syngelaki, A., Poon, L.C., Rolnik, D.L., O'Gorman, N., Delgado, J.L., Akolekar, R., Konstantinidou, L., Tsavdaridou, M., Galeva, S., Ajdacka, U., Molina, F.S., Persico, N., Jani, J.C., Plasencia, W., Greco, E., Papaioannou, G., Wright, A., Wright, D. and Nicolaides, K.H. 2018. Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 52 (2), pp. 186-195. https://doi.org/10.1002/uog.19112
Reference ranges for the size of the fetal cardiac outflow tracts from 13 to 36 weeks gestation: a single-center study of over 7000 cases
Vigneswaran, T.V., Akolekar, R., Syngelaki, A., Charakida, M., Allan, L.D., Nicolaides, K.H., Zidere, V. and Simpson, J.M. 2018. Reference ranges for the size of the fetal cardiac outflow tracts from 13 to 36 weeks gestation: a single-center study of over 7000 cases. Circulation Cardiovascular Imaging. 11 (7), p. e007575. https://doi.org/10.1161/CIRCIMAGING.118.007575
Comparison of screening for pre-eclampsia at 31-34 weeks' gestation by sFlt-1/PlGF ratio and a method combining maternal factors with sFlt-1 and PlGF
Tan, M.Y., Wright, D., Koutoulas, L., Akolekar, R. and Nicolaides, K.H. 2017. Comparison of screening for pre-eclampsia at 31-34 weeks' gestation by sFlt-1/PlGF ratio and a method combining maternal factors with sFlt-1 and PlGF. Ultrasound in Obstetrics and Gynecology. 49 (2), pp. 201-208. https://doi.org/10.1002/uog.17307
Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 30-34 weeks' gestation
Wright, D., Dragan, I., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2017. Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 30-34 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 49 (2), pp. 194-200. https://doi.org/10.1002/uog.17309
Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation
O'Gorman, N., Wright, D., Poon, L.C., Rolnik, D.L., Syngelaki, A., Wright, A., Akolekar, R., Cicero, S., Janga, D., Jani, J., Molina, F.S., de Paco Matallana, C., Papantoniou, N., Persico, N., Plasencia, W., Singh, M. and Nicolaides, K.H. 2017. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 49 (6), pp. 751-755. https://doi.org/10.1002/uog.17399
Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 35-37 weeks' gestation
Panaitescu, A.M., Wright, D., Militello, A., Akolekar, R. and Nicolaides, K.H. 2017. Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 35-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 50 (3), pp. 383-387. https://doi.org/10.1002/uog.17419
Chronic hypertension and adverse pregnancy outcome: a cohort study
Panaitescu, A.M., Syngelaki, A., Prodan, N., Akolekar, R. and Nicolaides, K.H. 2017. Chronic hypertension and adverse pregnancy outcome: a cohort study. Ultrasound in Obstetrics and Gynecology. 50 (2), pp. 228-235. https://doi.org/10.1002/uog.17493
Impaired placentation in women with chronic hypertension who develop pre-eclampsia
Panaitescu, A.M., Akolekar, R., Kametas, N., Syngelaki, A. and Nicolaides, K.H. 2017. Impaired placentation in women with chronic hypertension who develop pre-eclampsia. Ultrasound in Obstetrics and Gynecology. 50 (4), pp. 496-500. https://doi.org/10.1002/uog.17517
Association of chronic hypertension with birth of small-for-gestational-age neonate
Panaitescu, A.M., Baschat, A.A., Akolekar, R., Syngelaki, A. and Nicolaides, K.H. 2017. Association of chronic hypertension with birth of small-for-gestational-age neonate. Ultrasound in Obstetrics and Gynecology. 50 (3), pp. 361-366. https://doi.org/10.1002/uog.17553
Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia
Rolnik, D.L., Wright, D., Poon, L.C., O'Gorman, N., Syngelaki, A., de Paco Matallana, C., Akolekar, R., Cicero, S., Janga, D., Singh, M., Molina, F.S., Persico, N., Jani, J.C., Plasencia, W., Papaioannou, G., Tenenbaum-Gavish, K., Meiri, H., Gizurarson, S., Maclagan, K. and Nicolaides, K.H. 2017. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. The New England Journal of Medicine. 377 (7), pp. 613-622. https://doi.org/10.1056/NEJMoa1704559
Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.
Poon, L.C., Wright, D., Rolnik, D.L., Syngelaki, A., Delgado, J.L., Tsokaki, T., Leipold, G., Akolekar, R., Shearing, S., De Stefani, L., Jani, J.C., Plasencia, W., Evangelinakis, N., Gonzalez-Vanegas, O., Persico, N., Nicolaides, K.H. and Allen, A. 2017. Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history. American Journal of Obstetrics & Gynecology. 217 (5), pp. 585.e1- 5.. https://doi.org/10.1016/j.ajog.2017.07.038
Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin
Balani, J., Hyer, S., Syngelaki, A., Akolekar, R., Nicolaides, K. H., Johnson, A. and Shehata, H. 2017. Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin. Obstetric Medicine. 10, pp. 170-173. https://doi.org/10.1177/1753495X17725465
Metformin versus placebo in obese pregnant women without diabetes mellitus
Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., Pastides, A. and Shehata, H. 2016. Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine. 374, pp. 434-43. https://doi.org/10.1056/NEJMoa1509819
Prediction of stillbirth from maternal demographic and pregnancy characteristics
Yerlikaya, G., Akolekar, R., McPherson, K., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal demographic and pregnancy characteristics. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 607-612. https://doi.org/10.1002/uog.17290
Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks
Akolekar, R., Tokunaka, M., Ortega, N., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 624-630. https://doi.org/10.1002/uog.17295