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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, NG; Papp, Z; Romero, R; Nicolaides, KH; Meiri, H.
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 Diagn Ther. 2018; 43(4):250-265
Doi: 10.1159/000477933
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- Co-Autor*innen der Med Uni Graz
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Huppertz Berthold
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- Abstract:
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LGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance.
First-trimester plasma samples (49 term and 18 intermediate) of PE cases matched with 196 controls were collected from King's College Hospital, London, repository. Cell-free DNA was extracted and the LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs was determined in BeWo trophoblast-like cells with luciferase assays. Adjusted odds ratio (OR) was calculated for the A/A genotype combined with maternal risk factors.
The A/A, A/C, and C/C genotypes in the -98 promoter position were in Hardy-Weinberg equilibrium in the control but not in the PE group (p < 0.036). The dominant A/A genotype had higher frequency in the PE group (p < 0.001). The A/C and C/C genotypes protected from PE (p < 0.032). The ORs to develop term and all PE, calculated for the A/A genotype, previous PE, body mass index (BMI) >35, black ethnicity, and maternal age >40 were 15.6 and 11.0, respectively (p < 0.001). In luciferase assays, the "-98A" promoter variant had lower expression than the "-98C" variant in non-differentiated (-13%, p = 0.04) and differentiated (-26%, p < 0.001) BeWo cells. Forskolin-induced differentiation led to a larger expression increase in the "-98C" variant than in the "-98A" variant (4.55-fold vs. 3.85-fold, p < 0.001).
Lower LGALS13 (PP13) expression with the "A" nucleotide in the -98 promoter region position (compared to "C") and high OR calculated for the A/A genotype in the -98A/C promoter region position, history of previous PE, BMI >35, advanced maternal age >40, and black ethnicity could serve to aid in PE prediction in the first trimester.
© 2017 S. Karger AG, Basel.
- Find related publications in this database (using NLM MeSH Indexing)
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Adult -
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African Continental Ancestry Group -
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Female -
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Galectins - genetics
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Genetic Predisposition to Disease -
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Genotype -
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Humans -
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Maternal Age -
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Obesity - complications
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Polymorphism, Single Nucleotide -
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Pre-Eclampsia - etiology
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Pre-Eclampsia - genetics
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Pregnancy -
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Pregnancy Proteins - genetics
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Pregnancy Trimester, First - genetics
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Recurrence -
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Risk Factors -
- Find related publications in this database (Keywords)
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Pregnancy disorders
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Placenta
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PCR
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Gene expression
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Galectins
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Single nucleotide polymorphism
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LGALS13
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Preeclampsia