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.

Abstract

BACKGROUND:

LGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Liora Madar-Shapiro, Ido Karady, Alla Trahtenherts, Argryo Syngelaki, Ranjit Akolekar, Liona Poon, Ruth Cohen, Adi Sharabi-Nov, Berthold Huppertz, Marei Sammar, Kata Juhasz, Nandor Gabor Than, Zoltan Papp, Roberto Romero, Kypros H Nicolaides, Hamutal Meiri
• Journal: Fetal diagnosis and therapy (Fetal Diagn Ther) Vol. 43 Issue 4 Pg. 250-265 ( 2018) ISSN: 1421-9964 [Electronic] Switzerland
• PMID: 28728156 (Publication Type: Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Galectins
• LGALS13 protein, human
• Pregnancy Proteins

Topics

• Adult
• Black People
• Female
• Galectins (genetics)
• Genetic Predisposition to Disease
• Genotype
• Humans
• Maternal Age
• Obesity (complications)
• Polymorphism, Single Nucleotide
• Pre-Eclampsia (etiology, genetics)
• Pregnancy
• Pregnancy Proteins (genetics)
• Pregnancy Trimester, First (genetics)
• Recurrence
• Risk Factors