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. Epub 2017 Jul 21.


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.

Keywords: LGALS13; Galectins; Gene expression; PCR; Placenta; Preeclampsia; Pregnancy disorders; Single nucleotide polymorphism.

MeSH terms

  • Adult
  • African Continental Ancestry Group*
  • Female
  • Galectins / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Maternal Age*
  • Obesity / complications*
  • Polymorphism, Single Nucleotide*
  • Pre-Eclampsia / etiology*
  • Pre-Eclampsia / genetics
  • Pregnancy
  • Pregnancy Proteins / genetics*
  • Pregnancy Trimester, First / genetics*
  • Recurrence
  • Risk Factors


  • Galectins
  • LGALS13 protein, human
  • Pregnancy Proteins