Evidence map›Paper›PMID 41793551›Full record

ArticleMolecular biology reports2026

Functional characterization of the GWAS lead SNP rs888663 and effects of GDF15 SNPs on GDF15 levels in gestational hypertension and preeclampsia.

Daniela A Pereira, Julyane N S Kaihara, Luis Fernando P Passeti, João Locke F Araújo, Renan P Souza, Ana C Palei, Ricardo C Cavalli, Chengyu Deng, Nadav Ahituv, Valeria C Sandrim and 1 more

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Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Daniela A PereiraGraduate Program in Genetics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Julyane N S KaiharaDepartment of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Luis Fernando P PassetiDepartment of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
João Locke F AraújoGraduate Program in Genetics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Renan P SouzaDepartment of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Ana C PaleiDepartment of Surgery, University of Mississippi Medical Center, Jackson, MS, USA.
Ricardo C CavalliDepartment of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil.
Chengyu DengDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
Valeria C SandrimDepartment of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Marcelo R LuizonDepartment of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil. mrluizon@ufmg.br.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGrowth differentiation factor 15 (GDF15) is a biomarker for cardiovascular diseases, and its circulating levels are altered in preeclampsia (PE), which shares mechanisms with cardiovascular diseases. Several SNPs in the GDF15 locus were associated with GDF15 levels, including the GWAS lead SNP rs888663. However, no previous study had performed a functional characterization of rs888663 nor had tested the hypothesis that noncoding GDF15 SNPs affect GDF15 levels in PE or gestational hypertension (GH). We examined whether variation of rs888663 affects its enhancer activity, whether genotypes and haplotypes of rs888663 and rs1059369 are associated with PE or GH, and their effects on GDF15 levels in healthy pregnant (HP) women, and in patients with PE and GH. METHODS AND

resultsWe studied 233 HP women, 188 patients with PE, and 197 patients with GH. We performed a dual-luciferase reporter assay testing both rs888663 alleles (G/T), which found that the rs888663 region is a functional enhancer, and the T allele had a significantly higher enhancer activity. Genotypes were determined by Taqman allele discrimination assays. Plasma GDF15 levels were measured by ELISA. GDF15 levels were lower in PE and GH than in HP (P < 0.01). Patients with PE and GH carrying the TT genotype for rs1059369 and 'T, T' haplotype showed lower GDF15 levels than HP women carrying the same genotype and haplotype, respectively (P < 0.05).

conclusionOur findings identified a novel candidate enhancer of GDF15, with the rs888663 T allele leading to increased enhancer activity, and suggest that GDF15 SNPs affect GDF15 levels in PE or GH.

Indexed as

Bone Morphogenetic Protein 15Growth Differentiation Factor 15Hypertension, Pregnancy-InducedPre-EclampsiaAdultAllelesCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHaplotypesHumansPolymorphism, Single NucleotidePregnancyBone Morphogenetic Protein 15GDF15 protein, humanGrowth Differentiation Factor 15EnhancerGenetic polymorphismsGestational hypertensionGrowth differentiation factor 15 (GDF15)HaplotypesPreeclampsia

Identifiers

PMID41793551
PMCPMC12967388

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