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Several SNPs in the\n                      <jats:italic>GDF15<\/jats:italic>\n                      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\n                      <jats:italic>GDF15<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We 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 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01). Patients with PE and GH carrying the TT genotype for rs1059369 and \u2018T, T\u2019 haplotype showed lower GDF15 levels than HP women carrying the same genotype and haplotype, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings identified a novel candidate enhancer of\n                      <jats:italic>GDF15<\/jats:italic>\n                      , with the rs888663 T allele leading to increased enhancer activity, and suggest that\n                      <jats:italic>GDF15<\/jats:italic>\n                      SNPs affect GDF15 levels in PE or GH.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-11629-w","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T06:53:37Z","timestamp":1772866417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Functional characterization of the GWAS lead SNP rs888663 and effects of GDF15 SNPs on GDF15 levels in gestational hypertension and preeclampsia"],"prefix":"10.1007","volume":"53","author":[{"given":"Daniela A.","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julyane N. 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