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The clearance of placenta\u2010derived material is one of the functions of the complement system in pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>We genotyped 500 women with pre\u2010eclamptic pregnancies and 190 pregnant women without pre\u2010eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre\u2010eclamptic pregnancies and 1905 controls from the national FINRISK cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS\u20101 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>Allele frequencies were compared between pre\u2010eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The most significantly pre\u2010eclampsia\u2010linked CR3 variant M441K (<jats:italic>P<\/jats:italic>\u00a0=\u00a04.27E\u20104, OR\u00a0=\u00a01.401, 95%\u00a0CI\u00a0=\u00a01.167\u20131.682) displayed a trend of increased adhesion to iC3b (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Results suggest that changes in complement\u2010facilitated phagocytosis are associated with pre\u2010eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro\u2010 and anti\u2010inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre\u2010eclampsia pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable abstract<\/jats:title><jats:p>Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre\u2010eclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.16660","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T01:11:08Z","timestamp":1612746668000},"page":"1282-1291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dysfunction of complement receptors CR3 (CD11b\/18) and CR4 (CD11c\/18) in pre\u2010eclampsia: a genetic and functional 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Rheumatology Washington University School of Medicine Saint Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Daly","sequence":"additional","affiliation":[{"name":"Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Herantis Pharma Plc Espoo Finland"},{"name":"Neuroscience Center HiLife University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Uotila","sequence":"additional","affiliation":[{"name":"Research Services University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Llort Asens","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Biosciences Research Program Faculty of Bio\u2010 and Environmental Sciences University of Helsinki Helsinki 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