{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T06:01:30Z","timestamp":1763618490078,"version":"3.45.0"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"crossref","award":["262700"],"award-info":[{"award-number":["262700"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Child Health and Human Development","award":["R21 HD046624-02"],"award-info":[{"award-number":["R21 HD046624-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Serine protease inhibitor A3 (SERPINA3), also called \u03b1-1-antichymotrypsin, is a serine protease involved in placental dysfunction. This study examines SERPINA3 polymorphisms and haplotypes for associations with maternal hypertensive disorders of pregnancy (HDPs) and preeclampsia with severe features (sPE) or Hemolysis, Elevated Liver Enzymes, and Low Platelet (HELLP) syndrome in mother\u2013baby dyads (HDP) and mother\u2013father\u2013baby triads (sPE\/HELLP). This retrospective case\u2013control study examined two patient cohorts, HDPs and severe PE\/HELLP syndrome. The HDP population included cases (n = 142) and controls (n = 168) of mother\u2013baby dyads recruited from a large, urban, safety-net hospital in Los Angeles. The sPE\/HELLP syndrome population included cases (n = 189) and controls (n = 28) of mother\u2013father\u2013baby triads recruited through HELLP syndrome research websites. Cases were verified by medical chart abstraction when possible. Two SERPINA3 SNPs, rs4934 and rs1884082, were genotyped from saliva samples, mouthwash, or buccal swabs. The Haplin package in R was used to perform genetic association analyses. No evidence of increased risk related to individual SERPINA3 SNPs or haplotypes for the developing HDPs or sPE\/HELLP was found in individual nor combined cohorts. In the HDP cohort, the g-a haplotype (relative to T-G haplotype) was borderline significant for increased risk of HDPs when carried by the child (double dose: RR = 1.58, 95% CI: (1.00, 2.52), p = 0.05). We observed significant parent-of-origin (PoO) effects in the combined cohort: specifically, an increased risk of HDPs\/sPE\/HELLP if the mother carries a double copy for both rs4934 (RR = 3.03, 95% CI (1.50, 6.09), p &lt; 0.01) and rs1884082 (RR = 2.38, 95% CI (1.22, 4.71), p = 0.01). A reduced risk of HDPs\/sPE\/HELLP was observed for rs4934 (RR = 0.54, 95% CI (0.31, 0.98), p = 0.04) and rs1884082 (RR = 0.52, 95% CI (0.30, 0.91), p = 0.02) with child carriage of the maternally inherited allele. In contrast, child carriage of a paternally inherited copy of the variant allele for rs4934 increased risk of HDPs\/sPE\/HELLP (RR = 1.54, 95% CI (1.09, 2.20), p = 0.02). There was no evidence that SERPINA3 gene polymorphisms and haplotypes were associated with risk of HDPs or sPE\/HELLP. However, significant PoO effects were observed in the combined cohort analysis, with child carriage of rs4934 that is maternally inherited decreasing HDPs\/sPE\/HELLP risk while a paternally inherited copy increases risk, suggesting a role for maternal\u2013fetal genomic incompatibility.<\/jats:p>","DOI":"10.3390\/cimb47110952","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:03:15Z","timestamp":1763564595000},"page":"952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal and Fetal SERPINA3 Polymorphisms and Risk of Preeclampsia: A Dyad and Triad Based Case-Control Study"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5909-6395","authenticated-orcid":false,"given":"Hsi-Hsuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California,  Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-1476","authenticated-orcid":false,"given":"Claire","family":"Baldauf","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-641X","authenticated-orcid":false,"given":"Trevor A.","family":"Pickering","sequence":"additional","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California,  Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-1063","authenticated-orcid":false,"given":"H\u00e5kon K.","family":"Gjessing","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health, 0379 Oslo, Norway"},{"name":"Department of Global Public Health and Primary Care, University of Bergen, 5009 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-8745","authenticated-orcid":false,"given":"Sue Ann","family":"Ingles","sequence":"additional","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California,  Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7785-4221","authenticated-orcid":false,"given":"Melissa Lee","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California,  Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy (2000). 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