TY - JOUR
T1 - Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia
AU - The FINNPEC Core Investigator Group
AU - Lokki, A. Inkeri
AU - Triebwasser, Michael
AU - Daly, Emma
AU - Pouta, Anneli
AU - Kivinen, Katja
AU - Kere, Juha
AU - Kajantie, Eero
AU - Heinonen, Seppo
AU - Kurki, Mitja I.
AU - Perola, Markus
AU - Auro, Kirsi
AU - Salmon, Jane E.
AU - Anuja, Java
AU - Daly, Mark
AU - Atkinson, John P.
AU - Laivuori, Hannele
AU - Meri, Seppo
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25–467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17–440.78), p value = 0.01). In addition, one predisposing rare variant and one protective rare variant were discovered in C6 (rs41271067: D396G, OR (CI95) = 2.93 (1.18–7.10), p value = 0.01 and rs114609505: T190I, 0.02 OR (CI95) = 0.47 (0.22–0.92), p value = 0.02). The results suggest that variants in the terminal complement pathway predispose to preeclampsia.
AB - Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25–467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17–440.78), p value = 0.01). In addition, one predisposing rare variant and one protective rare variant were discovered in C6 (rs41271067: D396G, OR (CI95) = 2.93 (1.18–7.10), p value = 0.01 and rs114609505: T190I, 0.02 OR (CI95) = 0.47 (0.22–0.92), p value = 0.02). The results suggest that variants in the terminal complement pathway predispose to preeclampsia.
UR - http://www.scopus.com/inward/record.url?scp=85212705635&partnerID=8YFLogxK
U2 - 10.1038/s41435-024-00310-6
DO - 10.1038/s41435-024-00310-6
M3 - Article
C2 - 39690307
AN - SCOPUS:85212705635
SN - 1466-4879
JO - Genes and Immunity
JF - Genes and Immunity
M1 - 101337
ER -