Rare variants in genes coding for components of the terminal pathway of the complement system in preeclampsia

Abstract Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of the complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study 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 terminal complement pathway predispose to preeclampsia.