Chorionic Gonadotropin β-Gene Variants Are Associated with Recurrent Miscarriage in Two European Populations

Context: The incidence of recurrent miscarriage (RM) (≥3 consecutive pregnancy losses) is estimated as 1–2% in fertile couples. Familial clustering of RM has suggested the contribution of a genetic component. Objective: A low level of human chorionic gonadotropin (HCG) in maternal serum during the first trimester of the pregnancy is a clinically accepted risk factor for miscarriage. We sought to study whether variation in chorionic gonadotropin β-subunit genes (CGBs) expressed in placenta may contribute to the risk of RM. Design: Resequencing of CGB5 and CGB8, the two most actively transcribed loci of the four HCG β-duplicate genes, was performed. Setting: A case-control study involving two sample sets, from Estonia (n = 194) and Finland (n = 185), was performed. Patients: RM patients (n = 184) and fertile controls (n = 195) participated in the study. Results: From 71 identified variants in CGB5 and CGB8, 48 polymorphisms were novel. Significant protective effect was associated with two single nucleotide ...