Association Study of Hyaluronan-Binding Protein 2 (HABP2) Gene Polymorphisms in Idiopathic Recurrent Pregnancy Loss (RPL) in Korean Women

Recurrent pregnancy loss (RPL), also termed recurrent spontaneous abortion, is defined as the failure of ≥2 consecutive pregnancies before 20 weeks of gestation. Approximately 5% of pregnant couples experience RPL. The hyaluronan-binding protein 2 (<i>HABP2</i>) gene is involved in coagulation and plays an important role during pregnancy. In >50% of RPLs, the etiology remains unexplained. We collected 765 blood samples from 388 female RPL patients and 377 healthy female controls. To investigate the relationships between <i>HABP2</i> polymorphisms and RPL, we examined six <i>HABP2</i> variants (rs3832698 A>del, rs10885478 G>A, rs932650 T>C, rs7923349 G>T, rs1157916 G>A, and rs2240879 T>C) to clarify their association with RPL risk. The rs2240879 CC genotype was significantly associated with an increased RPL risk (<i>p</i> = 0.028). In haplotype analysis, the combination of rs3832698 del and rs2240879 T (del-T) was associated with elevated risk (<i>p</i> = 0.043); this risk persisted in combinations with additional polymorphisms (rs3832698 A>del, rs10885478 G>A, rs932650 T>C, rs7923349 G>T; del-A-T-T, <i>p</i> < 0.001; rs3832698 A>del, rs10885478 G>A, rs932650 T>C, rs7923349 G>T, rs1157916 G>A, rs2240879 T>C; del-A-C-T-G-T, <i>p</i> = 0.024). The rs3832698 and rs1157916 genotypes were significantly associated with prothrombin time (<i>p</i> = 0.020 and <i>p</i> = 0.012, respectively). We identified associations between <i>HABP2</i> polymorphisms and RPL; rs2240879 was linked to an increased RPL risk. Additionally, rs3832698 was associated with an altered prothrombin time. These findings suggest that <i>HABP2</i> represents a biomarker for RPL susceptibility.