Novel Association of Thrombophilic PROS1, PROC and CPB2 Genes Polymorphisms with Recurrent Spontaneous Miscarriage Women in Jordan

Abstract

Recurrent spontaneous miscarriage (RSM) is a gynecological complication has multifactorial etiologies including genetic factors. However, role of thrombophilic gene polymorphisms in RSA among Jordanian women is limited. This study explores the association between polymorphisms in SERPINC1, PROC, PROS1, PROZ, F5, F13A1, and CPB2 and RSA risk in Jordanian pregnant women. Blood samples were taken from 188 women with recurrent spontaneous miscarriage (RSM) and 193 control subjects without a history of miscarriage. Genomic DNA was extracted and analyzed for polymorphisms of thrombophilic genes using Kompetitive Allele Specific Polymerase Chain Reaction. The SNPStats tool was used to assess haplotype, genotype, and allele frequencies, with chi-square (χ²) tests employed to evaluate statistical significance. A total of seven thrombophilic genes were analyzed. The rs8178607 polymorphism in PROS1 was significantly associated with RSA in Jordanian women under the allelic (OR = 2.06, p = .014), codominant (OR = 2.05, p = .021), dominant (OR = 1.27, p = .015), and overdominant (OR = 1.91, p = .03) genetic models. Additionally, significant associations in the recessive model were observed for the rs1799810 and the rs1926447 polymorphisms in PROC (OR = 1.66, p = .038) and in CPB2 (OR = 1.89, p = .046), respectively. Our data preliminary demonstrates that the rs8178607, rs1799810, and rs1926447 genotypes of PROS1, PROC, and CPB2 respectively, are associated with an increased risk of RSA among Jordanian pregnant women. Further investigations with larger cohorts and family-based analyses are essential to elucidate the genetic variation of biochemical pathways and mechanisms influences recurrent miscarriage susceptibility.

Keywords: CPB2; PROC; PROS1; recurrent spontaneous miscarriage; single- nucleotide polymorphism.