Abstract
To investigate possible associations of P-selectin polymorphisms with idiopathic recurrent pregnancy loss (RPL).
Study subjects comprised 270 consecutive RPL cases attending outpatient maternity services, and 322 multi-parous control women. P-selectin genotyping was done by PCR-RFLP and PCR-ASA methods.
The P-selectin variants rs1800807, rs1800805, and rs6127, were in Hardy Weinberg equilibrium, and low linkage disequilibrium was noted between the three studied SNPs. The frequency of rs6127 A allele (P<0.001I), but not rs1800807 C allele (P=0.957) or rs1800805 A allele (P=0.760), was higher in RPL cases than in control women. Significant differences in the distribution of rs6127 (P<0.001), but not rs1800807 (P=0.444) or rs1800805 (P=0.391) genotypes were seen between cases and controls, and only rs6127 showed a significant association with RPL, with increments of 2.65 and 4.96 in disease risk seen for heterozygous and homozygous carriers, respectively. Among the 8 three-locus Pselectin haplotypes constructed (rs1800807/rs1800805/rs6127), increased frequency of GGG (Pc=0.0249), CGG (Pc=0.0256), and CAG (Pc=0.0174) haplotypes, and lower frequency of CGA haplotype (Pc=0.0091) were seen in RPL cases, thus conferring disease susceptibility and protective nature to these haplotypes, respectively.
P-selectin gene polymorphisms and haplotypes contribute to RPL development.
► SELP variants and haplotypes increase the risk of recurrent pregnancy loss (RPL). ► SELP N562D/C-2123G (rs6127) polymorphism was significantly associated with RPL. ► RPL risk of 2.65 and 4.96 in seen for heterozygous and homozygous rs6127 carriers. ► RPL-susceptible (GGG, CGG, CAG) and -protective (CGA) SELP haplotypes were seen.