Relationship between HLA-DPA1 genetic polymorphism and anembryonic pregnancy

Human leukocyte antigen (HLA)-DP is an HLA class II molecule. Overexpression of HLA class II molecules in placental trophoblast cells may induce pregnancy loss. However, the association between HLA-DP and pregnancy loss remains unclear. HLA-DPA1 is an HLA-DP peptide chain. The objective of this study was to assess the association between HLA-DPA1 genetic polymorphism and anembryonic pregnancy, a type of early pregnancy loss, in the Chinese population.

A case-control study was designed to compare the frequencies of HLA-DPA1 gene polymorphisms in an anembryonic pregnancy group and a control group. Sixty-eight cases and 122 controls were recruited. Statistical analysis was performed to assess the correlation between single-nucleotide polymorphisms (SNPs) and anembryonic pregnancy susceptibility. MassARRAY high-throughput DNA analysis was used to analyze 19 HLA-DPA1 SNPs. To explore how HLA-DPA1 polymorphism could affect anembryonic pregnancy, HLA-DPA1 serum levels were analyzed by ELISA.

Homozygous typing of rs1431403 (CC and TT) significantly increased the risk of anembryonic pregnancy in the case group (OR_CC  = 3.13, 95% CI: 1.50-6.53; OR_TT  = 2.96, 95% CI: 1.31-6.66; OR_CC+TT  = 3.06, 95% CI: 1.62-5.78). In samples with high HLA-DPA1 levels (≥1,500 pg/ml), the homozygous rs1431403 genotypes (n_CC  = 21, 43.8%; n_TT  = 20, 57.1%) were observed more frequently than were heterozygous genotypes.

HLA-DPA1 rs1431403 may be a risk factor for anembryonic pregnancy in the Chinese population. Homozygous rs1431403 genotypes (CC and TT) may increase the risk of anembryonic pregnancy by aberrantly increasing the HLA-DPA1 levels.