Association of HLA-G 3′UTR gene polymorphism with the risk of unexplained spontaneous recurrent abortion / 中华检验医学杂志

ABSTRACT

Objective:To investigate the distribution of single nucleotide polymorphism and haplotype of human leucocyte antigen G 3′untranslated region gene, which possibly could be predictive roles in unexplained recurrent spontaneous abortion patients.Methods:Case-control method was used in this study. 70 cases of pregnant women with unexplained recurrent spontaneous abortion and 54 cases of prenatal examination women whose peripheral blood and serum were collected in Wenzhou Hospital of Chinese Traditional Medicine were recorded from June 2017 to July 2018. Blood gene DNA was extracted by centrifuge column and was amplified by polymerase chain reaction. Sanger sequencing method was used for genotyping. The genotypes frequency, linkage imbalance analysis and haplotypes construction of SNPs were analyzed by SHEsis online software and Phase software. Serum soluble HLA-G concentration was detected by ELISA.Results:There were eight SNPs, including 14bp ins/del,+3003C/T,+3010G/C,+3027A/C,+3035C/T,+3142C/G,+3187A/G and+3196C/G, were detected in both the URSA group and the control group. Results showed that the distribution differences of+3010G/C,+3142C/G and+3187A/G between the two groups were statistically significant (χ 2=8.514, P=0.004; χ 2=0.552, P=0.021; χ 2=8.183, P=0.005) .The C allele at the+3010G/C site and the G allele at the +3142C/G site might be risk factors for URSA ( OR=2.131, 95 %CI=1.278-3.552, χ 2=8.514, P=0.004; OR=1.813, 95 %CI=1.091-3.013, χ 2=0.552, P=0.021) ;the G allele at +3187A/G site might be a protective factor for URSA ( OR=0.476, 95 %CI=0.285-0.794, χ 2=8.183, P=0.005) .Haplotype analysis revealed that UTR-1 (DTGCCCGC) might be a protective factor for URSA ( OR=0.497, 95 %CI=0.295-0.837,χ 2=6.987, P=0.008), while UTR-3 (DTCCCGAC) might be a risk factor for URSA ( OR=1.732, 95 %CI=1.009-2.974, χ 2=3.998, P=0.045).The frequency of UTR-1/UTR-1 homozygous in URSA patients was lower than that in normal patients obviously( OR=0.381, 95 %CI=0.165-0.879, χ 2=5.292, P=0.024), which might be a protective factor for pregnancy. No association was found between serum soluble HLA-G and HLA-G 3′UTR gene haplotypes in URSA ( t=1.578, P=0.119) . Conclusions:HLA-G 3′UTR gene polymorphism and haplotypes are correlated with URSA. The study lays a foundation for future research and provides a basis for clinical individualized medicine.