HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent 1

摘要: Background: HLA-G is a nonclassical, class I major histocompatibility complex (MHC) gene 25 that is constitutively expressed on placental cytotrophoblasts at the maternal-fetal interface, and 26 likely plays a role in the maintenance of successful pregnancy. In this study, we investigated the 27 role of HLA-G polymorphisms on risk for recurrent pregnancy loss (RPL) and on circulating 28 levels of soluble (s) HLA-G in Iraqi women. 29Methods: Blood samples were collected at 9 to 12 weeks gestation from 50 women with RPL 30 and 50 healthy pregnant women seeking medical care in Basrah province, Iraq. DNA from these 31 subjects was genotyped for six HLA-G polymorphisms that define eight of the most common 32 alleles (or haplotypes). sHLA-G was measured in plasma collected in the first trimester of 33 pregnancy. 34Results: Median sHLA-G levels were significantly lower in the RPL cases compared to healthy 35 controls (21.4 vs. 38.8 U/ml, respectively; P= 0.025), and decreased with increased maternal age 36 (P= 0.0051). However, the frequencies of alleles at the six polymorphic sites or of the seven 37 HLA-G haplotypes did not differ significantly between cases and controls (P≥ 0.15 and 0.15, 38 respectively). In contrast, homozygosity for the C allele (CC) at a tri-allelic promoter 39 polymorphism,-725C/G/T, was associated with lower concentrations of sHLA-G compared to 40 women with the CG or CT genotypes (median levels 21.1 vs. 40.1 vs. 42.6 U/ml, respectively; P 41= 0.0089). Genotype effects on sHLA-G levels were present in both the RPL cases and healthy 42 controls, and were independent of maternal age. 43 …