Polymorphisms in genes coding for the NK-cell receptor NKG2D and its ligand MICA in recurrent miscarriage

Problem: To investigate the possible association of Natural Killer Group (NKG) receptors gene polymorphisms and MHC class I chain-related protein A (MICA) gene polymorphism with recurrent miscarriage (RM).

Methods: Seven SNPs in NKG2D gene (rs1049174, rs2255336, rs2617160, rs2617161, rs2246809, rs2617169, and rs2617170), one SNP in NKG2A gene (rs1983526), and one SNP in MICA gene (MICA129) were assessed by allelic discrimination (real-time PCR) in both patients and control women.

Results: The rs2617170 T/T genotype significantly protected against RM [OR (95%) = 0.63 (0.40-0.98)]. The NKG2D haplotypes analysis on the basis of pairwise LD revealed two haplotype blocks. In block1, we found an increased frequency of CAT (Pc = 0.007; OR = 2.13; 95% CI = 1.24-3.68) and GGA haplotypes (Pc = 0.041; OR = 2.02; 95%CI = 1.03-3.96) and reduced frequency of CAA haplotype (Pc = 0.027; OR = 0.72; 95% CI = 0.54-0.96) in patients. In block2, increased frequency of GATG haplotype (Pc = 10(-4) ; OR = 9.25; 95% CI = 3.04-28.12) and reduced frequency of ATTC haplotype (Pc = 0.035; OR = 0.69; 95%CI = 0.50-0.97) were seen in patients.

Conclusion: The NKG2D gene polymorphisms may influence the success of pregnancy in Tunisian women.