Association of FAS −1377 G>A and FAS −670 A>G functional polymorphisms of FAS gene of cell death pathway with recurrent early pregnancy loss risk

Apoptosis during the early stages of pregnancy enables the remodeling of the uterus for proper placentation. Apoptosis in the maternal activated cytotoxic T lymphocytes allows maternal immune tolerance to pregnancy and in glandular and stromal cells it helps with trophoblastic endometrial invasion. FAS gene is expressed at the maternal–fetal interface and is involved in the regulation of immune response and implantation. Altered FAS expression may result in altered apoptosis and ultimately affects both immune response and implantation. FAS −1377 G>A and FAS −670 A>G functional polymorphisms in the promoter region of FAS gene modulate its expression at transcriptional level. In a case–control study the contribution of FAS −1377 G>A and FAS −670 A>G polymorphisms to the risk of recurrent early pregnancy loss (REPL) was evaluated. DNA from 134 cases with a history of three or more REPL and 124 healthy controls with successful pregnancy outcomes were genotyped through PCR-RFLP. DNA sequencing was used to ascertain PCR-RFLP results. The genotype and allele frequencies for FAS −1377 G>A and FAS −670 A>G polymorphisms were compared in REPL and controls. FAS −1377 AA and AG genotypes were associated with an increased risk of REPL (OR, 3.25; 95%CI, 1.52–6.98 and OR, 2.62; 95%CI, 1.48–4.64, respectively), whereas FAS −670 genotypes conferred no risk. The −1377 AA/−670 GG genotypes combination of FAS polymorphisms showed highest risk (OR, 8.15; 95%CI, 2.75–25.81). Genotype combinations −1377 GA/−670 AA and −1377 GA/−670 AG were also statistically significant, suggestive of their role in REPL risk.