title: 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.
abstract: 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.
authors.affiliation: Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Rohini R
authors.initials: RR
authors.lastname: Nair
authors.forename: Anuradha
authors.initials: A
authors.lastname: Khanna
authors.forename: Kiran
authors.initials: K
authors.lastname: Singh
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D016923:Cell Death; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk; D015398:Signal Transduction; D019014:fas Receptor / Q000235:genetics*
chemical_list: D019014:fas Receptor