title: Co-stimulatory CD28 and transcription factor NFKB1 gene variants affect idiopathic recurrent miscarriages.
abstract: Co-stimulatory CD28 and transcription factor NFKB1 genes are considered as a crucial player in the determination of inflammatory responses; genetic variability in these may modulate the risk for idiopathic recurrent miscarriages (IRM). We investigated the association of functional variants of CD28 (rs3116496 T/C) and NFKB1 (rs28362491 ins/del and rs696 A/G) with IRM cases. We recruited 200 IRM women with a history of at least three consecutive pregnancy losses before 20th week of pregnancy and 300 fertile control women. Determination of CD28 (rs3116496 T/C) and NFKB1 (rs28362491 ins/del and rs696 A/G) gene variants were based on the polymerase chain reaction pursued by restriction fragment length polymorphism analysis and validated with Sanger sequencing. Single marker analysis and multifactor dimensionality reduction (MDR) model used to predict the IRM risk. We observed nearly three- to twofold increased risk in single marker analysis for minor homozygous genotypes of rs3116496 T/C, rs28362491 ins/del and rs696 A/G tag-SNPs in IRM cases, suggesting the risk association. In MDR analysis, we observed 10.5-fold augmented risk among IRM women in three-SNP model (rs3116496 T/C, rs28362491 ins/del and rs696 A/G). The eQTL mapping analyses was performed to strengthen the results of our study. The eQTL mapping analysis revealed that the variations in CD28 and NFKB1 gene content might affect the abundance of transcripts of CD28 and Family with sequence similarity 177 member A1 (FAM177A1) genes, respectively. These results suggest that CD28 and NFKB1 gene variants may be associated with increased risks to IRM.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Misra
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Bharti
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Computer Science and Engineering, Shri Ramswaroop Memorial University, Barabanki, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000483:Alleles; D018106:CD28 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D016017:Odds Ratio; D011247:Pregnancy; D040641:Quantitative Trait Loci; D055815:Young Adult
chemical_list: D018106:CD28 Antigens; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human