title: Interleukin-18 promoter polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population.
abstract: IL-18 is a pro-inflammatory cytokine that regulates the differentiation and effector functions of CD4+ (Th1) and CD8+ (CTL) T cells, which are implicated in the pathogenesis of recurrent pregnancy loss (RPL). We investigated the association of the IL-18 gene promoter single nucleotide polymorphisms (SNPs) -656C/A (rs1946519), -137G/C (rs187238), -119A/C (rs360718), and -105G/A (rs360717), by TaqMan assays in analysis in 470 Tunisian women comprising 235 RPL cases and 235 multi-parous controls. The association of IL-18 alleles, genotypes, and haplotypes with RPL was evaluated by Fisher's exact test and regression analysis. The frequency of minor alleles -105G/A (P<0.001) and -656C/A (P<0.001), but not -119A/C (P=0.93) or -137G/C (P=0.32), were higher in RPL cases. Significant differences were also noted in the genotype distribution of -105G/A (P<0.001) and -656C/A (P<0.001) between cases and controls. Four-locus (-656C/A, -137G/C, -119A/C, -105G/A) IL-18 haplotype analysis identified AGAA (corrected P<0.001), and CGAA (corrected P<0.001) haplotypes to be associated with increased RPL risk, after adjusting for age and BMI. These results demonstrate that -105G/A and -656C/A IL-18 variants are significantly associated with RPL.
authors.affiliation: Research Unit of Hematological and Autoimmune Diseases, University of Monastir, Monastir, Tunisia.
authors.forename: Safia
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Maryam
authors.initials: M
authors.lastname: Dandana
authors.forename: Kalthoum
authors.initials: K
authors.lastname: Magdoud
authors.forename: Sawssen
authors.initials: S
authors.lastname: Meddeb
authors.forename: Neila
authors.initials: N
authors.lastname: Ben Slama
authors.forename: Sondes
authors.initials: S
authors.lastname: Hizem
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
mesh_terms: D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D000328:Adult; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012306:Risk; D014416:Tunisia
chemical_list: D020382:Interleukin-18