title: Endothelial nitric oxide synthase gene variants and haplotypes associated with an increased risk of idiopathic recurrent miscarriage.
abstract: We investigated the association of endothelial nitric oxide synthase (NOS3) polymorphisms rs2070744 (-786T> C), 27-bp repeat 4b/4a, rs1799983 (Glu298Asp), rs3918188 (-734C> A), and rs743507 (113G> A) with idiopathic recurrent miscarriage (IRM). This was a case-control study involving women with confirmed IRM (n = 296), and 305 age- and ethnically matched control women. NOS3 rs2070744, rs1799983, rs3918188, and rs743507 genotyping was done by TaqMan assays; NOS3 4b/4a genotyping was done by PCR-ASA. A higher frequency of -786C and 298Asp alleles was seen in IRM cases, which remained associated independently with IRM on multivariate analysis. Allele and genotype distribution of 4b/4a, rs3918188 (-734C> A) and rs743507 (113A> G) were comparable between IRM cases and control women. Taking homozygous wild-type genotype as a reference, regression analysis confirmed the association of Glu298Asp and -786T/C, and rs743507 homozygous carriers with IRM risk. Marked linkage disequilibrium was seen between tested NOS3 variants, thus allowing the construction of 5-locus [-786T> C/4b4a/Glu298Asp/-734C> A/113G> A] haplotypes. Taking the common T4bGCA haplotype as a reference, multivariate analysis confirmed the positive association of C4bTCG haplotype with IRM, after controlling for traditional covariates. Genetic variation at the NOS3 locus represents a genetic risk factor for increased susceptibility to IRM.
authors.affiliation: College of Medicine and Medical Sciences, Arabian Gulf University , Manama , Bahrain.
authors.forename: W Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: B D
authors.initials: BD
authors.lastname: Guarino
authors.forename: M A
authors.initials: MA
authors.lastname: Al-Sulaiti
authors.forename: A S
authors.initials: AS
authors.lastname: Al-Busaidi
authors.forename: E
authors.initials: E
authors.lastname: Racoubian
authors.forename: R R
authors.initials: RR
authors.lastname: Finan
mesh_terms: D000026:Abortion, Habitual / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D018912:Arabs; D001445:Bahrain; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D009775:Obstetrics and Gynecology Department, Hospital; D010044:Outpatient Clinics, Hospital; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020080:Tandem Repeat Sequences
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III