title: Protein Z variants associated with protein Z plasma levels and with risk of idiopathic recurrent miscarriage.
abstract: Protein Z (PZ) deficiency due to anti-PZ autoantibodies and/or mutations in PZgene was linked with adverse pregnancy outcomes, including idiopathic recurrent miscarriage (IRM). We investigated the association of rs3024718, rs3024719, rs3024731, rs3024778, rs3024772, and rs3024735 (G79A) PZ variants and changes in PZ levels in 287 women with IRM, and 308 control women. Of the 6 single nucleotide polymorphisms (SNPs) analyzed, higher minor allele frequency of rs3024735 (G79A) and rs3024731 were seen in IRM cases than in control women. Significantly higher frequencies of rs3024735/G79A G/A and A/A (P< .001), rs3024719 G/A (P= .009), and rs3024731 A/A (P = .012), but not rs3024718 (P= .12), rs3024778 (P = .76), or rs3024772 (P= .27) genotype carriers were seen between IRM cases versus control women, respectively, and was linked with reduced PZ levels. Six-locus (rs3024718/rs3024719/rs3024778/rs3024731/rs3024735/rs3024772) PZhaplotypes analysis demonstrated increased frequency of GAGAAG and AGGTAG and reduced frequency of AGGTGC haplotypes in IRM cases, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. These results demonstrate that specific PZSNPs and haplotypes are significantly associated with IRM.
authors: Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
authors: Fatima S
authors: FS
authors: Al-Shaikh
authors: Mai S
authors: MS
authors: Sater
authors: Ramzi R
authors: RR
authors: Finan
authors: Eddie
authors: E
authors: Racoubian
authors: Tala M
authors: TM
authors: Abu-Hijleh
authors: Fekria E
authors: FE
authors: Mustafa
authors: Wassim Y
authors: WY
authors: Almawi
mesh_terms: D000026:Abortion, Habitual / Q000097:blood* / Q000235:genetics*; D000328:Adult; D001798:Blood Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001798:Blood Proteins; C026080:plasma protein Z
keywords: haplotypes; idiopathic recurrent miscarriage; protein Z