Safia Messaoudi

Publications (6)9.99 Total impact

• Article: Contribution of JAK2 and STAT3 Variants to the Genetic Susceptibility of Recurrent Spontaneous Miscarriage in a Tunisian Population.

  Safia Messaoudi, Sondes Hizem, Manar A Al-Sulaiti, Amna S Al-Busaidi, Kalthoum Magdoud, Maryam Dendana, Wassim Y Almawi, Touhami Mahjoub
  [show abstract] [hide abstract]
  ABSTRACT: Aims: Th1 and Th2 balance is crucial for maintenance of pregnancy, and intracellular JAK and STAT proteins significantly contribute to it. In view of evidence linking JAK2 and STAT3 variants with recurrent spontaneous miscarriage (RSM), here we investigated the association of JAK2 (rs2230724) and STAT3 (rs1053023 and rs1053004) to RSM susceptibility in Tunisians. Subjects and Methods: A retrospective case-control study. Subjects comprised 235 RSM cases and 235 control subjects. JAK2 and STAT3 were genotyped by the allelic discrimination method. Results: STAT3 rs1053023 and, to a lower extent, rs1053004 were significantly associated with RSM under the additive and dominant, but not recessive models. This remained significant after adjustment for the covariates age, smoking, and gravida. In contrast to STAT3 variants, JAK2 rs2230724 was not associated with RSM under any of the genetic models tested. Two-locus STAT3 (rs1053023/rs1053004) haplotype analysis revealed increased frequency of the C/G haplotype in patients with RSM. Multivariate regression analysis confirmed the association of C/G haplotype with RSM (p=0.001; odds ratio=2.01; 95% confidence interval=1.32-3.07), thus conferring RSM susceptibility nature. These differences remained significant after applying the Bonferroni correction for multiple testing (Pc=0.004). Conclusions: STAT3 rs1053023, more so than the STAT3 rs1053004 or JAK2 rs2230724 polymorphisms, is associated with RSM risk.
  Genetic Testing and Molecular Biomarkers 11/2012; · 1.11 Impact Factor
• Article: Interleukin-18 promoter polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population.

  Safia Messaoudi, Maryam Dandana, Kalthoum Magdoud, Sawssen Meddeb, Neila Ben Slama, Sondes Hizem, Touhami Mahjoub
  [show abstract] [hide abstract]
  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.
  Journal of Reproductive Immunology 03/2012; 93(2):109-13. · 2.97 Impact Factor
• Article: Endothelial protein C receptor 1651C/G polymorphism and soluble endothelial protein C receptor levels in women with idiopathic recurrent miscarriage.

  Maryam Dendana, Safia Messaoudi, Sondes Hizem, Khaled B Jazia, Wassim Y Almawi, Jean-Christophe Gris, Touhami Mahjoub
  [show abstract] [hide abstract]
  ABSTRACT: High levels of soluble endothelial protein C receptor (EPCR) induce coagulation dysfunction by inhibiting protein C activation, and activated protein C (APC) activity. We tested whether EPCR 1651C/G promoter variant and changes in plasma soluble EPCR levels are risk factors for idiopathic recurrent spontaneous miscarriage (RSM). A case-control study involving 283 RSM cases and 380 age and BMI-matched control women. EPCR 1651C/G genotyping was performed by PCR-RFLP method. Plasma-soluble EPCR levels were measured with ELISA. The 1651G allele frequency and C/G genotype were significantly higher in RSM cases than controls; none of the cases or control participants was a 1651G/G homozygote. Lower soluble EPCR levels were seen in RSM cases compared to controls, and higher soluble EPCR levels were seen in 1651C/G compared to 1651C/C carriers in cases and controls. Lower soluble EPCR levels were seen in cases, both in 1651C/C (P = 0.0046) and 1651C/G (P = 0.0032) genotype carriers. Multivariate analysis demonstrated strong association of EPCR 1651C/G [P = 0.011; adjusted odds ratio (aOR) (95% confidence interval [CI] = 3.13 (1.31-7.60)], but not soluble EPCR plasma levels [P = 0.067; aOR (95% CI) = 1.01 (1.00-1.10)], with increased RSM risk. In addition, smoking was independently associated with increased RSM risk [P = 0.002; aOR (95% CI) = 2.86 (1.48-5.52)]. EPCR 1651C/G polymorphism and elevated soluble EPCR levels but low soluble EPCR levels increase the risk of idiopathic RSM. Replication studies on other racial groups, and other EPCR gene variants, are warranted.
  Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 01/2012; 23(1):30-4. · 1.25 Impact Factor
• Article: Common polymorphisms in the P-selectin gene in women with recurrent spontaneous abortions.

  Maryam Dendana, Sondes Hizem, Kalthoum Magddoud, Safia Messaoudi, Walid Zammiti, Mona Nouira, Wassim Youssef Almawi, Touhami Mahjoub
  [show abstract] [hide abstract]
  ABSTRACT: To investigate possible associations of P-selectin polymorphisms with idiopathic recurrent pregnancy loss (RPL). Study subjects comprised 270 consecutive RPL cases attending outpatient maternity services, and 322 multi-parous control women. P-selectin genotyping was done by PCR-RFLP and PCR-ASA methods. The P-selectin variants rs1800807, rs1800805, and rs6127, were in Hardy Weinberg equilibrium, and low linkage disequilibrium was noted between the three studied SNPs. The frequency of rs6127 A allele (P<0.001I), but not rs1800807 C allele (P=0.957) or rs1800805 A allele (P=0.760), was higher in RPL cases than in control women. Significant differences in the distribution of rs6127 (P<0.001), but not rs1800807 (P=0.444) or rs1800805 (P=0.391) genotypes were seen between cases and controls, and only rs6127 showed a significant association with RPL, with increments of 2.65 and 4.96 in disease risk seen for heterozygous and homozygous carriers, respectively. Among the 8 three-locus Pselectin haplotypes constructed (rs1800807/rs1800805/rs6127), increased frequency of GGG (Pc=0.0249), CGG (Pc=0.0256), and CAG (Pc=0.0174) haplotypes, and lower frequency of CGA haplotype (Pc=0.0091) were seen in RPL cases, thus conferring disease susceptibility and protective nature to these haplotypes, respectively. P-selectin gene polymorphisms and haplotypes contribute to RPL development.
  Gene 12/2011; 495(1):72-5. · 2.34 Impact Factor
• Article: Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage.

  Safia Messaoudi, Ghada M Al-Khateeb, Maryam Dendana, Mai S Sater, Khaled B Jazia, Mounia Nouira, Wassim Y Almawi, Touhami Mahjoub
  [show abstract] [hide abstract]
  ABSTRACT: Insofar as recurrent spontaneous miscarriage (RSM) is linked with dysregulated immunity and inflammatory changes, and given the pro-inflammatory role of interleukin-21 (IL-21), we examined the association between IL-21 polymorphisms and RSM. IL-21 rs2055979, rs13143866, rs9992580, and rs4833837 were genotyped in 235 cases of RSM and 235 controls. Regression analysis was employed in assessing the contribution of IL-21 variants to the overall RSM risk. Higher minor allele and genotype frequencies of rs2055979 and rs13143866, but not rs9992580 or rs4833837, were seen in RSM patients than in the controls. IL-21 haplotype [rs9992580/rs4833837/rs2055979/rs13143866] analysis revealed a lower frequency of the TGCG haplotype, and a higher frequency of the GGCG and GAAA haplotypes in patients, thus conferring protection from or a susceptibility to RSM by these haplotypes respectively. Regression analysis confirmed the association of TGCG [OR (95%CI)=0.09 (0.05-0.16)], and GGCG [OR (95%CI)=2.52 (1.34-4.54)] and GAAA [OR (95%CI)=4.02 (2.20-7.70)] haplotypes, after adjusting for age and BMI. Our findings indicate that IL-21 is a novel susceptibility gene for RSM.
  European cytokine network. 06/2011; 22(2):123-6.
• Source

  Available from: Wassim Y Almawi

  Article: Common polymorphisms of calpain-10 and the risk of Type 2 Diabetes in a Tunisian Arab population: a case-control study.

  Intissar Ezzidi, Amira Turki, Safia Messaoudi, Molka Chaieb, Maha Kacem, Ghada M Al-Khateeb, Touhami Mahjoub, Wassim Y Almawi, Nabil Mtiraoui
  [show abstract] [hide abstract]
  ABSTRACT: Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D). We examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP. Enrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls. CAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians.
  BMC Medical Genetics 01/2010; 11:75. · 2.33 Impact Factor