الفهرس 
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Abstract
Recurrent pregnancy loss (RPL) is the most common complication of human gestation, affecting about 1–5% of women worldwide. It is defined as two or more consecutive spontaneous abortions before week 20 of pregnancy. Genetic, anatomic, endocrine, and immune defects as well as infections have been proposed as causes for RPL. After evaluation of all causes, approximately half of all cases will remain unexplained.
Thrombophilias are inherited or acquired conditions that predispose an individual to thromboembolism, which can be found in more than 50% of women suffering from RPL of unknown cause. The most widely reported inherited thrombophilias have been factor V Leiden and factor II prothrombin mutations. Several other polymorphisms and mutations have been associated with RPL including coagulation factor XIII (FXIII) and PAI-I.
PAI-1 is the primary physiologic inhibitor of plasminogen activation in blood targeting u-PA and t-PA. The human gene for PAI-1 is located on chromosome 7 (q21.3-22). A polymorphism located 675 bp upstream of the transcription start site consists of a single guanine insertion/deletion variation (4G/5G) leading to a sequence of four or five guanine nucleotides in the promoter. Individuals homozygous for the 4G polymorphism have the highest levels of PAI-1, heterozygotes show intermediate levels, and those homozygous for the 5G allele have the lowest levels. The basis of this differential expression of the PAI-1 gene appears to be the specificity of a transcriptional repressor protein that binds the 5G allele and not the 4G allele.
Factor XIII or Fibrin Stabilizing Factor functions as a transglutaminase that can form cross-linked amide bonds between specific glutamine and lysine residues on polypeptide chains. Plasma factor XIII circulates as a heterotetramer composed of two A-chains and two B-chains. The gene for the factor XIII A subunit is located on chromosome 6(p24-25), while the gene for B subunit is located on chromosome 1(q31-32.1). The most common polymorphism affecting the FXIII gene involves a G-to-T transition (FXIII G103T) in exon 2 of the gene encoding for FXIIIA, which leads to a valine (V)-to-leucine (L) substitution at amino acid 34; the (Val34SLeu) polymorphism in the A subunit is found in approximately 25% of the population.
This study aimed to elucidate the association of PAI-I 4G/5G polymorphism and FXIII Val34Leu polymorphism with idiopathic RPL to allow proper management and genetic counseling for the high risk carriers.
The present study was conducted on two groups;
- Cases group which included 50 women with at least 2 consecutive repeated abortions, that were referred to the Human Genetic Department, Medical Research Institute, Alexandria University for genetic counseling.
- Control group which included 50 unrelated fertile females that were randomly selected from the general population, who had experienced at least a single healthy live birth, without any obstetric complication with no history of pregnancy loss and were matched for cases regarding age and ethnicity.
The 2 study groups were subjected to careful history taking and clinical genetic examination. Both groups were included in the molecular study using PCR/RFLP technique for detection of the PAI-I4G/5G and FXIIIVal34Leu polymorphisms.
The results of this study revealed the following:
• The mean age in the case group was 31 years (18-44 years), while among controls the mean age was 31.5 years (21-42 years). As regards cases group, the number of pregnancy loss ranges from 2 -11 times (mean 6.5 times).
• For PAI-I 4G/5G polymorphism, two alleles were present ( 4G and 5G) and two different genotypes (5G/5G and 4G/5G), the third genotype 4G/4G could not be detected in any of the studygroups . Forty two percent of the studied cases (21/50) had one mutant allele (4G/5G genotype), while thirty four percent of the studied controls (17/50) had one mutant allele (4G/5G genotype); heterozygosity carriers.
• The commonest allele in both groups is 5G allele, it is more common among the control group than the cases group. The 4G allele frequency is higher among cases group. Among cases the 5G allele frequency was 79% and the 4G allele frequency was 21%, while in the control group the 5G allele frequency was 83% and the 4G allele frequency was 17%. The 4G/5G genotype is higher among cases group, but the association between PAI-1 -675 4G⁄5G polymorphism and repeated pregnancy losses is considered to be not statistically significant.
• For the FXIII (G103T) polymorphism, two alleles were present (G (Val) and T (Leu) and two different genotypes (Val/Val and Val/ Leu), the third genotype Leu/Leu could not be detected in any of the study groups. Eighteen percent of the studied cases (9/50) had one mutant allele (Val/Leu genotype), while only twelve percent of the studied controls (6/50) had one mutant allele (4G/5G genotype); heterozygosity carriers.
• The commonest allele in both groups is Val allele, it is more common among the control group than the cases group. The Leu allele frequency is higher among cases group. Among cases the Val allele frequency was 91% and the Leu allele frequency was 9%, while in the control group the Val allele frequency was 94% and the Leu allele frequency was 6%. The Val/Leu genotype is higher among cases group, but the association between XIII Val34Leu polymorphism and repeated pregnancy losses is considered to be not statistically significant.
• Only two patients and none of the controls were identified to be double heterozygous carriers for the two polymorphisms; PAI4G/5G and FactorXIIIVal34Leu and the combined occurrence of both polymorphisms is considered to be not significantly associated with RM