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|Title||Endothelial Nitric Oxide Synthase "eNOS" Gene Polymorphisms, Nitric Oxide and Progesterone levels in Idiopathic Recurrent Pregnancy Loss|
Pregnancy is a hypercoagulable state with increased tendency for thrombus formation, a condition that is increased when combined with acquired or inherited risk factors that lead to thrombophilia. Recurrent pregnancy loss (RPL) is an important clinical and stressful problem that has been studied tremendously but the causes and treatment have not been fully resolved. RPL affects about 1-5% of women who conceiveand accounts for about 20% of clinically recognized pregnancy losses. Despite extensive researches to explain the causative effects of RPL, about 50%-60% of RPLs are still idiopathic. The association between endothelial nitric oxide synthase (eNOS) polymorphism, their haplotypes, serum nitric oxide (NO) levels and RPL, were studied in different ethnic populations. The results, however, were contradictory. Objective: This study was conducted in order to determine the association between promoter -786 T>C, exon 7 Glu298Asp (894 G>T) and intron 4 (4a4b) VNTR polymorphismsof eNOS gene, serum NO and progesterone (P4) levels, and idiopathic RPL in Palestinian women residing in Gaza strip. Method: This study is an association study with a case-control design. The study population consisted of 45 (30 non-pregnant and 15 pregnant) women who suffered from unexplained RPL, and 45 (30 non-pregnant and 15 pregnant) healthy women matched for age and without previous history of RPL. Blood samples collection were carried out during the period from June2011 to September 2011. Two blood samples werecollected from each subject after fasting for 10-12 hours, one was whole blood and the other was serum.DNA was extracted from whole blood samples. The PCR products of intron 4 (4a4b) VNTR polymorphismwere analyzed by allele-specific PCR, where it separated electrophoretically using ethidium bromide-stained 2% agarose gel. However, the PCR products of exon 7 Glu298Asp (894 G>T) and promoter -786T>C polymorphismsby PCR-RFLP, where they digested using specific restriction enzymes and then separated electrophoretically using 2% agarose gel. Serum NO levels were measured spectrophotometrically, and P4 levels were measured using Immulite 1000 Analyzer. Results: The C allele carrierwhich represented by (CC + CT) genotypes and the C allele of the promoter -786T>C polymorphism are significantly associated with increased risk of RPL, where they presented with a higher frequency in RPL women and were associated with decreased serum NO levels in this group (all P-values <0.001). Neither exon 7 Glu298Asp(894G>T) nor intron 4 (4a4b) VNTR polymorphism was significantly associated with RPL risk in the study population. The serum NO levels were lower in RPL patients as compared to their respective controls (P-value =0.004). The study pointed to the presence of a positive proportional correlation between serum NO and P4 levels in the study population (P-value= 0.002, Correlation coefficient= 0.319) that might be attributed to the presence of a putative progesterone receptor binding site in the upstream promoter region of eNOS. The study also showed that the promoter -786T>C polymorphism was not associated with P4 level in the study population. Conclusion: The (CC + CT) genotypes (C allele carrier)and the C allele of the promoter -786T>C polymorphismare possible risk factors for RPL. The study showed that the (C allele carrier) which represented by (CC + CT) genotypesis associated with a decreased serum NO level that, in turn, is associated with RPL. Moreover, a positive proportional correlation between serum NO and P4 levels was evident.Therefore, balancing P4 and NO levels may be of benefit for maintaining pregnancy in those cases.
|Publisher||the islamic university|
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