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العنوان
Study of HLA-G genotypes in preeclampsia in relation to its mRNA expression in placental tissue
المؤلف
Ibrahim Mohammed ,Magda
هيئة الاعداد
باحث / Magda Ibrahim Mohammed
مشرف / Noura M. El Kholy
مشرف / Salah Taha Fayed
مشرف / Maha M. Sallam
مشرف / Hanan H. Shehata
الموضوع
Immune tolerance in pregnancy-
تاريخ النشر
2009.
عدد الصفحات
187.p:
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
1/1/2009
مكان الإجازة
جامعة عين شمس - كلية الطب - Medical Biochemistry
الفهرس
Only 14 pages are availabe for public view

from 187

from 187

Abstract

Pregnancy represents interesting phenomena not only in obstetrics and gynecology but also in the context of immunology. A central question in the immunology of pregnancy is how the fetal–placental unit avoids maternal immune rejection. Placental function contributes to the success of pregnancy in many recognized ways, such as their unusual expression of HLA class I proteins (class Ib). The lack of HLA class Ia and class II expression on trophoblasts could explain why the maternal T cells do not recognize trophoblasts as non self antigens.
HLA-G, one of class Ib genes, have a biological significance beyond its concepts on feto–maternal immune regulation. In successful pregnancy, HLA-G molecules inhibit NK cytotoxicity on the trophoblast cells. Although, HLA-G is almost monomorphic, few polymorphisms were reported. Low HLA-G expression was apparent in some of pregnancy complications as PE.
Preeclampsia (PE) is one of the leading complications in pregnancy, affecting between 2–7% of all population births. It is a progressive multisystem disorder that is unique to pregnant women. It is characterized by hypertension, edema, and proteinuria but the mode of presentation and rate of progression of the disease are extremely variable and if PE is not treated early, it may progress to eclampsia or epileptic like fits. PE is the leading cause of maternal mortality in developed countries and is associated with a five folds increase in perinatal mortality. PE is mostly confined to first pregnancies, and indeed the risk of PE in a second pregnancy is significantly reduced if the first pregnancy was normotensive. Although the symptoms of PE only become apparent in the third trimester of pregnancy, it is generally accepted that the underlying pathologic changes occur much earlier in the placenta and placental bed. Despite considerable research on preeclampsia, no obvious cause is known. The only treatment at present is removal of the fetus and placenta.
The aim of this work is to evaluate HLA-G polymorphisms as 14bp insertion/deletion polymorphism in 3’UTR & codon 258 SNP (single nucleotide polymorphism) in exon 4, and their relation to placental HLA-G expression in full term preeclamptic patients and normal pregnant women.
Placental tissue specimens from 50 full term pregnant women in labor attending the Maternity Hospital, Ain Shams University were included in this study.
The patient group included placental tissue specimens from 25 primigravid women with preeclampsia either mild (n=10) or severe (n=15). All of them had systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg and proteinuria with albumin in urine (+1or more).
The normal pregnant (NP) control group included placental tissue specimens from 25 healthy normotensive primigravid women.
The current results revealed a significant reduction in HLA-G expression in total and severe PE groups than NP group (P<0.05). Moreover, HLA-G expression was associated with the severity of disease as we found that severe PE had a significant lower expression than mild PE (P<0.05).
Using the cutoff value calculated from the ROC curve (56%), 23 out of 25 preeclamptic patients had their HLA-G normalized quantity below the cutoff value, while only 11 out of 25 normal pregnant subjects showed HLA-G values below the cutoff (P< 0.05).
Adding to this, HLA-G expression was negatively correlated to clinical data (as maternal age, systolic and diastolic blood pressures) (P<0.05). Meanwhile, HLA-G expression was positively correlated to birth weight and placental weight (P<0.05). Also, this was supported by finding that 16%, 18% reduction in birth weight and placental weight respectively could be explained by reduction in HLA-G expression.
In codon 258 SNP, little studies were available, this represent an obstacle in comparing our results to the others. No specific alleles was present either in NP or PE group (P>0.05). However, ATG allele was quietly less dominant in severe PE subgroup in comparison to NP group (P=0.08). Also, the association of 14bp genotype with codon 258 alleles was performed. The frequency of ACG allele was significantly higher in +14/+14bp genotype than in any other genotype (P<0.05).
The effect of codon 258 alleles on HLA-G expression and pregnancy outcome in all subjects was evaluated. No significant difference in HLA-G expression and pregnancy out come was observed either in ACG or ATG allele. However, placental weight in ACG allele was nearly lower than ATG allele (P=0.07).
ACG& ATG alleles in PE group had significant lower birth weight and placental weight in than their corresponding alleles in NP group (P<0.05). As regards HLA-G expression, ACG allele in PE group had a significant lower value than those with ACG allele in NP group (P<0.05). As regards both alleles in PE only, no significant difference was detected either in pregnancy outcome (birth weight and placental weight) or in HLA-G expression (P>0.05). The previous finding was, also, found in both alleles in NP only (P>0.05).
As regards 14bp insertion/deletion polymorphism, no dominant genotype or specific allele was detected in NP or PE groups (P>0.05). Also, the same result was exist in mild and severe PE (P>0.05).
The effect of 14bp polymorphism on HLA-G expression was demonstrated. Taking our subjects as whole, we found that -14/-14bp genotype had the highest level of expression (mean= 51±20.6) then +14/-14bp genotype (mean= 44.6±29.3) followed by +14/+14 genotype (mean= 34.7 ± 24.1). However, this significant difference in expression was present between -14/-14bp genotype and +14/+14bp genotype (P=0.07). Moreover, all 14bp genotypes in PE group had significant lower expression than the corresponding genotype in NP group (P<0.05). However, in PE group only, no significant HLA-G expression was found among 14bp genotypes (P>0.05).
The impact of 14bp insertion/deletion polymorphism on pregnancy outcome was discussed. As regards birth weight in all subjects, -14/-14bp genotype had significant higher birth weight than other 14bp genotypes (P<0.05). While this difference was absent in placental weight (P>0.05).
When NP and PE groups were analyzed separately, birth weight and placental weight of all 14bp genotypes in NP group was higher than the corresponding genotypes in PE group (P<0.05). However, in PE group only, both of -14/-14bp and +14/-14bp genotypes had nearly equal birth weight and +14/+14bp genotype had the lowest birth weight. In NP group only,-14/-14bp genotype had the highest birth weight then +14/-14bp genotype followed by +14/+14bp genotype. Meanwhile, the placental weight had the same direction either in PE or NP groups. Finally, we thought that -14/-14bp genotype might be the genotype with better pregnancy outcome.