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العنوان
Genotyping of Mannose-Binding Lectin variant alleles
in Egyptian infants with acute respiratory tract infections
المؤلف
Esa,Mohamed Ahmed
هيئة الاعداد
باحث / Mohamed Ahmed Esa
مشرف / Rabah Mohamed Shawky
مشرف / Sherine Mohamed Abd El-Fattah
مشرف / Tarek Mostafa Kamal
الموضوع
acute respiratory tract infections-
تاريخ النشر
2011
عدد الصفحات
147.p:
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب الأطفال ، الفترة المحيطة بالولادة وصحة الطفل
تاريخ الإجازة
1/1/2011
مكان الإجازة
جامعة عين شمس - كلية الطب - Pediatrics
الفهرس
Only 14 pages are availabe for public view

from 147

from 147

Abstract

Acute respiratory infections (ARI) are a major cause of morbidity and mortality in young children world wide. They account for nearly 3.9 million deaths every year globally. On an average a child has 5 to 8 attacks of ARI annually. ARI accounts for 30-40% of the hospital visits by children in office practice
Mannose-binding lectin (MBL) is a key molecule in innate immunity with the capacity to bind to a broad range of microorganisms and subsequently kill them by initiating the lectin pathway of complement activation .
As a first-line defense, MBL seems to be particularly important , when adaptive immunity is not yet fully developed. Several variations in the gene encoding MBL have been described, mostly single-nucleotide polymorphisms. Three polymorphisms have been found in exon 1 of the MBL gene at codons 52, 54, and 57.
Two common polymorphisms (H⁄ L and Y ⁄ X) identified in the upstream promoter region also determine serum levels by regulating protein expression (Madsen et al., 1995). Different combinations of these polymorphisms result in a wide range of serum levels, from undetectable to 2–3 log orders of magnitude in healthy individuals. Therefore the prevalence of common gene polymorphisms in the human MBL2 gene has resulted in a great natural variation of circulating MBL levels, which therefore represents one of the most dramatic examples of inter-individual variation in an innate immune molecule. As the initial discovery that MBL deficiency was associated with recurrent infections in children, the impact of the variations in MBL genotypes or serum concentrations on different human diseases has been intensively studied .
This study is a case control study aiming at Characterization of the structural alleles of MBL2 gene located on chromosome 10 (high- and low-MBL expression genotypes), Trying to make a correlation between genotyping of MBL2 alleles(cd54, promoters (LX, HY, LY) ) and occurrence of respiratory tract infections and sepsis in Egyptian infants ,trying to find out the most prevalent MBL2 variant alleles among the Egyptian samples in study.
The study group: included 24 neonates with amean age of 0.21+-0.19 with range from 0.07 to 0.73 and 25 infants with mean age of 9.65+-8.5 and range from 1month to 24 monthes .
All of them will be subjected to Full history taking, Thorough clinical examination, blood count, Erythrocyte sedimentation rate, Chest-X ray, C-reactive protein, Blood culture when indicated, DNA isolation from peripheral blood samples, Molecular gene analysis on DNA for characterization of MBL2 gene on chromosome 10& Characterization MBL2 variants alleles through the application of PCR-based mutation analysis and sequencing when indicated.
Our results reveals the following characteristics in the study group:
There was a statistically significant difference between ICU neonates and infants groups regarding to hemoglobin levels, PNL, Lymphocytes and MCV; all theses parameters were significantly lower in infants group except for Lymphocytes which was higher among infants group . On the other hand, there were no statistically significant differences between ICU neonates and infants groups regarding to RBCs and WBCs.
There was no statistically significant difference between ICU neonates and infants groups regarding to the C reactive protein status.
60% of ICU neonates showed normal chest x-ray while 92% of infants showed exaggerated broncho-vascular markings. Moreover, 20% of infants and 24% of ICU neonates had pneumonic patches. Only 8% of ICU neonates showed exaggerated broncho-vascular markings. These differences were statistically significant.
The incidence of cyanosis among ICU neonates was 9/25 (36%) compared to 5/25 (20%) among infants. This difference in the incidence of cyanosis was not statistically significant.
The incidence of grunting among ICU neonates was 20/25 (80%) compared to 14/25 (56%) among infants. This difference in the incidence of grunting was not statistically significant.
ICU neonates were associated with higher grades of respiratory distress compared to infants; grade III in 56% of ICU neonates compared to 44% of infants and grade IV in 36% of ICU neonates compared to 16% of infants. These differences were statistically significant.
ICU neonates showed significantly higher respiratory rate compared to infants (Figure 11). However, infants showed higher heart rate than ICU neonates with no statistically significant difference.
The control group: included 25 healthy infants.
Our results revealed that there was a statistically significant increase in LX promoter among patients (59.2%) compared to controls (28%). However, there were no statistically significant differences regarding to HY or LY promoters between patients and controls.
It showed that there was no statistically significant difference in the distribution of MBL codon 54 polymorphism between patients and controls in this study. However, the most prevalent RFPL genotype in both groups was the wild one
showed no statistically significant relationship between MBL promoters and the grades of respiratory distress in ICU neonates or infants. However, grade III respiratory distress was the most prevalent one among all MBL promoters.
It also showed no statistically significant relationship between MBL Codon 54 genotypes and the grades of respiratory distress in ICU neonates. However, grade III & IV respiratory distress were the most prevalent ones among all MBL Codon 54 genotypes.
There was no statistically significant relationship between MBL Codon 54 genotypes and the grades of respiratory distress in infants. However, grade II & III respiratory distress were the most prevalent ones among all MBL Codon 54 genotypes.