الفهرس 
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Abstract
Sharp and colleagues first described an association between AAT deficiency and cirrhotic liver disease in 1969.
AAT is a 52-kD glycoprotein comprising a single chain of 394 amino acid residues and three asparagine-linked complex-carbohydrate side chains.
AATD is an autosomal-recessive metabolic disease that results from mutations on the protease inhibitor (Pi) locus, with encoded gene 14q31-32.3. The polymorphism described on this gene gives rise to protein variants. The gene is organized into three noncoding exons (Ia, Ib, and Ic) and four coding exons (II, III, IV, and V) through six introns (Blank et al., 1994). The open reading frame is located in the last four exons and codes for 418 amino acids. The first 24 amino acids form a signal peptide, which is cleaved during intracellular processing, resulting in a 394 amino acid-long mature protein.
The normal gene is designated PiM and is highly pleomorphic, with more than 100 normal and deficiency alleles having been identified using assays based on isoelectric focusing. The two most frequent mutations on the Pi locus are the PiZ (Glu342Lys) and the PiS (Glu264Val), compared with M-phenotype subjects.
This case control study was designed to determine the prevalence of Alpha 1 antitrypsin deficiency (AATD) in patients with chronic liver disorders.
The study also aimed to estimate the frequency of Alpha 1 antitrypsin (AAT) gene polymorphism in Egyptians to investigate the possible role of the proteinase inhibitor PiS and PiZ AAT alleles in the progression of chronic liver disorders.
The studied subjects were divided into four groups; group (I) included 32 cirrhotic patients, 16 males and 16 females. Their ages ranged from 34 to 69 years old (mean= 46.06 ± 9.29) years. group (II) included 20 fibrotic patients, 15 males and 5 females. Their ages ranged from 39 to 68 years old (mean= 46.15 ± 8.06) years. group (III) included 15 cirrhotic/fibrotic patients, 8 males and 7 females. Their ages ranged from 35 to 63 years old (mean= 49.35± 8.28) years. And group (IV) included 20 normal subjects as control, 14 males and 6 females. Their ages ranged from 36 to 52 years old (mean= 43.55± 4.52) years.
All patients were examined clinically and assessed serologically for liver functions, HBV and HCV infections, serum AAT levels were estimated by immunonephelometric method and genotyping of proteinase (Pi) Z and S alleles were detected by Conventional (ARMS-PCR).
Regarding the age and gender distributions in the current study, there was no statistical difference among the studied groups. The result was statistically insignificant, owing to the small sample size of this study (p > 0.05).
Regarding liver functions (total bilirubin, direct bilirubin, AST, ALT, PT, PC, serum albumin and total protein), results were highly significant among the different studied groups (P < 0.01). While with ALP the result was statistically insignificant, (P =0.338: α ≥0.05).
Regarding the AAT level, this study showed that the level of AAT was lower in the cirrhotic, cirrhotic/fibrotic and the fibrotic groups in relation to the control group. Results were highly significant among the different studied groups (P < 0.01).
Regarding the Distribution of the results of HBsAg and HCV Ab among groups of the studied population, this study revealed that the frequencies of HBsAg among the studied groups were significantly different at (Chi-Square = 9.347: P-value= 0.025). And for HCV Ab, frequencies were significantly different at (Chi-Square = 57.724: P-value= 0.000).
Regarding the frequencies of AAT genetic polymorphism according to the Z allele (PiZ) among the studied groups, The AATZ genotypes in the four studied groups were not significantly different at (P-value> 0.05=0.339). However, their prevalence in the cirrhosis group was higher than in other groups. The PiZ mutant type allele was found in 3 patients (9.4%) and 1 patient (5.0%) of cirrhotic and fibrotic groups respectively, while The M wild type allele was found in 29 cirrhotic (90.6%), 19 fibrotic (95%), 15 cirrhotic fibrotic (100%) of the groups. In the control group the percentage of wild M type was 100 % i.e. presented in all subjects.
According to the S allele (PiS), all the patients and control groups showed a normal MM allele.
In the present study, no correlation has been found between the alpha 1 antitrypsin levels and the liver functions tests.
Regarding the PiZ allele distribution according to different age classes, there was no statistical difference among different age classes (Chi-Square = 0.049: P-value= 0.976). And according to the sex distribution no statistical difference could be detected (Chi-Square = 0.349: P-value= 0.555).
In conclusion, among Egyptian patients with chronic liver disorders, abnormal alpha 1 antitrypsin genotypes have been detected. These abnormal alleles could have possible enhanced effect on the progression of liver disease. Genetic and environmental modifiers are probably responsible for rendering the subgroup PiZ alpha 1 antitrypsin deficiency susceptible to liver disease.
Those affected patients with abnormal alleles should be protected from exposure to any potentially hazardous factors that can cause hepatic cell injury, e.g. hepatotoxic drugs or exposure to hepatotropic viruses.