One of the most prevalent forms of dementia is Alzheimer's disease (AD). Complex inheritance and multifactorial patterns of late-onset AD (LOAD) along with its heterogeneity are due to the presence of different AD-predisposing genes with different influence on disease development among various populations. A key event in the pathogenesis of AD is the deposition of β-amyloid peptide, which is derived from the amyloid precursor protein by β- and γ-secretases. Cathepsin D (CTSD) is an acid protease with β- and γ-secretase-like features in vitro. An exonic C→T polymorphism at position 224 of the CTSD gene (rs: 17571) has been shown to be associated with the enzyme function of CTSD and with AD. Two studies in the German population reported a strong association of this polymorphism with an increased risk of developing AD, while other studies did not confirm this observation. We tested for this association in a case-control study in 100 Iranian sporadic LOAD patients based on diagnostic criteria of DSM-IV-TR and NINCDS-ADRDA and in 100 normal controls without any personal and family history of AD or other related dementias. Polymerase chain reaction-restriction fragment length polymorphism was set up to detect this polymorphism. Our study demonstrated that T-carrying genotype frequency in AD patients is significantly higher than in controls and there was a 2.5-fold increased risk for developing AD in the T-carrying genotype compared to C/C genotype (odds ratio = 2.5, p = 0.010). The odds ratio for subjects with the apolipoprotein E ε4 (APOE ε4) allele was 2.91 (p = 0.003) and carriers of the CTSD T and APOE ε4 alleles had a 6.25-fold increased risk of the disease (p = 0.0). Our results indicate that CTSD genotype is associated with the disease and a combination of the above risk factors significantly alters the risk for developing AD.
Secondary chromosome aberrations in de novo acute myeloid leukemia ( AML) are less specific and occur in addition to the primary chromosome abnormalities. Secondary chromosome aberration in acute nonlymphocytic leukemia has been recognized for many years as the most serious long-term complication of malignant disease. Our aim in this study was to focus on patients with AML associated with secondary chromosomal abnormalities in 127 consecutive Iranian leukemia patients. Methotrexate (MTX) cell synchronization and 24h non-stimulated cultures of bone marrow cells were applied to determine the incidence of chromosomal aberrations and association of specific primary and secondary chromosome anomalies according to French American British (FAB) morphological subtypes. The distribution of the secondary changes was clearly non-random. The most frequent numerical changes were -X, - Y, -7, + 8, -10 and + 22 and the most common structural aberrations were i(17q), 9q-, dicentric and marker chromosome. We believe this report is the first for de novo AML patients showing secondary chromosomal abnormalities which are quite non-random. The findings could contribute to widening knowledge of related chromosomal abnormalities.
Childhood Hepatitis B virus (HBV) infection causes both medical and public health challenges. Infants who acquire HBV parentally have up to 90% risk of developing chronic HBV infection. It is now estimated that approximately 10% of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. In this distribution, elevated rate and prevalence of HBV marker have been found in patients with malignancies as compared to the general population. By reviewing the web-based search for all Persian and English types of scientific peer review published articles initiated using Iran Medex, MEDLINE/PubMed, CINAHL and other pertinent references on websites about HBV and HCV blood disorders. The high prevalence of HBV and HCV infective markers was detected in patients with different malignancies. Moreover, identification of high prevalence of HBV infective markers in leukemia patients proposed strong association between hepatitis viral infections and leukemia.
Cystic fibrosis (CF) is the most common inherited disorder in Caucasian populations, with over 1400 cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The type of mutations and their distributions varies widely between different countries and/or ethnic groups. Seventy Iranian cystic fibrosis patients were screened for the CFTR gene mutation using ARMS/PCR (amplification refractory mutation system) for the following mutations: deltaF508, N1303K, G542X, 1717-1G>A, R553X, W1282X, G551D, 621+1G>T, deltaI507 and R560T. Single strand conformation polymorphism (SSCP) analysis of exons 3, 7, 10, 11 and 17b, including both the exon/intron junctions, of the CFTR gene was performed in patients in whom no mutation could be identified on one or both CFTR genes. As a result of this screening, only three mutations were found: deltaF508 mutation was found in 25 (17.8%) alleles, N1303K in six (4.3%) alleles and G542X in five (3.6%) alleles. Thus, a total of 3 mutations cover 25.7% of CF alleles. These finding will be used for planning future screening and appropriate genetic counseling programs in Iranian CF patients.
Alzheimer’s disease is the most common form of dementia with polygenic disposition occurring within various populations. A series of molecular studies indicated that there are number of genes linked to late onset Alzheimer’s disease (AD). In the current study, we examined the contribution of B2-AR (Gly16, Arg), TLR2 (-196TO-174del), PICALM (rs3851179) and BDNF (rs6265) alleles and genotypes, and their relevance in response to Rivastigmine in 150 Iranian AD patients and 150 controls.
The association of the Graves disease (GD) with HLA DR3 and DQA1*0501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB1*0301 and DQA1*0501 alleles conferred significant susceptibility in the DRB1*0301-DQA1*0501 haplotype. The DRB1*0301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA1*0501 was most likely due to it being in linkage disequilibrium with DRB1*0301. The DRB1*0701/x and DQA1*0201/x genotypes and the DRB1*0701-DQA1*0201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD.
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