Prevalence and molecular characterization of Glucose-6-Phosphate dehydrogenase deficient variants among the Kurdish population of Northern Iraq

<p>Abstract</p> <p>Background</p> <p>Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds.</p> <p>Methods</p> <p>A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C→T), G6PD Chatham (1003 G→A), G6PD A- (202 G→A), G6PD Aures (143 T→C) and G6PD Cosenza (1376 G→C), as well as the silent 1311 (C→T) mutation.</p> <p>Results</p> <p>Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and 10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases.</p> <p>Conclusions</p> <p>The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to those reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries.</p

Genetic Variants of Human Granzyme B Predict Transplant Outcomes after HLA Matched Unrelated Bone Marrow Transplantation for Myeloid Malignancies

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41–0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27–0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47–0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35–1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT

Telomerase and it&apos;s inhibition in caner: a review article

&quot;n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Telomere, by which is a terminal structure of eukaryotic chromosomes was discovered at first in 1938 and has a vital role in chromosome protection. Telomere in human and other vertebrates consists of thousands of 5&amp;prime;-TTAGGG-3&amp;prime; tandem repeats at the end of the chromosome, has a main role in the chromosome stability. Telomere protects the end of the chromosome from degeneration, rearrangement and end to end fusion. There is a telomere loss at every cell division. Progressive loss in telomere length results in disassociation of telomere binding proteins and change in gene expression profiles. Adjacent genes are suppressed by the telomere effect so the telomere loss results in adjacent gene expressions. Apoptosis and replicative senescence are caused by progressive telomere loss. There are three mechanisms for increasing telomere length in eukaryotes and telomerase is the predominant mechanism. Telomerase can synthesize telomere, without the template. Telomerase is overexpressed In 90% of cancers. Therefore cancerous cells compensate the telomere loss in every cell division because of telomerase. In conclusion, telomerase is a proper target for cancer therapy and many methods including direct inhibition of telomerase and immunotherapy have been introduced

Molecular genetic, diagnosis, prevention and gene therapy in prostatic cancer: review article

&quot;nThe prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced

Cancer metastasis, genetic and microenvironmental factors of distant tissue: a review article

Cancer is one of the main reasons of mortality worldwide, and more than 90 percent of cancer deaths are due to metastasis. Although primary tumors are curable using chemical adjuvant therapy or surgery, metastatic tumors are mostly incurable. This resistance shows the high rate of mortality among patients with metastatic disease. Being a sequential event, metastasis is a subtle and intricate process in which tumor cells undergo a plenty of changes and acquire the capacity of migration, invasion, survival and self-renewal which all are necessary for metastasis to happen. The key point in recognition and cure in invasive cancers is to identify critical genes, proteins and pathways involved, and show their relation with each other and the disease. Forming metastasis needs favorable genetic and microenvironmental elements of tumor cells and distant tissue, respectively. Unfavorable conditions in each steps of this process lead to arresting metastasis and subsequent dormancy, which is the most important phenomenon in relapse. In this review, benefiting from tens of reliable and recently identified data and personal experiences, it has been tried to draw new patterns associated with metastasis for further investigation. Determining genes, proteins and microenvironmental factors that affect metastasis, in a sequential manner, can help better understanding of this lethal process and subsequently a prosperous treatment

Metabolic activation and DNA adduct formation of Benzo (?) Pyrene by adult and newborn rat skin and liver microsomes

Abstract: Benzo (?) Pyrene is a carcinogen polycyclic aromatic hydrocarbon which diffuses into the environment from combustion of organic materials. Based on various epidemiological evidences it is related to lung, skin and liver cancer. Mutagenicity, and immunosuppressivity are among important biological effects of Benzo(?) pyrene. After absorption and distribution on the body, it undergoes epoxidation by cytochrome P-450 system in the cells. Some of the electrophilic metabolites covalently bind to cellular macromolecules and in particular to DNA. Its metabolites are partially detoxified by conjunction to cellular glutathione (GSH), glucoronic acid, and sulphate. Biological effects of B (?) P and its metabolites depend on various factors such as species, age, sex, tissue, diet, dose, genetic system, etc. The fundamental physiological differences between newborns and adults are variations in susceptibility to chemical carcinogens observed between the two age groups. In this paper we studied the level of binding of B(?) P to calf thymus DNA and formation of DNA adduct in the incubation systems which contained adult and newborn rat liver and skin microsomes. Results indicate that in both age groups liver microsomes in comparison to skin microsomes cause a higher increase in the level of DNA adduct and the ratio of DNA adduct in the liver of adults compared to animal skin was 4.2 to 1. The quantity of adduct in the incubation systems containing liver microsomes of newborn was 1.51 higher than that of skin microsomes. Moreover phenobarbiton failed to induce cytochrome P-450 and any increase in DNA adduct level of B(?) P in the newborns rat. The level of cytochrome P-450 in adults liver was 2.86 times higher than that in newborns’ liver. Keywords: Benzo (?) Pyrene, DNA, Newborn, Adult, Phenobarbito