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Microbial L-asparaginase is well known for its application in food industries to reduce acrylamide content in fried starchy food. L-asparaginase produced by Arctic actinomycetes Streptomyces koyangensis SK4 was purified and studied for biochemical characterization. The L-asparaginase was purified with a yield of 15.49% and final specific activity of 179.77 IU/mg of protein. The enzyme exhibited a molecular weight of 43 kDa. The optimum pH and temperature for maximum activity of the purified enzyme were 8.5 °C and 40 °C, respectively. The enzyme expressed maximum activity at an incubation period of 30 min and a substrate concentration of 0.06 M. The enzyme has a low Km value of 0.041 M and excellent substrate specificity toward L-asparagine. The enzyme activity was inhibited by metal ions Ba2+ and Hg2+, while Mn2+ and Mg2+ enhanced the activity. The study evaluated the acrylamide reduction potential of L-asparaginase from Streptomyces koyangensis SK4 in potato chips. The blanching plus L-asparaginase treatment of potato slices resulted in a 50% reduction in acrylamide content. The study illustrated an effective acrylamide reduction strategy in potato chips using L-asparaginase from a psychrophilic actinomycete. Besides the acrylamide reduction potential, L-asparaginase from Streptomyces koyangensis SK4 also did not exhibit any glutaminase or urease activity which is an outstanding feature of L-asparaginase to be used as a chemotherapeutic agent.
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Asparaginasa , Streptomyces , Asparaginasa/genética , Asparaginasa/metabolismo , Acrilamida/química , Acrilamida/metabolismo , Streptomyces/metabolismo , TemperaturaRESUMEN
Quinoline and imidazole derivatives have been playing a significant role in functional bioactivities and were potentially used as antibacterial, antifungal, anticancer, and anti-inflammatory drugs. Owing to the limitation of drug resistance, herein we synthesized thio-, chloro-, and hydroxyl-functionalized various imidazoquinolines by molecular hybridization approach. All the imidazoquinoline derivatives were examined for their antibacterial activity against selected bacterial pathogens by the agar well diffusion method. In addition, the anti-oxidant efficacy of imidazoquinolines was also tested using ferric reducing antioxidant power (FRAP). Among them, electron-withdrawing (-Cl) substituent containing imidazoquinoline 5f showed higher antibacterial and anti-oxidant activities than other imidazoquinolines and reached the effectiveness of the standard. In addition, compounds 4f, 5e, and 3f showed moderate antibacterial activity and other derivatives displayed weak activity against various pathogens. Molecular docking studies were also performed on selected imidazoquinoline derivatives (3f, 4f, and 5f), which showed high docking score and strong binding energy values. These results revealed that thio-imidazoquinoline could assist as a prototype for the designing of multidrug-resistant antibiotics against various microbial organisms.
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Kongsfjorden, an Arctic fjord is significantly affected by the glacier melt and Atlantification, both the processes driven by accelerated warming in the Arctic. This has lead to changes in primary production, carbon pool and microbial communities, especially that in the sediment. In this study, we have examined the bacterial community structure of surface (0-2 cm) and subsurface (3-9 cm) sediments of Kongsfjorden using the high throughput sequencing analysis. Results revealed that bacterial community structure of Kongsfjorden sediments were dominated by phylum Proteobacteria followed by Bacteroidetes and Epsilonbacteraeota. While α- and γ-Proteobacterial class were dominant in surface sediments; δ-Proteobacteria were found to be predominant in subsurface sediments. The bacterial community structure in the surface and subsurface sediments showed significant variations (p ≤ 0.05). Total organic carbon could be one of the major parameters controlling the bacterial diversity in the surface and subsurface sediments. Functional prediction analysis indicated that the bacterial community could be involved in the degradation of complex organic compounds such as glycans, glycosaminoglycans, polycyclic aromatic hydrocarbons and also in the biosynthesis of secondary metabolites.
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Bacterias/aislamiento & purificación , Sedimentos Geológicos/microbiología , Regiones Árticas , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Carbono/análisis , Carbono/metabolismo , Sedimentos Geológicos/química , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota , Filogenia , Metabolismo SecundarioRESUMEN
Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor invasion and progression. MMP-9 is a member of the MMP family and is also known as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic activity against type IV collagen, a major component of the basement membrane. Our study aims to examine the association of Gelatinase B (-1562C > T) promoter polymorphism with breast cancer invasion and progression. The study involves 200 breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T (rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase chain reaction and gel electrophoresis. The genotypes were determined and compared between patients and controls, and the influence of the polymorphism on clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9 polymorphism was detected more frequently in breast cancer patients than controls (p < 0.001). Our results suggest the clinical importance of MMP-9 gene polymorphism (-1562C > T) in breast cancer patients. The study may also help in identifying individuals at risk of developing breast cancer.
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Neoplasias de la Mama/genética , Progresión de la Enfermedad , Metaloproteinasa 9 de la Matriz/genética , Invasividad Neoplásica/genética , Adulto , Anciano , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Polimorfismo Genético , Pronóstico , Regiones Promotoras GenéticasRESUMEN
The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M and GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.
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Glutatión Transferasa/genética , Leucemia Mieloide Aguda/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Eliminación de Secuencia , Adolescente , Adulto , Estudios de Casos y Controles , Niño , ADN/análisis , ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Renin is a rate-limiting enzyme of the renin-angiotensin-aldosterone system (RAAS) that plays a crucial role in the regulation of blood pressure. The renin gene has been suggested as a marker for genetic predisposition to essential hypertension (EHT) in humans. The purpose of the study is to explore the association of a genetic marker of renin gene Mbo I polymorphism with EHT in the South Indian population. METHODS: A total of 279 hypertensive and 200 normotensive subjects were genotyped for REN Mbo I polymorphism (RFLP) using the PCR-restriction fragment length polymorphism method. RESULTS: There were no significant differences in the distribution of genotypes and alleles for REN gene Mbo I polymorphism between hypertensive cases and controls (p>0.05). The genotypic and allele frequencies were in Hardy-Weinberg equilibrium both in cases and controls. Females with Mbo I AA+GA genotypes had 1.87-fold higher risk to develop hypertension as compared with those with GG genotype (odds ratio 1.87; 95% confidence interval = 0.98-3.56, p = 0.057). CONCLUSIONS: Our results indicate that renin gene Mbo I site polymorphism is not associated with blood pressure levels and risk of hypertension. However, the present study demonstrates risk for females who are carriers of REN Mbo I A allele for developing essential hypertension.
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Desoxirribonucleasas de Localización Especificada Tipo II/genética , Predisposición Genética a la Enfermedad , Hipertensión/genética , Polimorfismo Genético , Renina/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Demografía , Hipertensión Esencial , Femenino , Frecuencia de los Genes/genética , Humanos , India , Masculino , Persona de Mediana Edad , Factores de Riesgo , Caracteres SexualesRESUMEN
BACKGROUND: TP53, located on chromosome 17p13, is one of the most mutated genes affecting many types of human cancers. Thus, we aimed at investigating the association of SNPs in TP53 gene with chronic myeloid leukemia (CML). MATERIALS AND METHODS: A total of 236 CML and 157 control samples were analysed for mutations in TP53 gene using polymerase chain reaction followed by direct sequencing. RESULTS: Sequencing analysis for mutations in exons 7-9 of the TP53 gene revealed four SNPs, three in intron 7 (C14181T, T14201G, and C14310T) and one SNP in intron 6 (A13463G) of TP53 gene. The mutation C14181T is located at position 72 base pairs downstream of the 3'-end of exon 7 of the P53 gene. This mutation is in complete linkage disequilibrium with a T14201G mutation, 20 base pairs further downstream occurring at position 14201. This mutation occurred only in the presence of C14181T mutation and these mutations showed association with advanced phase and cytogenetic poor response. Another two novel mutations, C14310T in intron 7 and A13463G in intron 6 were also found to be associated with cytogenetic poor response. CONCLUSION: Our study suggests that TP53 intronic SNPs might have a strong influence on disease progression and poor response in CML patients.
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TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (χ2- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.
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Codón/genética , Leucemia Mieloide Aguda/genética , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , ADN/genética , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Pronóstico , Factores de RiesgoRESUMEN
The pathogenesis of cataract is influenced by a number of factors including oxidative stress. Glutathione-S-transferase (GST) catalyses the nucleophilic addition of the thiol of GSH to electrophilic acceptors. It is important for detoxification of xenobiotics in order to protect tissues from oxidative damage. In humans, GSTT1 and GSTM1 deletion genotypes are associated with a variety of pathological conditions including certain ophthalmic diseases. In the present study, it is aimed to determine the risk of genetic polymorphisms of GSTM1 and GSTT1 isoforms of GST for developing of age related cataracts (ARCs). We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 455 patients with ARCs (108 with nuclear (NC), 105 with cortical (CC), 96 with posterior subcapsular, (PSC) and 146 with mixed type (MT)) and 205 age and sex matched controls. The GST activity in erythrocytes (RBC) and cataractous lenses was measured spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. The frequency of GSTM1 positive individuals was significantly higher in MT cataracts followed by NC, CC and PSC types with corresponding decrease in the GSTM1 null genotypes as compared to controls. Considering the GSTT1 locus, GSTT1 null genotypes showed high frequency in patients in general as compared to controls with corresponding reduction in the GSTT1 positive genotype. The activity of GST in RBC was higher in all the types of cataracts as compared to that in controls and in cataractous lenses the mean values were slightly higher in cases of NC cataracts as compared to CC, PSC and MT. The data suggests that GSTM1 positive, GSTT1 null and double null (GSTM1 null and GSTT1 null) genotypes may confer risk for the development of ARC. The increased activity of GST found in the present study could be due to a compensatory mechanism operating in response to increased oxidative stress.
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Envejecimiento , Catarata/enzimología , Catarata/genética , Glutatión Transferasa/metabolismo , Polimorfismo Genético , Adulto , Anciano , Cartilla de ADN/química , Membrana Eritrocítica/enzimología , Femenino , Genotipo , Glutatión Transferasa/genética , Humanos , Isoenzimas/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Prevalencia , Factores de RiesgoRESUMEN
INTRODUCTION: The human angiotensinogen (AGT) is a promising candidate gene for evaluating susceptibility to essential hypertension (EH). We aimed to assess the association of the variants of AGT gene and the extent of risk involved in developing EH. METHODS: A case-control study was designed to compare 279 hypertensive patients with 200 normotensive subjects. The frequency distribution of M235T and T174M polymorphisms of AGT gene was assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. A haplotype analysis was done to determine the risk conferred by the combination of alleles of the two polymorphisms for EH. RESULTS: The genotype distribution of the T174M variant differed significantly between hypertensives and normotensives, whereas genotypes of M235T variant did not show such difference. For M235T, MM genotype conferred an increase in risk for hypertension in women (odds ratios (OR) = 2.82; 95% confidence interval (CI) = 1.22-6.49). For the variant T174M, the TM genotype frequency was elevated in hypertensive females (36.5%) as compared to controls (18.8 %; P = .034). The 174M allele was more prevalent among female hypertensives than among female controls (0.20 vs. 0.12; P = .059). The haplotype analysis showed a significant association for the haplotypes of paired markers (M235 and 174M) with a χ(2) value of 8.037 (P = .045). CONCLUSION: Our findings suggest that the polymorphic variants of AGT gene-M235T and T174M-show association with hypertension.
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Angiotensinógeno/genética , Variación Genética , Hipertensión/epidemiología , Hipertensión/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Factores de Riesgo , Distribución por SexoRESUMEN
Ulcerative colitis and Crohn's disease are the two major forms of inflammatory bowel disease (IBD). A series of reports have hypothesized interplay of genetic and environmental factors in the pathogenesis of IBD. Polymorphism in the mannan-binding lectin-2 (MBL-2) gene is known to affect the structural assembly and function thereby predisposing subjects to various diseases. The present study was designed to evaluate effect of MBL-2 gene polymorphism on MBL levels and function in IBD patients. Genomic DNA was isolated from blood samples collected from 157 ulcerative colitis, 42 Crohn's disease and 204 control subjects. Genotyping for different polymorphic sites at exon1 of MBL-2 gene was performed by refractory mutation system-PCR and amplification followed by restriction digestion (PCR-RFLP). Serum MBL concentration and C4 deposition levels were estimated using ELISA. Mannan-binding lectin-2 genotypic variants were calculated in IBD and healthy controls. The frequency of single nucleotide polymorphisms at codon 54 was significantly higher in ulcerative colitis patients than controls (P < 0.0001). Ulcerative colitis patients with 'codon 54'-variation showed low serum MBL concentrations coupled with altered MBL function compared to controls. In conclusion, single nucleotide polymorphism in the MBL-2 gene is an important risk factor significantly affecting MBL levels and function in the development of ulcerative colitis among Indians.
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Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad , Lectina de Unión a Manosa/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colitis Ulcerosa/sangre , Colitis Ulcerosa/patología , Complemento C4/metabolismo , Lectina de Unión a Manosa de la Vía del Complemento/fisiología , Enfermedad de Crohn/sangre , Enfermedad de Crohn/patología , Femenino , Genotipo , Humanos , India , Masculino , Lectina de Unión a Manosa/sangre , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
We analyzed the length of the CAG repeats of the androgen receptor gene in Indian women with breast cancer, and compared the data with that of other populations across the world in an attempt to find a potential pattern of association. The study was undertaken on 1,408 individuals comprising 747 breast cancer patients and 661 control individuals recruited from three southern states of India: Andhra Pradesh, Tamil Nadu, and Karnataka. The comparison revealed no difference in mean length of the repeat between cases and controls in any of the three groups or in the analysis of pooled data. No significant difference between pre- and post-menopausal cases in any of the three groups or in the analysis of pooled data was observed. Most of the studies to date support either positive association (longer repeats--increased disease risk) or no association, and only 2 out of 20 studies reported negative association (inverse correlation between repeat length and disease risk). Comparison of these data with those from other populations revealed several interesting facts. Particularly notable is that repeat length shows association with breast cancer risk in a population-specific manner with most of the studies on American and Canadian women showing positive association, whereas those on Australian and Israeli women showing no association. Only one study had been conducted on other populations including Asians/South Asians; this restricted us from finding any patterns of association in these populations.
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Neoplasias de la Mama/genética , Estudios de Asociación Genética , Polimorfismo Genético , Receptores Androgénicos/genética , Secuencias Repetidas en Tándem , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Andrógenos/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , India , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia. MATERIALS AND METHODS: Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5*3 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5*3 polymorphism and acute leukemia. RESULTS: The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ(2)- 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL. CONCLUSION: The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.
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The p53 protein is at the center of cell regulatory pathways influencing transcription and activity of several replication and transcription factors. In exon 4 of the gene TP53, a codon 72 polymorphism causing an Arg/Pro substitution has been reported in breast and other cancers. This substitution is in the putative SH3 binding domain of p53 protein, influencing binding capacity and thereby functional properties. In the present investigation of a relatively large series of cases in India, the frequency of the homozygous arginine genotype (33.2%) was significantly higher in the breast cancer group as compared to controls (19.6%), χ2 =11.791 (P=0.003). Patients with premenopausal breast cancer had a more elevated frequency (41.1%) than postmenopausal cases (25.4%) although the genotype frequency distribution did not show significant variation with respect to hormonal receptor status. Elevation was greatest in patients in advanced stages of cancer. The hetrozygote frequency (Arg/Pro) was also found to be increased in overweight and obese women with breast cancer. TP53 codon 72 polymorphism might predispose individual for the development of breast cancer as well as to bad prognosis. Intronic variants may affect gene regulation through aberrant splicing or through disruption of critical DNA-protein interaction. While no significant association was observed with relation to CC genotype as well as C allele of G13964C intron polymorphism with breast cancer, the C allele frequency showed association with respect to other risk confounding factors which might play role in progression of breast cancer.
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Neoplasias de la Mama/genética , Codón , Intrones , Proteína p53 Supresora de Tumor/genética , Alelos , Arginina/genética , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , India , Persona de Mediana Edad , Estadificación de Neoplasias , Obesidad/genética , Polimorfismo GenéticoRESUMEN
The multidrug resistance (MDR1) gene product P-glycoprotein is a membrane bound protein that functions as an ATP-dependent efflux pump, transporting exogenous and endogenous substrates from the cells. Since it plays an important role in chemotherapy, there is an increasing interest in the possible significance of genetic variation in MDR1. Our main objective was to study the MDR1gene polymorphism at C3435T with reference to development and progression of acute leukemia. The present study included 290 acute leukemia cases, comprising of 147 acute lymphocytic leukemia (ALL), 143 acute myeloid leukemia and 249 age-sex matched control samples for the analysis of MDR1 C3435T polymorphism, by the PCR-RFLP method. The MDR1 genotype distribution revealed an elevated frequency of the TT genotype in ALL cases (51.7%) as compared to controls (28.9%), whereas AML group did not show any association. The mean white blood cell count, blast% and LDH levels were increased in ALL patients with the CC genotype. No deviation was observed with respect to hematoglobin, platelet count and disease free survival in ALL patients. The association of CC genotype with clinical variables in ALL indicated that the CC genotype with high expression might be eliminating antileukemic drugs (anthracyclines, Daunorubicin, Vincristeine, Mitoxanthrone) which are P-gp substrates, leading to lower intra cellular drug concentrations and a poor prognosis. Such an association with the CC genotype was not observed in AML. In conclusion, these results suggested that the MDR1 TT genotype might influence risk of development of acute lympoblastic leukemia and the CC genotype might be linked to a poor prognosis of ALL.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Genes MDR/genética , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Subfamilia B de Transportador de Casetes de Unión a ATP , Adolescente , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Niño , Femenino , Frecuencia de los Genes , Genotipo , Humanos , India/epidemiología , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
CYP3A5 is a member of the CYP3A gene family which metabolizes 50% of therapeutic drugs and steroid hormones. CYP3A5*3 and CYP3A5*6 polymorphisms exhibit inter-individual differences in CYP3A5 expression. The CYP3A5*3 allele (A6986G transition in intron 3) results in loss of CYP3A5 expression and the CYP3A5*6 allele (G14690A transition in exon 2, leading to the skipping of exon 7) is associated with lower CYP3A5 catalytic activity. The aim of the present study was to investigate their influence on susceptibility to chronic myeloid leukemia (CML). 265 CML cases and 241 age and sex matched healthy controls were analyzed by the PCR-RFLP technique. The frequencies of homozygous 3/3 genotype and CYP3A5*3 allele were elevated significantly in the CML group compared to controls (χ²=93.15, df=2, p=0.0001). With respect to clinical parameters, CYP3A5*3 allele frequency was increased in patients with advanced phase of the disease (0.71) as compared to those in chronic phase (0.65). Patients without hematological response (minor/poor) had higher frequency of 3/3 genotype (54.54%) as compared to those with major hematological response (41.2%). CYP3A5*6 allele was not observed in cases as well as in controls. Our study suggests that the CYP3A5*3 gene polymorphism is significantly associated with the risk of CML development and disease progression.
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Citocromo P-450 CYP3A/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
The GSTP1 enzyme plays a key role in biotransformation and bioactivation of certain environmental pollutants such as benzo[a]pyrene-7, 8-diol-9,10-epoxide (BPDE) and other diol epoxides of polycyclic aromatic hydrocarbons. It catalyses the detoxification of base propanols that arise from DNA oxidation thus offering cellular protection against oxidative stress. A single nucleotide polymorphism at codon 105 results in the substitution of isoleucine (Ile) to valine (Val) causing a metabolically less active variant of the enzyme. We here assessed the impact of the GSTP1 codon 105 polymorphism in chronic myeloid leukemia (CML) development and therapy response. The Ile105Val polymorphism was analyzed using a PCR-RFLP technique. Two hundred and sixty patients with CML and 248 healthy, age and sex matched controls were included in the study of associations with patient characteristics and treatment outcome. The GSTP1 Ile105Val polymorphism was significantly associated with CML development (?2 = 9.57; df = 2; p = 0.0084). With respect to clinical phase, CML patients in advanced phase (accelerated and blast crisis) had higher frequency of heterozygous (Ile/Val) genotype (47.62%) compared to chronic phase (36.5%). Further 54.5% of patients in blast crisis carried valine allele as compared to those in chronic phase (36.5%). The frequency of combined genotypes (Ile/Val, Val/Val) was elevated in cytogenetic poor (41.6%) and minor (53.57%) responders as compared to major (38.51%) responders. Hence the present study suggests that GSTP1 Ile105Val polymorphism with reduced GSTP1 enzyme activity might influence CML development, progression and response rates.
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Gutatión-S-Transferasa pi/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Benzamidas , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Piperazinas/uso terapéutico , Reacción en Cadena de la Polimerasa , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
The human CYP17 gene, located on chromosome 10q24.3, plays a key role in sex steroid synthesis, mainly related to estrogen. A 5' UTR polymorphism involving a single base pair change in the promoter region results in increased transcriptional activity. In the present study of 250 breast cancer cases and 250 ma tched controls, the A1 genotype frequency was elevated in the disease group, while the A2 genotype frequency demonstrated no association. When data were stratified by risk conferring group, however, the A2 genotype frequency was increased in postmenopausal breast cancer cases (4.2%), patients positive for a family history of breast cancer (5.5%), high BMI, estrogen receptor (6.2%) and progesterone receptor negative (5.0%) status, HER2/neu positive (7.7%) status, positive node status (5.0%) as well as advanced stage of the disease. The A1A1 genotype linked with increased production of androgens might impact on onset of breast cancer while the A2 allele showed associations with respect to important risk conferring parameters.
Asunto(s)
Neoplasias de la Mama/genética , Mama/patología , Polimorfismo Genético/genética , Esteroide 17-alfa-Hidroxilasa/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , India , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: The Cytochrome P-4501A1 (CYP1A1) gene, located on chromosome 15q, is involved in the metabolism of carcinogens mainly polycyclic aromatic hydrocarbons as well as estrogen. It is considered as candidate gene for low-penetrance breast cancer susceptibility. Hence the present study aims to discuss the role of CYP1A1 polymorphisms in breast cancer. MATERIALS AND METHODS: A total of 250 breast cancer patients and the same number of healthy age-matched controls were analyzed for the polymorphism of CYP1A1*2 by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In the present study, association of CYP1A1*2 (Ile 462Val) polymorphism with breast cancer was studied. Only one breast cancer patient was observed to be homozygous for Val allele but none among controls. The frequency of heterozygous Ile/Val genotype was found to be increased significantly in breast cancer patients (68.1%) as compared to controls (51.0%). Higher frequency of heterozygotes for Val allele was observed among premenopausal breast cancer patients and patients with high BMI, positive for HER2/neu status and advanced stage of the disease in comparison to the corresponding groups. No significant association of CYP1A1*2 polymorphism was observed with occupation, estrogen receptor and progesterone receptor status of breast cancer patients. CONCLUSIONS: In conclusion, our results suggest a significant correlation between CYP1A1*2 expression and the occurrence of breast cancer.