RESUMO
PURPOSE: Superoxide dismutase (SOD) is an enzyme that ensures detoxification against oxidative stress in extracellular components. We aimed to evaluate the impact of SOD3G362A polymorphism (rs 2536512) on the impairment of seminal SOD activity and its risk for idiopathic male infertility in Algeria, as well as to investigate the association between sperm DNA integrity, standard semen parameters, and seminal SOD activity. METHODS: In this case-control study, we included 111 infertile men with idiopathic infertility and 104 fertile controls from Algeria. Semen analyzing was done according to the World Health Organization manual. Seminal SOD activity was measured using a commercially colorimetric method (Randox Laboratories Ltd., UK). DNA fragmentation was evaluated using the Halosperm kit (Halotech DNA S.L, Spain) and SOD3G362A genotyping was assessed by polymerase chain reaction-restriction length fragment polymorphism (PCR-RFLP). RESULTS: Seminal SOD activity was significantly lower in the infertile group than in the control group (85.87±40.11 vs 154.24±48.456U/mL, p<0.0001), it also decreased in all infertile subgroups. We detected positive correlations between SOD activity and semen parameters (concentration, mobility, vitality, and morphology) (p≤0.05). There was no association between the risk for male infertility and DNA integrity (p>0.05) and SOD3G362A (OR=0.826, 95%CI: 0.439-1.55, p=0.554). For GA vs GG and (OR=0.639, 95% CI: 0.305-1.340, p=0.235) for AA vs GG. CONCLUSIONS: Seminal SOD evaluation can be a beneficial indicator for sperm quality and risk for idiopathic male infertility in Algeria, while sperm DNA integrity, as well as SOD3G362A genotypes, are not.
Assuntos
Infertilidade Masculina/genética , Sêmen/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Argélia , Estudos de Casos e Controles , DNA , Fragmentação do DNA , Humanos , Masculino , Polimorfismo Genético , Análise do SêmenRESUMO
Hydrochlorothiazide (HCTZ) belongs to the thiazide diuretics family that is used for the treatment of hypertension. Enalapril is another drug that is used for the treatment of hypertension. Recently, both drugs were combined in a single medication called vaseretic that showed a strong synergistic effect against hypertension. The aim of this investigation is to examine genotoxicity of HCTZ/enalapril on chromosomal damage by measuring the frequency of sister-chromatid exchanges (SCEs) in cultured human lymphocytes. Findings showed that HCTZ (5µg/mL) significantly increased SCEs frequency (P<0.01) in cultured cells relative to the untreated cells. The levels of SCEs induced by Enalapril (10µg/mL) was similar to the level detected in the untreated cultures (P>0.05). Interestingly, SCEs induced by combined treatment were significantly lower than HCTZ alone (P<0.05). Thus, enalapril seems to protect lymphocytes from genotoxicity induced by HCTZ. Neither HCTZ nor enalapril treatment (alone or in combination) induced changes in the mitotic index and the proliferative index (P>0.05). In conclusion, HCTZ increased SCEs in cultured lymphocytes, and this increase is reduced by enalapril.
Assuntos
Anti-Hipertensivos/uso terapêutico , Enalapril/farmacologia , Hidroclorotiazida/toxicidade , Linfócitos/efeitos dos fármacos , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/toxicidade , Cromossomos Humanos/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Enalapril/administração & dosagem , Enalapril/uso terapêutico , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/antagonistas & inibidores , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Masculino , Troca de Cromátide Irmã/efeitos dos fármacos , Adulto JovemRESUMO
Jordan, located in the Levant region, is an area crucial for the investigation of human migration between Africa and Eurasia. However, the genetic history of Jordanians has yet to be clarified, including the origin of the Bedouins today resident in Jordan. Here, we provide new genetic data on autosomal independent markers in two Jordanian population samples (Bedouins and the general population) to begin to examine the genetic diversity inside this country and to provide new information about the genetic position of these populations in the context of the Mediterranean and Middle East area. The markers analyzed were 18 Alu polymorphic insertions characterized by their identity by descent, known ancestral state (lack of insertion), and apparent selective neutrality. The results indicate significant genetic diffferences between Bedouins and general Jordanians (p = 0.038). Whereas Bedouins show a close genetic proximity to North Africans, general Jordanians appear genetically more similar to other Middle East populations. In general, these data are consistent with the hypothesis that Bedouins had an important role in the peopling of Jordan and constitute the original substrate of the current population. However, migration into Jordan in recent years likely has contributed to the diversity among current Jordanian population groups.
Assuntos
Elementos Alu , Árabes/genética , África do Norte , Feminino , Frequência do Gene , Deriva Genética , Marcadores Genéticos/genética , Variação Genética , Humanos , Jordânia , Masculino , Cadeias de Markov , Oriente Médio , Polimorfismo Genético , Migrantes/estatística & dados numéricosRESUMO
Folate pathway is expected to play an important role in spermatogenesis since it is involved in DNA synthesis, repair and methylation. The purpose of this study was to examine the association between male infertility and the MTHFR (C677T and A1298C) and MTRR (A66G) polymorphisms. A group of 300 males was recruited in this study from different Jordanian infertility clinics. Of these, 150 cases of infertile men that included oligozoospermia cases (n=45), severe oligozoospermia (n=71) and azoospermia (n=34) were studied. The other 150 males were age matched fertile controls. Genotyping of MTHFR and MTRR polymorphisms was performed using PCR-RFLP technique. The results showed an association between MTHFR 677TT genotype and male infertility (P<0.05). However, the distribution of MTHFR A1298C and MTRR A66G genotypes were not different between the fertile and infertile groups (P>0.05). In addition, none of the examined polymorphisms was related to any of the semen parameters in the infertile group. In conclusion, this study showed that MTHFR C677T polymorphism is associated with male infertility in Jordanians.
Assuntos
Ferredoxina-NADP Redutase/genética , Infertilidade Masculina/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Infertilidade Masculina/epidemiologia , Jordânia/epidemiologia , Masculino , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , População/genéticaRESUMO
The genotoxic effects of cigarette smoke filtrate (SF) on the germ-line stages were examined in Drosophila melanogaster using the sex-linked recessive lethal test, which detects a broad spectrum of genetic alterations and proved to show correlations between mutagenicity and carcinogenicity of the tested chemicals. SF was extracted from fiberglass filter cartridges; each used in smoking 15 cigarettes. The proper SF concentrations (0.2 µL) in 0.45% NaCl saline were injected intraperitoneally in 2- to 3-day-old wild-type males, alongside with controls injected with 0.2 µL of saline. The genotoxicity effects of SF were examined in all spermatogenesis stages of treated males. Results showed that SF was toxic with an median lethal dose value of approximately 0.2% and induced significant sterility effects. The mutagenicity of SF (0.2%) was significantly stage specific and induced complete sex-linked recessive lethal mutations in the broods representing the spermatocytes and late and early spermatogonia, and induced mosaic mutations in the untreated progeny in the brood representing late spermatogonia. These results indicated, for the first time, that SF induces mosaic mutations, which could result from DNA instabilities and labile permutations that can be replicated and passed to future generations before being fixed into mutations in the untreated progeny of treated males, or originating from mutations that result in increasing hyperplasia of the gonad that subsequently produce the actual mutations in later cell cycles. Such delayed mutagenic effects of SF indicated that SF and, consequently, cigarette smoking have much greater genotoxicity than what was previously predicted.
Assuntos
Genes Letais/efeitos dos fármacos , Genes Recessivos/efeitos dos fármacos , Mutagênicos/toxicidade , Fumaça/efeitos adversos , Animais , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Feminino , Células Germinativas/efeitos dos fármacos , Dose Letal Mediana , Masculino , Mosaicismo , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Cromossomos SexuaisRESUMO
OBJECTIVES: The aim of this study was to investigate the genotoxicity of waterpipe smoking in the lymphocytes of waterpipe smokers using chromosomal aberrations (CAs) assay. MATERIALS AND METHODS: Fifty waterpipe smokers and 18 healthy non-smokers volunteered to participate in the study. Additionally, 18 heavy cigarette smokers were recruited for comparison. Chromosomal aberrations (CAs) assay was used to evaluate DNA damage in the lymphocytes. RESULTS: The results showed that similarly to cigarette smoking, waterpipe smoking significantly increased the frequencies of CAs (p < 0.01). In addition, the frequencies of CAs increased with more waterpipe use. CONCLUSIONS: Waterpipe smoking causes DNA damage to lymphocytes and the damage increases with more waterpipe use.
Assuntos
Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA/genética , Linfócitos/efeitos dos fármacos , Fumar/efeitos adversos , Adulto , Humanos , Jordânia , Nicotiana/efeitos adversos , Adulto JovemRESUMO
AIM: Although much of Jordan is covered by desert, its north-western region forms part of the Fertile Crescent region that had given a rich past to Jordanians. This past, scarcely described by historians, is not yet clarified by sufficient genetic data. Thus in this paper we aim to determine the genetic differentiation of the Jordanian population and to discuss its origin. METHODS: A total of 150 unrelated healthy Jordanians were investigated for ten Alu insertion polymorphisms. Genetic relationships among populations were estimated by a principal component (PC) plot based on the analyses of the R-matrix software. RESULTS: Statistical analysis showed that the Jordanian population is not significantly different from the United Arab Emirates population or the North Africans. This observation, well represented in PC plot, suggests a common origin of these populations belonging respectively to ancient Mesopotamia, Arabia, and North Africa. CONCLUSION: Our results are compatible with ancient peoples' movements from Arabia to ancient Mesopotamia and North Africa as proposed by historians and supported by previous genetic results. The original genetic profile of the Jordanian population, very likely Arabian Semitic, has not been subject to significant change despite the succession of several civilizations.
Assuntos
Elementos Alu/genética , Variação Genética , Genética Populacional , Polimorfismo Genético/genética , Fluxo Gênico , Humanos , Jordânia , Mutagênese Insercional , Análise de Componente PrincipalRESUMO
BACKGROUND: Imerslund-Gräsbeck syndrome (IGS) was described just over 50 years ago by Olga Imerslund and Ralph Gräsbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl) due to bi-allelic mutations in either the cubilin gene (CUBN) or the human amnionless homolog (AMN). Mutations in the two genes are commonly seen in founder populations or in societies with a high degree of consanguineous marriages. One particular mutation in AMN, c.208-2A>G, causing an out-of-frame loss of exon 4 in the mRNA, is responsible for some 15% of IGS cases globally. We present evidence that this founder mutation causes a substantial percentage of cases among diverse ethnicities and that the mutation is as old as human civilization. METHODS: Partial genotyping indicated a founder event but its presence in diverse peoples of Arabic, Turkish, Jewish, and Hispanic ancestry suggested that the mutation might be recurrent. We therefore studied the flanking sequence spanning 3.5 Mb to elucidate the origin of the haplotype and estimate the age of the mutation using a Bayesian inference method based on observed linkage disequilibrium. RESULTS: The mutation's distribution, the size of the shared haplotype, and estimates of growth rate and carrier frequency indicated that the mutation was a single prehistoric event. Dating back to the ancient Middle East around 11,600 BC, the mutation predates the advent of writing, farming, and the monotheistic religions of the region. CONCLUSIONS: This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Efeito Fundador , Síndromes de Malabsorção/etnologia , Síndromes de Malabsorção/genética , Mutação , Proteínas/genética , Proteinúria/etnologia , Proteinúria/genética , Deficiência de Vitamina B 12/etnologia , Deficiência de Vitamina B 12/genética , Fatores Etários , Anemia Megaloblástica , Árabes/genética , Feminino , Genética Populacional , Humanos , Judeus/genética , Masculino , Proteínas de Membrana , Oriente MédioRESUMO
BACKGROUND: The activity of the methylenetetrahydrofolate reductase (MTHFR) enzyme is regulated by the two polymorphisms C677T and A1298C, which reduce enzyme activity and result in hypomethylation of chromosomes that increase the risk of nondisjunction. These polymorphisms are suggested to be risk factors for Down syndrome (DS) in some populations. AIM: The aim of this study was to test if C677T and A1298C polymorphisms are correlated to maternal risk of DS in Jordan. METHODS: The proportions of C677T and A1298C polymorphisms were examined in 53 case mothers who delivered DS children and 29 controls. The median age of case mothers was 35 years when delivering their affected children. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. RESULTS: The frequency of MTHFR C677T allele in all DS mothers was 3.2-fold higher than in the controls (odds ratio [OR] = 3.12, 95% confidence interval [CI]: 1.303-7.677). Also, the proportion of 677T in the older case mothers was different from the controls, but was significantly higher in younger case mothers than in the controls (OR = 4.2, 95% CI: 1.61-10.97, p = 0.003). The proportions of 677CT and 677TT genotypes in younger cases are, respectively, 10- and 9-fold higher than in the controls. The proportions of MTHFR A1298C are significantly different among all case groups and the controls (χ(2) = 4.27, p = 0.127), but there was a significant difference between young case mothers and both older case mothers group and the controls (OR = 1.25, 95% CI: 0.405-3.85, p = 0.698). CONCLUSIONS: There is strong association between MTHFRC677T and maternal risk of DS in Jordanian mothers younger than 35 years old and the MTHFR1298C allele has a lesser but additive risk effect in MTHFR677T/1298C compound heterozygotes.
Assuntos
Síndrome de Down/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Síndrome de Down/epidemiologia , Síndrome de Down/etnologia , Heterozigoto , Humanos , Jordânia , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Tobacco smoking is a major world health problem. Recently, waterpipe smoking has become more popular in many countries. Although the genotoxicity associated with cigarette smoking has been extensively investigated, studies evaluating such toxicity in waterpipe users are still lacking. In this study, we examined the genotoxicity of waterpipe smoking in lymphocytes compared with the genotoxicity of cigarette smoking. Genotoxicity was evaluated using the sister chromatid exchanges (SCEs) assay. Fifty waterpipe smokers and 18 healthy nonsmokers participated in this study. Additionally, 18 heavy cigarette smokers (CS) were recruited for comparison. The results show that waterpipe smoking and cigarette smoking significantly increase the frequencies of SCEs (P < 0.01) compared with those of nonsmokers, indicating the genotoxic effect of tobacco smoking. In addition, frequencies of SCEs were significantly higher among waterpipe smokers compared with CS (P < 0.01), indicating that waterpipe smoking is more genotoxic than cigarette smoking. Moreover, the frequency of SCEs increased with the extent of waterpipe use. In conclusion, waterpipe smoking is genotoxic to lymphocytes and the magnitude of its genotoxicity is higher than that induced by regular cigarette smoking.
Assuntos
Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Nicotiana/toxicidade , Troca de Cromátide Irmã/efeitos dos fármacos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Células Cultivadas , Humanos , Linfócitos/metabolismo , Testes de Mutagenicidade , Medição de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/análise , Adulto JovemRESUMO
The correlations between the presence of MTHFR 677 (C>T) and MTHFR 1298 (A>C) mutations in human lymphocytes and the sensitivity of lymphocytes to methotrexate (MTX) were examined in cultures derived from 82 unrelated women, genotyped for these mutations by polymerase chain reaction-restriction fragment length polymorphism. Lymphocytes heterozygous for the mutant allele, MTHFR 677T, were significantly more sensitive to methotrexate than those carrying the homozygous wild-type allele, MTHFR677C, and those carrying either the mutant or the wild-type alleles in the polymorphic MTHFR 1298 site. In addition, the lymphocyte cultures carrying the mutant MTHFR 1298C allele were not different in their sensitivity to MTX from those cultures carrying the wild-type allele, MTHFR 1298A. This demonstrated that the polymorphic site MTHFR C677, but not MTHFR1298, could be considered as a useful pharmacogenetic determinant in planning and designing the effective personal MTX chemotherapeutic doses and regimes.
Assuntos
Linfócitos/efeitos dos fármacos , Metotrexato/farmacologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Sensibilidade e Especificidade , Alelos , Antirreumáticos/farmacologia , Drogas Desenhadas/uso terapêutico , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Tratamento Farmacológico/métodos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Linfócitos/fisiologia , Mutação , Farmacogenética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Células Tumorais CultivadasRESUMO
The effects of trifluoperazine on the mutagenicity of cyclophosphamide were examined in the progenies of Drosophila melanogaster males injected with 2 microliters of 5.0 mM cyclophosphamide and/or 0.1 mM trifluoperazine. The Muller-5 method was used to study the induction of sex-linked recessive lethals in five successive broods representing the different stages of spermatogenesis. Results should that both cyclophosphamide and trifluoperazine were proportionally toxic to the injected males. While cyclophosphamide was less toxic than trifluoperazine, it increased the frequencies of induced complete and mosaic lethals significantly (5% level) in all stages of spermatogenesis contrary to trifluoperazine which was non mutagenic and had only an additive effect over the toxicity of cyclophosphamide. The sizes of the mutated gonad tissue in the F1 mosaic female progenies of the males treated with cyclophosphamide alone ranged from 14% to 17% and of those treated with cyclophosphamide in association with trifluoperazine varied between 18% and 19%. Both complete and mosaic sex-linked lethals induced by cyclophosphamide treatments alone and in association with trifluoperazine were detected in singles and clusters.