RESUMO
INTRODUCTION: Ten viral genotypes (A-J) distributed in all continents have been described for hepatitis B virus (HBV). One of the methodologies for determining the viral genotype is the restriction fragment length polymorphism (RFLP) technique, a simple and relatively inexpensive method, albeit with some limitations. OBJECTIVE: The initial objective of the project was to identify the HBV genotypes by RFLP in serum samples obtained from patients and blood donors. However, due to the discrepancies of RFLP patterns it was also necessary to perform phylogenetic genotyping and in silico analysis of HBV sequences. MATERIALS AND METHODS: We obtained 56 serum samples. DNA extraction was followed by PCR amplification of a fragment of HBV ORF S. We analyzed PCR products by RFLP with AlwI, BsrI, CfrI, HpaII and StyI, and we sequenced some. We compared the patterns obtained with those in previous reports. We also performed RFLP analysis in silico since we found differences between the patterns expected and those obtainedResults: We identified genotypes A and F, subgenotype F3, in the samples. This result is in agreement with those of previous studies carried out in Colombia; indeed, subgenotype F3 is the most frequent in the Andean region of the country, while genotype A is the most frequent HBV genotype in the western region (department of Chocó). Based on the in silico analysis of 229 HBV sequences from GenBank and 11 sequences of this study, we identified the RLFP pattern for genotype F, subgenotype F3, and we described some modifications of genotype A RFLP patterns. CONCLUSIONS: We identified the single nucleotide polymorphism pattern for genotype F, subgenotype F3, by in silico analysis and sequencing. Further robust in silico analyses are necessary to validate the RFLP patterns of HBV genotype and subgenotypes.
Assuntos
DNA Viral/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Polimorfismo de Fragmento de Restrição/genética , Colômbia/epidemiologia , DNA Viral/química , Genótipo , Humanos , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Matrix metalloproteinase 9 (MMP9) plays a critical role in cancer aggression, and its overexpression is associated with a poor prognosis in breast cancer. Because common genetic variants can alter the expression or function of MMPs, we hypothesized that potentially functional single-nucleotide polymorphisms (SNPs) in the MMP9 gene may be associated with the survival of patients with invasive breast cancer. In this case-cohort follow-up study, a total of 245 breast cancer patients in southeast China were investigated, and five haplotype tagging SNPs (htSNPs) in the MMP9 gene were genotyped by using matrix-assisted laser desorption/ionization mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism methods. Disease-free survival (DFS) and distance disease-free survival (DDFS) analyses were used to identify the SNPs associated with prognosis and determine their interdependence with the recognized prognostic factors. We found that the MMP9 rs3787268 GA+AA genotypes were significantly associated with poor DFS and DDFS of patients with breast cancer (log-rank p-values 0.045 and 0.028, respectively), especially in some subgroups of patients. Multivariate Cox regression and stepwise COX regression analyses suggested that rs3787268 may be a candidate independent biomarker to predict breast cancer survival in this population. Further, among estrogen receptor (ER)+/epidermal growth receptor 2 (HER-2)- patients, the rs3787268 GA+AA genotypes and rs17577 GG genotype showed a locus-dosage effect between combined the genotypes and decreased survival (adjusted HR 2.59, 95% confidence interval [CI] 1.29-5.19 and adjusted HR 3.25, 95% CI 1.39-7.58, respectively, for DFS and DDFS). Our results suggest that the polymorphisms in the MMP9 gene may be genetic modifiers for breast cancer prognosis in this Chinese population.
Assuntos
Povo Asiático/genética , Neoplasias da Mama/mortalidade , Carcinoma/mortalidade , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/estatística & dados numéricos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Carcinoma/diagnóstico , Carcinoma/etnologia , Carcinoma/genética , China/epidemiologia , Feminino , Genes Modificadores/fisiologia , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , População , Prognóstico , Análise de SobrevidaRESUMO
To investigate the association of survivin -31G/C, -141G/C, and -241T/C polymorphisms with colorectal cancer (CRC) susceptibility and explore the mechanisms of the survivin polymorphism in CRC development. A case-control study was conducted of 275 CRC cases and 270 healthy controls. Polymorphisms of survivin -31G/C, -141G/C, and -241T/C were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Survivin and Ki-67 expression was analyzed by immunohistochemistry by the Envision technique for the paraffin sections of 152 CRC. It showed that the -31G/C genotype and allele distribution were significantly different between the CRC cases and controls. The -31CC genotype and -31C allele were over-represented among the CRC cases. Compared with the CC genotype, the GC and GG genotypes had a significantly decreased risk of CRC (p=0.015). Survivin and Ki-67 expression of patients with the CC genotype was significantly higher than the patients with the GC and GG genotypes. In addition, a significantly positive correlation was found between expression of Survivin and Ki-67. There were no significant difference of the -141G/C and -241T/C polymorphism distributions among cases and controls. Survivin 31G/C may adjust the Survivin expression, and it might contribute to a risk of developing CRC.
Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Carcinoma/epidemiologia , Carcinoma/etnologia , Carcinoma/metabolismo , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , População , SurvivinaRESUMO
Serum paraoxonase (PON1) is an esterase that is involved in the detoxification of organophosphate insecticides. Emerging lines of evidence have shown that functional polymorphisms in the PON1 gene might play a critical role in increasing susceptibility to organophosphate toxicity, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between the PON1 polymorphisms and organophosphate toxicity risk. Nine case-control studies were assessed with a total 1,042 patients with organophosphate toxicity and 1014 healthy controls. The meta-analysis results showed that the PON1 192Q and 55L polymorphisms may increase the risk of organophosphate toxicity. Further subgroup analyses by ethnicity showed significant associations of the PON1 192Q and 55L polymorphisms with increased risk of organophosphate toxicity among the Caucasian populations. However, similar associations were not observed among the Asian populations. In conclusion, the current meta-analysis indicates that the PON1 192Q and 55LM polymorphisms may increase the risk of organophosphate toxicity, especially among the Caucasian populations.
Assuntos
Arildialquilfosfatase/genética , Intoxicação por Organofosfatos/genética , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos/genética , Substituição de Aminoácidos/fisiologia , Arginina/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Ácido Glutâmico/genética , Humanos , Leucina/genética , Metionina/genética , Intoxicação por Organofosfatos/epidemiologia , Intoxicação por Organofosfatos/etnologia , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , População Branca/genética , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Interleukin-6 (IL-6) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases such as coronary artery disease (CAD). The -174 IL-6 G/C promoter polymorphism influences mRNA levels and protein expression and is implicated in CAD. The Indian population in South Africa, unlike the black community, has a high prevalence of premature CAD. This polymorphism has not been fully explored in this population. The present study assessed the -174 IL-6 G/C polymorphism in young Indian patients with angiographically documented CAD and compared them with age- and gender-matched Indian and black control subjects. METHODS: Polymorphic variants were assessed by polymerase chain reaction-restriction fragment length polymorphism, and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The -174 IL-6 C allele was found with a higher frequency (23%) in the total Indian group compared to 2% in the black participants [P<0.0001, odds ratio (OR)=0.05, 95% confidence interval (CI) 0.018-0.14). The difference in frequency was more pronounced when Indian controls were compared to black controls (29% vs. 2%, respectively) (P<0.0001, OR=0.05, 95% CI 0.02-0.17). A significant association between the -174 IL-6 G allele and CAD was found in Indian patients compared to Indian controls (84% in cases vs. 71% in Indian controls; P=0.043, OR=0.47 95% CI 0.23-0.95). Levels of IL-6 in circulation were higher in black controls (6.62±0.63 pg/mL) compared to Indian controls (2.51±0.57 pg/mL) and CAD patients (1.46±0.36 pg/mL) (P<0.0001). Levels of IL-6 were higher in all groups with homozygous -174 IL-6 C alleles, but only significant in the healthy Indian control group (GG 3.73±0.94 pg/mL vs. GC/CC 0.89±0.5 pg/mL, P=0.0001). CONCLUSION: The presence of the IL-6 -174 G allele influences levels of IL-6 and increases the risk of CAD in South African Indians.
Assuntos
Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idade de Início , População Negra/etnologia , População Negra/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Prevalência , Regiões Promotoras Genéticas/genética , Fatores de Risco , África do Sul/epidemiologia , Adulto JovemRESUMO
Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid ß-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.
Assuntos
Doença de Gaucher/diagnóstico , Doença de Gaucher/genética , Técnicas de Diagnóstico Molecular , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Análise Mutacional de DNA/métodos , Feminino , Doença de Gaucher/complicações , Doença de Gaucher/epidemiologia , Predisposição Genética para Doença , Genótipo , Glucosilceramidase/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição/fisiologia , Tunísia/epidemiologia , Adulto JovemRESUMO
Insulin-like growth factor 2 (IGF2) gene has an important role in fetal growth. It was investigated association of the IGF2/ApaI polymorphism with low birth weight and normal birth weight (as control) in children attended in Hospital Dom Malan Petrolina, PE-Brazil. The genotype frequencies did not differ statistically between low birth weight (AA = 16.22%, AG = 43.24%, GG = 40.54%) and control (AA = 20% AG = 35%, GG= 45% groups) and the allele frequencies were not significantly different (p > 0.05).The observed genotype frequencies in both groups did not deviate significantly from Hardy-Weinberg equilibrium. Then, no significant correlation was found for this polymorphism in the population studied.
Assuntos
Peso ao Nascer/genética , Fator de Crescimento Insulin-Like II/genética , Polimorfismo de Fragmento de Restrição/fisiologia , Brasil , Estudos de Casos e Controles , Criança , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Feminino , Frequência do Gene , Estudos de Associação Genética , Geografia , Humanos , Recém-Nascido , Fator de Crescimento Insulin-Like II/metabolismo , Polimorfismo de Fragmento de Restrição/genética , GravidezRESUMO
Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)(2) D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35 d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n = 56) than in controls (n = 46) [mean (95%CI) = 78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p = 0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)(2) D [median (IQR) = 89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p = 0.03], or children with established diabetes [137 (113-153) pmol/L, p = 0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Vitamina D/sangue , Adolescente , Austrália/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Feminino , Humanos , Masculino , Hormônio Paratireóideo/sangue , Polimorfismo de Fragmento de Restrição/fisiologia , Receptores de Calcitriol/genética , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/genéticaRESUMO
Phagocytic NADH/NADPH oxidase is an important enzyme producing reactive oxygen species within subendothelial space of vessels. Findings have shown that p22phox subunit is an essential element related to the enzyme activity. Since some p22phox polymorphisms are thought to have functional roles in the enzyme thus, we studied the association between rs4673 (C242T) and rs13306294 (A/G) haplotypes and the severity of stenosis in coronary arteries. One hundred eighty-two subjects undergoing coronary angiography were recruited on the base of study design. Patients (n=114) had at least a stenosed coronary artery (>50% stenosis) and subdivided into three subgroups; SVD (n=28), 2VD (n=31) and 3VD (n=55) while controls (n=68) had the normal coronary arteries (<5% stenosis). The direct haplotyping technique of SNPs was performed using ARMS-RFLP-PCR method. Furthermore, alphabet-based tools predicted the changes of secondary structure at the rs4673 position. All haplotypes being proposed theoretically were found in the study population. The distribution of two-allele haplotypes had no significant difference between patients and controls (P=0.1). Although the rs4673 allele frequency was not significant between the groups (P>0.5), chi square test and multinomial regression analysis showed an observed high risk for rs13306294 A allele among patients. The bioinformatics tools predicted that the p22phox secondary structure is not changed due to the substitution of TyrâHis at the rs4673 position. We concluded that the polymorphisms have no allele linkage on the chromosome. In addition, the rs13306294 A allele is a potential factor of stenosis of coronary arteries that increases susceptibility for the extent of disease.
Assuntos
Estenose Coronária/genética , NADPH Oxidases/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Sequência de Bases , Estudos de Casos e Controles , Estenose Coronária/diagnóstico , Estenose Coronária/patologia , Feminino , Frequência do Gene , Ligação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Índice de Gravidade de DoençaRESUMO
Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. The results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.
Assuntos
Proteína C-Reativa/metabolismo , Creatina Quinase Forma MM/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Exercício Físico/fisiologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Adolescente , Adulto , Atletas , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Fatores de Risco , Adulto JovemRESUMO
SETTING: Antituberculosis drug-induced hepatitis attributed to isoniazide (INH) is one of the most prevalent drug-induced liver injuries. INH is metabolized by hepatic N-acetyltransferase 2 (NAT2) to form hepatotoxins. AIM: To evaluate whether polymorphism of the NAT2 gene was associated with antituberculosis drug-induced hepatotoxicity in Tunisian patients. METHODS: A total of 66 patients with tuberculosis (TB) who received anti-TB treatment were followed prospectively. Their NAT2 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We identified three single nucleotide polymorphisms (SNPs); 481C to T (NAT2*5B), 590G to A (NAT2*6A) and 857G to A (NAT2*7B). Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. RESULTS: Fourteen patients (21.2%) were diagnosed with anti-TB drug-induced hepatitis. None of the rapid acetylators-type patients have expressed serum aminotransferase elevation. Among patients with hepatotoxicity, slow acetylators-type patients had a higher risk of hepatotoxicity than intermediate acetylators (21.4% vs. 78.6%, P=0.01). Statistical analysis revealed that the frequency of a variant diplotypes, NAT2*5B/5B and NAT2*6A/6A, were significantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity (P=0.01, odds ratio [OR]=7.6 and P=0.029, OR=15, respectively). By contrast, the frequency of the rapid acetylation NAT2*4 allele was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P=0.02, OR=0.18). Moreover, 590G/G genotype was associated with decreased hepatotoxicity (P=0.01); by contrast, homozygous point mutation at position 481 and 590 were associated with a higher risk of hepatotoxicity (P=0.01). CONCLUSION: Our results suggest that the slow-acetylator status of NAT2 is risk factor for INH-induced hepatotoxicity. Moreover, diplotypes, NAT2*5B/5B, NAT2*6A/6A, 481T/T and 590A/A, are useful new biomarkers for predicting anti-TB drug-induced hepatotoxicity.
Assuntos
Antituberculosos/efeitos adversos , Arilamina N-Acetiltransferase/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/tratamento farmacológico , Adulto , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , Tuberculose/epidemiologia , Tuberculose/genética , Tunísia/epidemiologia , Adulto JovemRESUMO
Vascular endothelial growth factor (VEGF) is known to be a key molecule in the pathogenesis of endometriosis. In this study, we evaluated whether two polymorphisms -460T>C and +405G>C in VEGF are related with the susceptibility to endometriosis in northern Iran. Genomic DNA derived from patients with endometriosis and healthy women were analysed by polymerase chain reaction-restriction fragment length polymorphism. The total number of 1080 subjects (480 patients with endometriosis and 600 normal controls) was enrolled into the study. We used the Chi-square (χ(2)) test to evaluate each allele and genotype frequency of -460T>C and +405G>C polymorphisms among the cases and controls. The associations between the polymorphisms and the risk of endometriosis were estimated by odds ratio and their 95% confidence intervals. There was no significant differences in the VEGF -460T>C genotypes and allele frequencies between control women and endometriosis patients (P = 0.63). In contrast, an increased frequency of the +405CC genotype was observed in the patients with endometriosis as compared with the controls. The +405C allele was associated with the presence of endometriosis. It is concluded that the +405G>C polymorphism in VEGF may be associated with higher risk of endometriosis in northern Iran.
Assuntos
Endometriose/genética , Doenças Peritoneais/genética , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos de Casos e Controles , Endometriose/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Doenças Peritoneais/epidemiologia , Polimorfismo Genético/fisiologia , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , Adulto JovemRESUMO
Within an allostatic load framework, the effect of Gene × Environment (G × E) interactions on diurnal cortisol regulation and internalizing symptomatology were investigated. Variation in the corticotropin releasing hormone receptor 1 (CRHR1) TAT haplotype and serotonin transporter linked polymorphic region (5-HTTLPR) was determined in a sample of maltreated (n = 238, 21.4% with early physical and sexual abuse) and nonmaltreated (n = 255) children (M age = 10.08) participating in a summer research camp. Internalizing and depressive symptoms were assessed by other and self-report. G × E effects for CRHR1 and maltreatment and early abuse on diurnal cortisol regulation were observed; CRHR1 variation was related to cortisol dysregulation only among maltreated children. Early abuse and high internalizing symptoms also interacted to predict atypical diurnal cortisol regulation. The interaction of CRHR1, 5-HTTLPR, and child maltreatment (G × G × E) identified a subgroup of maltreated children with high internalizing symptoms who shared the same combination of the two genes. The findings support an allostatic load perspective on the effects of the chronic stress associated with child maltreatment on cortisol regulation and internalizing symptomatology as moderated by genetic variation.
Assuntos
Maus-Tratos Infantis , Depressão/etiologia , Hidrocortisona/fisiologia , Polimorfismo Genético/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Criança , Maus-Tratos Infantis/psicologia , Ritmo Circadiano/fisiologia , Depressão/genética , Depressão/fisiopatologia , Feminino , Interação Gene-Ambiente , Estudos de Associação Genética , Haplótipos/genética , Haplótipos/fisiologia , Humanos , Hidrocortisona/análise , Masculino , Polimorfismo Genético/fisiologia , Polimorfismo de Fragmento de Restrição/genética , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Escalas de Graduação Psiquiátrica , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Saliva/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/fisiologiaRESUMO
BACKGROUND: Adiponectin is a plasma protein produced by the adipose tissue, with insulin sensibility, antiinflammatory and antiatherogenic properties. Many adiponectin gene polymorphisms have been described, and their implication in obesity, metabolic syndrome, and cardiovascular diseases was controversial. Our aim was to study the relationship between eight adiponectin polymorphisms (-1391G/A, -1377C/G, 4522C/T, 395 G/A, 276G/T, 639C/T, 45T/G, and +2019delA), metabolic syndrome parameters, and the risk of obesity in Tunisian volunteers. METHODS: We have recruited 169 nonobese [sex ratio=0.594, mean age 43.25±13.12 years; mean body mass index (BMI) 24.73±3.50 kg/m(2)] and 160 obese (BMI≥30 kg/m(2)) (sex ratio=0.221, mean age 48.41±10.92 years; mean BMI 36.6±4.8 kg/m(2)). Genotyping was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Glucose, insulin, and lipids were measured. BMI and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS: The polymorphisms 276G/T, 639 C/T, 11391 G/A, 11374C/G, and +2019delA seem to contribute to obesity. In fact, adjusted odds ratios (ORs) of obesity associated with mutated genotypes of each polymorphism were, respectively: OR=0.64, P=0.039; OR=1.85, P=0.018; OR=1.68, P=0.044; OR=1.77, P=0.038; and OR=1.94, P=0.010). Mutated genotypes at 639 C/T were associated with higher waist circumference, BMI, and systolic and diastolic blood pressure. In addition, the 11391AA genotype was associated with increased BMI. Concerning 2019delA, the delAdelA genotype was associated with increased HOMA-IR and BMI, suggesting a possible effect of these single-nucleotide polymorphisms (SNPs) on insulin resistance parameters. Mutated genotypes at 276G/T were associated with lower serum insulin concentration and lower systolic and diastolic blood pressure. The other genotypes showed no association with metabolic syndrome parameters. CONCLUSION: Adiponectin gene polymorphisms were associated with obesity and metabolic syndrome parameters in Tunisian volunteers.
Assuntos
Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo Genético/fisiologia , Adiponectina/genética , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Experimentação Humana , Humanos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , Deleção de Sequência/fisiologia , TunísiaRESUMO
The aim of the study is evaluating the associations of FokI vitamin D receptor (VDR) gene polymorphisms with gestational diabetes mellitus (GDM), and its relations with postpartum metabolic syndrome. In a cohort study, 303 women referred to outpatient clinic of Shariati Hospital. The VDR FokI genotypes were determined. All subjects were followed 6?12 weeks after delivery. The frequencies of Ff, FF, and ff genotypes were 30.4% (49), 63.4% (102), and 6.2% (10), respectively, in healthy pregnancies and 34.5% (49), 54.9% (78), and 10.6% (15), respectively, in GDM patients. The ff genotype was more common in GDM patients. Healthy individuals had higher frequency of F allele, suggesting that F allele may have a role in decreased incidence of GDM. Concerning the GDM risk factors, f allele had significant association with prepregnancy obesity and family history of diabetes. In postpartum follow-up, women who developed metabolic syndrome were significantly older with higher prepregnancy body mass index, had more family history of diabetes, and also their ff genotype was two fold more frequent. Our results indicate a meaningful association between FokI VDR genotypes and an increase risk of GDM in Iranian population as well as its effects on postpartum metabolic syndrome.
Assuntos
Diabetes Gestacional/genética , Polimorfismo de Fragmento de Restrição/fisiologia , Complicações na Gravidez/genética , Receptores de Calcitriol/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Diabetes Gestacional/etiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Irã (Geográfico) , Período Pós-Parto/genética , Gravidez , Complicações na Gravidez/etiologia , Receptores de Calcitriol/metabolismo , Fatores de Risco , Adulto JovemRESUMO
The cytochrome P-450 1A1 (CYPA1A) gene plays an important role in the metabolization of estrogen and is therefore a candidate marker for fibroids. In a case-control study, we were unable to demonstrate any association between MSP I CYP1A1 polymorphism and the risk of leiomyoma in Brazilian women.
Assuntos
Citocromo P-450 CYP1A1/genética , Desoxirribonuclease HpaII , Leiomioma/genética , Polimorfismo de Fragmento de Restrição/fisiologia , Neoplasias Uterinas/genética , Adulto , Brasil , Estudos de Casos e Controles , Citocromo P-450 CYP1A1/fisiologia , Desoxirribonuclease HpaII/metabolismo , Estradiol/sangue , Estradiol/farmacocinética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Leiomioma/sangue , Leiomioma/metabolismo , Taxa de Depuração Metabólica/genética , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Fatores de Risco , Neoplasias Uterinas/sangue , Neoplasias Uterinas/metabolismoRESUMO
OBJECTIVE: The purpose of this study was the correlation of the combined type of ADHD in children and Taq IA polymorphism DRD2 gene. We hypothesized a positive correlation of DRD2 polymorphisms in the combined type of ADHD patients without co-morbidity. PATIENTS AND METHODS: Our research sample included 586 unrelated boys of the Czech origin aged between 6 and 13 years. The ADHD group consisted of 269 boys and the control group consisted of 317 boys. PCR detection of the DRD2 polymorphism was carried out by using primers, described by Grandy (Grandy et al. 1989). RESULTS: The comparison of genotype frequencies showed statistically highly significant difference between the studied groups (p<0.0001). A statistically significant difference was also found when the allelic frequencies between the two groups were compared (p<0.0001), with the A1 allele having a 4.359 fold higher risk of ADHD (Risk Ratio=4.359, 95% CI of RR=3.5753 to 5.3144, Odds Ratio= 7.7824; 95% CI of OR=10.315 to 13.6719). CONCLUSIONS: Our results presented a highly positive correlation between the combined type of ADHD without co-morbidity and ANKK l (DRD2) polymorphism .
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Polimorfismo de Fragmento de Restrição , Receptores de Dopamina D2/genética , Receptores Dopaminérgicos/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , República Tcheca/epidemiologia , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Fragmento de Restrição/fisiologia , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Leptin and adiponectin are cytokines produced by adipose tissue with opposite effects on tumor growth: the former stimulate whereas the latter inhibit it. The objective was to analyze the association of LEP A19G and ADIPOQ+45 T/G and +276 G/T polymorphisms in Mexican patients with colorectal cancer (CRC). 68 unrelated patients with CRC (study group) and 102 blood donors (control group); all subjects were Mestizos from western Mexico. The polymorphisms were established by PCR-RFLP on DNA samples obtained from peripheral blood. The LEP A19G polymorphism showed significant differences between CRC patients and control group (p= 0.01 for G/A genotype and p= 0.02 for the recessive model G/G +G/A); yet, in the analysis stratified by gender, this difference remained significant only in males. The ADIPOQ polymorphisms did not shown any significant differences. Our results suggest that the A19G LEP polymorphism is associated with CRC in Mexican patients.
Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Leptina/genética , Adiponectina/genética , Carcinoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Feminino , Frequência do Gene , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Associations between the TAQIB and I405V polymorphisms and obesity risk were studied for a single locus as well as in combination. A total of 934 obese subjects and 924 normal controls were included in the study. TAQIB was associated with high-density lipoprotein (HDL) levels (P < 0.001), while I405V was associated with levels of low-density lipoprotein (P = 0.03) and total cholesterol (P = 0.007). Less common alleles of TAQIB and I405V were associated with decreased obesity risk and further drops in odds ratio (OR) were observed in carriers with rare homozygous alleles on both loci (OR = 0.659, P = 0.02). The TAQIB B2 allele was associated with reductions in both hip circumference (P = 0.034) and triceps skinfold thickness (TST) (P = 0.045), although this effect was completely abolished after controlling for HDL levels. The 405V variant was associated with reductions in hip circumference (P = 0.031), body fat composition (P = 0.039) and TST (P = 0.036); these effects were weakened (P < 0.1) after controlling for HDL levels. In conclusion, less common alleles of TAQIB and I405V appear to be modestly associated with obesity risk in an adult Chinese population. Adjustments for HDL levels completely (TAQIB) or partially (I405V) abolished the observed association.
Assuntos
Povo Asiático/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Obesidade/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Adulto , Substituição de Aminoácidos/genética , Estudos de Casos e Controles , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Feminino , Predisposição Genética para Doença , Genética Populacional , Humanos , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Polimorfismo de Fragmento de Restrição/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Risco , Valina/genéticaRESUMO
Phylogenetic relationships and genome affinities were investigated by utilizing all the biological Avena species consisting of 11 diploid species (15 accessions), 8 tetraploid species (9 accessions) and 4 hexaploid species (5 accessions). Genomic DNA regions of As120a, avenin, and globulin were amplified by PCR. A total of 130 polymorphic fragments were detected out of 156 fragments generated by digesting the PCR-amplified fragments with 11 restriction enzymes. The number of fragments generated by PCR-amplification followed by digestion with restriction enzymes was almost the same as those among the three repeated DNA sequences. A high level of genetic distance was detected between A. damascena (Ad) and A. canariensis (Ac) genomes, which reflected their different morphology and reproductive isolation. The A. longiglumis (Al) and A. prostrata (Ap) genomes were closely related to the As genome group. The AB genome species formed a cluster with the AsAs genome artificial autotetraploid and the As genome diploids indicating near-autotetraploid origin. The A. macrostachya is an outbreeding autotetraploid closely related with the C genome diploid and the AC genome tetraploid species. The differences of genetic distances estimated from the repeated DNA sequence divergence among the Avena species were consistent with genome divergences and it was possible to compare the genetic intra- and inter-ploidy relationships produced by RFLPs. These results suggested that the PCR-mediated analysis of repeated DNA polymorphism can be used as a tool to examine genomic relationships of polyploidy species.