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1.
Wei Sheng Yan Jiu ; 48(4): 621-627, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31601346

RESUMO

OBJECTIVE: To investigate the effect of the interaction between methylenetetrahydrofolate reductase(MTHFR) genotype and allele and long-term exposure to organophosphorus pesticides on the development of type 2 diabetes mellitus(T2 DM). METHODS: A total of 209 cases of T2 DM(case group) and 216 cases without T2 DM(control group) were selected as subjects. The polymorphism of MTHFR(rs1801133) was detected by TaqMan probe technique. The relationship between genes, long-term exposure to organophosphorus pesticides and T2 DM was analyzed by Logistic regression. The interaction between gene and long-term exposure to organophosphorus pesticides was discussed by crossover analysis and generalized multifactor dimensionality reduction. RESULTS: BMI⇿4, residence in countryside, long-term exposure to organophosphorus pesticides and family history of diabetes mellitus were risk factors for T2 DM. MTHFR genotype distribution conformed to Hardy-Weinberg equilibrium(P>0. 05). There was no significant difference in genotype distribution frequency between case group and control group. The risk of T2 DM in individuals with CT and TT genotypes was 1. 667 times higher than that of CC genotypes after adjusting the covariates at rs1801133 locus in the dominant model(95%CI 1. 057-2. 627, P=0. 028). It suggested that the samples of allele T had a increased risk of T2 DM compared with those without allele T. The above models still had statistical significance(P<0. 05) after adjusting the covariates. Forth, crossover analysis showed that the gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides had multiplication interaction. The interaction between gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides may play a role in the pathogenesis of T2 DM. Generalized multifactor dimensionality reduction(GMDR)analysis showed that the interaction model of MTHFR(rs1801133) gene and family history of diabetes mellitus was the best model. CONCLUSION: MTHFR(rs1801133) gene CT and TT genotype may be risk factors for T2 DM. The interaction between genetic polymorphism and environmental factors increases the risk of T2 DM.


Assuntos
Diabetes Mellitus Tipo 2/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Compostos Organofosforados/toxicidade , Praguicidas/toxicidade , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
2.
Ann Hematol ; 98(10): 2257-2265, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31440871

RESUMO

Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation' and hemato-biochemical parameters in SCA and their effect on the vaso-occlusive crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher (p < 0.0001) in patients with SCA (22.41 ± 7.8 µmol/L) compared to controls (13.2 ± 4.4 µmol/L). Moreover, patients without FA supplementation had a significantly (p < 0.001) higher Hcy level (27 ± 7 µmol/L) compared to those with supplementation (17.75 ± 5.7 µmol/L). Turkey-Kramer multiple comparison tests show that there is a significant difference (p < 0.05) in HbF percent, hemoglobin (Hb), platelet count, serum bilirubin (direct:Bil-D and total:Bil-T), aspartate transaminase (AST), lactate dehydrogenase (LDH), and plasma Hcy levels between mild and severe VOC. Between moderate VOC and severe VOC, there was a significant difference (p < 0.05) in HbF%, Bil-D, AST, Hcy. Pearson correlation revealed that plasma Hcy had a significantly (p < 0.05) positive correlation with AST, serum bilirubin (indirect and total), LDH, jaundice, stroke, VOC per year, and hospitalization per year whereas it was inversely correlated with HbF percentage, Hb level, and FA treatment. In the study population, increased plasma Hcy level, hemolysis, and platelet activation were found to influence VOC in SCA.


Assuntos
Anemia Falciforme , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Doenças Vasculares , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/genética , Anemia Falciforme/fisiopatologia , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Plaquetas/metabolismo , Feminino , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , Hemólise , Homocisteína/genética , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/sangue , Pessoa de Meia-Idade , Ativação Plaquetária , Contagem de Plaquetas , Doenças Vasculares/sangue , Doenças Vasculares/etiologia , Doenças Vasculares/genética , Doenças Vasculares/fisiopatologia
3.
Gene ; 719: 144079, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31454542

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as a complex disorder. The etiology of PCOS is multifactorial with a clear genetic component. Several human studies have been conducted to explore the association between MTHFR polymorphisms and PCOS susceptibility, but these provide inconsistent results and the combined result of A1298C remains vacant. Our aim is to examine whether MTHFR C677T or A1298C are related to PCOS. METHODS: We conducted a meta-analysis to investigate the association between MTHFR C677T or A1298C polymorphisms and PCOS. Electronic database was searched, including PubMed, Embase, CNKI, Web of science and the reference lists of relevant articles for studies published from the inception to June 17, 2019. The included studies were assessed in the following genetic model: dominant model, recessive model, allelic model, homozygote model, Heterozygote model. RESULTS: 19 articles (21 studies) with 2383 patients of PCOS and 2492 controls were considered for MTHFR C677T, and 7 articles (8 studies) were employed for MTHFT A1298C in this meta-analysis. For MTHFR C677T and A1298C, significant association with PCOS was observed in the combined population and Asian population. None of the contrasts of genetic model yielded a significant finding in the Caucasian population. CONCLUSION: Our result based on previously published studies demonstrated that T allele in MTHFR C677T polymorphism might be a genetic risk factor for PCOS, especially in the Asian population. MTHFR A1298C might be contribute to PCOS susceptibility. More efforts and further studies with larger sample size will be required to validate the risk of PCOS.


Assuntos
Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Alelos , Feminino , Humanos
4.
Georgian Med News ; (290): 124-127, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322528

RESUMO

Autism spectrum disorders (ASD) are considered an epidemic - only in the last 5 years the incidence of pathology has increased from 1: 166 to 1:68 children. The main role in the pathogenesis of ASD currently belongs to the violation of the epigenetic status in the form of gene polymorphisms. An example is the polymorphic variants of the genes of the folate-methionine cycle enzymes, which regulate the epigenetic status through a methylation process. The article presents a case of autism spectrum disorder against the background of impaired epigenetic status (metabolic dopamine neurotransmitters and the methylation cycle). Individually selected metabolic correction based on biochemical parameters allowed improving behavior, stimulating speech development, stopping long subfebrile and hypersalivation.


Assuntos
Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/reabilitação , Epigênese Genética/genética , Ferredoxina-NADP Redutase/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Transtorno Autístico , Criança , Metilação de DNA , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2
5.
Rom J Ophthalmol ; 63(2): 107-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334388

RESUMO

Aim: Several epidemiological studies have been performed to explore the association of MTHFR polymorphisms with glaucoma risk. However, the results were inconsistent or even inconclusive. Hence, we performed a meta-analysis to evaluate the association of MTHFR C677T and A1298C polymorphisms with glaucoma risk. Methods: A comprehensive literature search on PubMed, Google Scholar, EMBASE, and CNKI databases was performed to find all eligible studies up to January 30, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. Results: A total of 42 case-control studies including 33 studies for MTHFR C677T and nine studies for A1298C polymorphism were selected. Pooled results showed that there was no significant association between the MTHFR C677T polymorphism and glaucoma risk. Similarly, no associations were found in subgroup analysis based on ethnicity and glaucoma type. However, there was a significant association between the A1298C polymorphism and the increased risk of glaucoma under heterozygote model (OR=0.765, 95% CI=0.626-0.935, P=0.009). Moreover, the significant association between MTHFR A1298C polymorphism and glaucoma were found by ethnicity and primary open angle glaucoma (POAG). Conclusions: The present meta-analysis revealed that MTHFR A1298C polymorphism is significantly associated with the increased risk of glaucoma, but not MTHFR C677T polymorphism.


Assuntos
DNA/genética , Glaucoma/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Estudos de Casos e Controles , Genótipo , Glaucoma/metabolismo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Medição de Risco
6.
BMC Med Genet ; 20(1): 94, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146742

RESUMO

BACKGROUND: There are several studies with inconsistent conclusions regarding the association between the rs1801133 and rs1801131 polymorphisms within the MTHFR (methylenetetrahydrofolate reductase) gene and colorectal polyp risk. This discrepancy led us to assess the genetic impact of the two polymorphisms on the susceptibility to colorectal polyps. METHODS: A meta-analysis was carried out for quantitative synthesis. According to the inclusion/exclusion criteria, we retrieved, screened and selected all published articles related to colorectal polyps and the MTHFR rs1801133 and rs1801131 polymorphisms. The P value of association test, RRs (risk ratios) and 95% CIs (confidence intervals) were mainly produced. RESULTS: A total of twenty-three case-control studies were included from twenty-two eligible articles. Pooling the results of both rs1801133 and rs1801131 polymorphisms in the overall population suggested a nonsignificant association between colorectal polyp cases and controls, in that all P values in the test of association were larger than 0.05. Nevertheless, pooling results in the "UK" subgroup of rs1801131, comprising five studies (1257 cases/1407 controls), indicated an elevated risk in colorectal polyp cases in comparison with controls, under the genetic models of CC vs. AA (P = 0.032, RR = 1.27, 95% CIs = 1.02, 1.57) and CC vs. AA+AC (P = 0.036, RR = 1.27, 95% CIs = 1.02, 1.60). CONCLUSION: The C/C genotype of MTHFR rs1801131 is more likely to be a genetic risk factor for colorectal polyps in the UK region, although this finding should be verified with a larger sample size.


Assuntos
Pólipos do Colo/genética , Predisposição Genética para Doença/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética/métodos , Estudos de Associação Genética/estatística & dados numéricos , Genótipo , Humanos , Fatores de Risco
7.
BMC Med Genet ; 20(1): 100, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170928

RESUMO

BACKGROUND: Cervical cancer has high prevalence and mortality rates in worldwide female population. Persistent infection by high-risk Human Papillomavirus (hr-HPV) is the main cause of this cancer. However, many environmental, genetical, and epigenetical cofactors can modulate viral infection and cervical carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been associated with many pathologies, including cancer. Nevertheless, studies with cervical cancer presented controversial results, and varied according to ethnicity. Thus, the aim of this study was to determine association between MTHFR C677T polymorphism, Human Papillomavirus (HPV) infection and cervical cancer. METHODS: A case-control study was performed with 150 histological cervical samples. Case group were divided in Cervical Intraepithelial Neoplasia (CIN) grade I (n = 30), CIN II (n = 30), CIN III (n = 30), and Squamous Cervical Carcinoma (SCC) (n = 30). Control group was composed by 30 samples without lesion, presenting cervicitis. HPV detection was performed by conventional Polymerase Chain Reaction (PCR) with SPF primers set, and by real-time PCR specific for HPV 16 and hr-HPV. MTHFR C677T polymorphism was analyzed by PCR followed by Restriction Fragment Length Polymorphism (RFLP). RESULTS: Frequency of MTHFR CC genotype was 72.7% (n = 109), CT 23.3% (n = 35) and TT 4.0% (n = 6). Polymorphic T allele frequency was 15.7%. No statistically significant association was observed between MTHFR C677T polymorphism and presence of pre-neoplastic or neoplastic cervical lesions. Similar frequencies of T allele was observed in control (23.3%) and cases (13.3%) groups (p = 0.174). In addition, there was no statistically significant association between MTHFR C677T polymorphism and viral infection, even considering hr-HPV or HPV 16 positivity. CONCLUSION: MTHFR C677T polymorphism was not associated with cervical cancer and HPV infection.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Infecções por Papillomavirus/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
8.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(3. Vyp. 2): 18-23, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184621

RESUMO

AIM: To study genetic characteristics of the population of the Moscow region and analyze the association of rs1801133 and rs1801131 of MTHFR with the risk of ischemic stroke (IS). MATERIAL AND METHODS: A sample of 170 and 115 patients with atherothrombotic and cardioembolic subtypes of IS and 360 residents of the Moscow region without IS were examined. MTHFR alleles were determined by a multiplex real-time polymerase chain reaction. RESULTS AND CONCLUSION: No association between the frequencies of MTHFR alleles and the risk of ischemic stroke was found. The comparison of allele frequencies with those in Caucasian populations published in the dbSNP (NCBI) and 1000 Genomes Project databases revealed significant differences for rs1801133 from the EUR 1000 Genomes Project. The allele frequency data for MTHFR could increase the accuracy and reliability of the individual risk calculation for multifactorial diseases in the Russian population.


Assuntos
Isquemia Encefálica , Predisposição Genética para Doença , Acidente Vascular Cerebral , Isquemia Encefálica/genética , Frequência do Gene , Genoma Humano , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Moscou , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Federação Russa , Acidente Vascular Cerebral/genética
9.
Croat Med J ; 60(3): 212-220, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31187948

RESUMO

AIM: To investigate the prevalence of common genetic variants that can serve as markers of thrombophilia and warfarin pharmacogenetics in Bosnia and Herzegovina. METHODS: The study was performed between August and October 2017 on 130 healthy unrelated adult volunteers from Bosnian-Herzegovinian population sample. The prevalence of the following genetic variants was determined: F5 c.1601G>A (factor V Leiden), F2 c.*97G>A (factor II or prothrombin mutation), F13A1 (factor XIII) c.103G>T, MTHFR (methylenetetrahydrofolate reductase) c.665C>T and c.1286A>C, as well as PAI-1 (plasminogen activator inhibitor 1) c.-816A>G and c.-844G>A as markers of thrombophilia risk, and *2 and *3 alleles of CYP2C9 (cytochrome P450 2C9) and five variants of VKORC1 (vitamin K epoxide reductase complex subunit 1) as markers of warfarin pharmacogenetics. DNA was isolated from buccal swabs using salting out method, while genotyping was performed using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. RESULTS: Minor allele frequencies for two main thrombophilia risk factors, F5 c.1601G>A and F2 c.*97G>A were 0.023 and 0.008, respectively. Combined data for the markers of warfarin pharmacogenetics imply that 57.4% study participants can be expected to metabolize warfarin at an extensive, 40.3% at intermediate, and 2.3% at a poor rate. CONCLUSION: This study reports the first extensive population genetic data for thrombophilia and warfarin pharmacogenetic markers in Bosnia and Herzegovina. Allele frequencies of genetic variants are within the general average for European populations, and their presence implies the necessity of introduction of personalized medicine in warfarin-mediated antithrombotic therapy.


Assuntos
Anticoagulantes/metabolismo , Fatores de Coagulação Sanguínea/genética , Trombofilia/genética , Varfarina/metabolismo , Adolescente , Adulto , Alelos , Biomarcadores , Bósnia e Herzegóvina , Citocromo P-450 CYP2C9/genética , Fator V/genética , Fator XIII/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Gravidez , Protrombina/genética , Vitamina K Epóxido Redutases/genética , Adulto Jovem
10.
Medicine (Baltimore) ; 98(24): e16037, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192962

RESUMO

BACKGROUND: The association between Methylenetetrahydrofolate Reductase (MTHFR) polymorphisms and lung cancer risk in Chinese people has been widely explored; however, the results remain controversial. Thus, we conducted a meta-analysis to investigate the association between MTHFR gene polymorphisms and susceptibility to lung cancer in Chinese people. OBJECTIVE: We performed an updated meta-analysis to investigate the association between MTHFR gene polymorphisms and susceptibility to lung cancer in Chinese people. METHODS: PubMed, EMBASE, WANFANG database, and CNKI were searched to collect eligible articles. The associations of MTHFR gene polymorphism with lung cancer risk were evaluated by calculating the pooled odds ratios (ORs) and the 95% confidence interval (CI). The dominant, recessive, heterozygous, homozygous, and allelic genetic models were used to calculate the combined ORs. RESULTS: A total of 16 eligible studies were identified in the present meta-analysis. Evidence from the pooled results indicated a significant association between the MTHFR C677T polymorphism and lung cancer susceptibility in Chinese people under the dominant, recessive, homozygous and allelic genetic models (T vs C: OR = 1.252, 95% CI, 1.090-1.437; TT vs CC: OR = 1.741, 95% CI, 1.252-2.420. (TT + CT) vs CC: OR = 1.227, 95% CI, 1.030-1.426. TT vs (CT + CC): OR = 1.606, 95% CI, 1.207-2.137). CONCLUSION: The present updated meta-analysis demonstrated that the MTHFR C677T polymorphism was significantly associated with susceptibility to lung cancer in Chinese people. Additional case-control studies with large sample sizes are needed to validate our findings.


Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , China , Humanos , Neoplasias Pulmonares/epidemiologia
11.
Ter Arkh ; 91(1): 71-77, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090375

RESUMO

AIM: To evaluate the association of a complex of cardiovascular risk factors and genetic markers with the development of high albuminuria among patients with arterial hypertension in the population of Mountain Shoriya, taking into account ethnicity. MATERIALS AND METHODS: A clinical epidemiological study of a compactly residing population in remote areas of Mountain Shoria was carried out. 1409 people were examined [901 people - representatives of the indigenous nationality (Shorians), 508 people - representatives of non-indigenous nationality (90% of them are Caucasians)]. Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and instrumental investigation. To study the state of the kidneys, the concentration (the presence of elevated levels) of albumin (albuminuria) in the morning portion of urine by an immunoturbidimetric method was analyzed. Polymorphisms of genes ACE (I/D, rs4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using PCR. RESULTS: In the group of shors with arterial hypertension, high albuminuria was associated with polymorphisms of the ACE genes (OR=2.05), ADRA2B (OR=6.00), elevated triglyceride level (OR=2.86), decreased index of cholesterol of high density lipoproteins (OR=5.57) and increased index of low density lipoproteins (OR=2.49); in the new population - with polymorphisms of the AGTR1 genes (OR=8.66), ADRA2B (OR=6.53), MTHFR (OR=7.16), obesity (OR=2.72), and abdominal obesity (OR=3.14). CONCLUSION: The primary predictors determining the development of high albuminuria among patients with arterial hypertension in both ethnic groups were genetic ones. In addition to them, non-genetic risk factors also contributed to the development of this organ damage to the kidneys: age and lipid metabolism disorders in representatives of indigenous nationality; age and abdominal obesity in the examined patients non-indigenous nationality.


Assuntos
Albuminas/metabolismo , Albuminúria/etnologia , Doenças Cardiovasculares/genética , Grupos Étnicos/genética , Hipertensão/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genética , Receptores Adrenérgicos alfa 2/genética , Albuminúria/genética , Doenças Cardiovasculares/etnologia , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Hipertensão/etnologia , Lipoproteínas HDL/metabolismo , Obesidade Abdominal/etnologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Fatores de Risco , Federação Russa/epidemiologia , Triglicerídeos/metabolismo
12.
Gene ; 707: 212-215, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31102717

RESUMO

BACKGROUND: Alzheimer's disease is a progressive, irreversible neurodegenerative disorder characterized by loss of memory and cognitive skills. More than 90% of cases are sporadic and have later age of onset. Many studies have shown a genetic predisposition for late onset Alzheimer's disease (LOAD). The most studied genetic predisposition factor is apolipoprotein E gene besides other susceptibility genes involved in vascular pathologies, homocysteine metabolism, and neuronal growth and differentiation such as methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), APOB and brain derived neurotrophic factor (BDNF). METHODS: In this study Factor V Leiden (G1691A) and H1299R, prothrombin G20210A, Factor XIII V34L, B-fibrinogen -455G>A, PAI-1 5G/4G, HPA1 b/a, MTHFR C677T, MTHFR A1298C, APOE, ACE I/D, BDNF C270T and G196A polymorphisms were evaluated in 100 LOAD patients and 100 age matched healthy controls. RESULTS: APOE4 allele, MTHFR CCA1298C and BDNF TTC270T genotypes were significantly higher in LOAD patients compared to the control group (p < 0.001, p = 0.04, p = 0.03, respectively). There were no significant associations between other genotypes and allele frequencies. Mini-Mental State Examination (MMSE) scores and age at onset of the patients were also evaluated for each and combined genotypes. Age at onset was significantly lowered by about approximately 4 and 5 years in patients carrying BDNF TTC270T and MTHFR TTC677T genotypes, respectively. CONCLUSION: APOE, MTHFR A1298C and BDNF C270T polymorphisms may be associated with LOAD and BDNF and MTHFR alleles may play a role in the age at onset of the LOAD.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
13.
Folia Neuropathol ; 57(1): 36-40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038186

RESUMO

Recent studies have reported elevated plasma homocysteine and reduced folate and vitamin B levels in patients with multiple sclerosis (MS). In this study, we aimed to investigate the association between MS and the following four DNA polymorphisms: MTR A[2756]G, MTHFR C[677]T, MTHFR A[1298]C and MTRR A[66]G. The DNA polymorphisms were genotyped in 80 patients with confirmed MS and 80 healthy control age- and gender-matched subjects using PCR-RFLP approach. Our results show that the frequency of the T/T genotype homozygotes for the MTHFR C[677]T polymorphism was significantly higher in patients than in controls (p = 0.04, OR: 3.16, 95% CI: 1.23-8.17). In turn, the A/A genotype of the MTHFR A[1298]C polymorphism was more frequent in controls than in patients (41.3% vs. 32.5%, p = 0.04). There were no differences in distribution of genotypes for the MTR A[66]G and MTR A[2756]C polymorphisms between patients with MS and controls (p > 0.05). Our findings suggested that the MTHFR C[677]T and MTHFR A[1298]C gene polymorphisms might be associated with MS as genetic factors influencing the risk of the disease.


Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/ultraestrutura , Ferredoxina-NADP Redutase/ultraestrutura , Predisposição Genética para Doença/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Esclerose Múltipla/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
Arch Endocrinol Metab ; 63(3): 280-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31066758

RESUMO

OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation that is associated with autoimmune pathology. We investigated the association between MTHFR genetic polymorphisms at g.677C>T and g.1298A>C and their haplotypes, and the risk of thyroid dysfunction among Jordanian females. SUBJECTS AND METHODS: A case-control study involving 98 hypothyroidism cases, 66 hyperthyroidism cases and 100 controls was conducted. Polymerase chain reaction/restriction fragment length polymorphism technique was performed to determine genotypes. Statistical analysis using SPSS software was performed. RESULTS: Genetic analysis showed a significant difference in genotype frequency of g.1298A>C between cases, and controls [hypothyroidism: AA (45.9%), AC (37.8%), CC (16.3%); hyperthyroidism: AA (9.1%), AC (69.7%), CC (21.2%); controls: AA (37.8%), AC (29.6%), CC (32.7%); CChypo vs. AAhypo: 2.55, 95% CI: (1.18-5.52); OR at least on Chypo: 1.79, 95% CI: (1.07-2.99)]; CChyper vs. AAhyper: 4.01, 95% CI: (1.79-9.01); OR at least on Chyper: 0.18, 95% CI: (0.07-0.48)]. There was no significant difference in genotype frequency of g.677C>T between cases and controls [hypothyroidism: CC (50.0%), CT (32.7%), TT (17.3%); hyperthyroidism: CC (77.3%), CT (15.2%), TT (7.6%); controls: CC (55.6%), CT (32.3%), TT (12.1%)]. There was a significant difference of MTHFR haplotypes among hypothyroidism cases and controls. TA and CC had a lower hypothyroidism risk whereas; TC showed a higher risk. CONCLUSIONS: g.1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease. CC, TA, and TC haplotypes affect the risk of hypothyroidism. Larger samples should be included in the future to verify the role of MTHFR polymorphisms in thyroid diseases.


Assuntos
Hipertireoidismo/genética , Hipotireoidismo/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Fragmento de Restrição/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Alelos , Estudos de Casos e Controles , Metilação de DNA , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Jordânia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Adulto Jovem
15.
BMJ Case Rep ; 12(4)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015243

RESUMO

Pyoderma gangrenosum (PG)-like ulcerations are a rare clinical manifestation of methylenetetrahydrofolate reductase (MTHFR) mutation. We describe a patient considered to have PG who was treated with long-term high doses of systemic corticosteroids and multiple immunosuppressive agents for several years. In spite of this continuous aggressive therapy, the lesions did not improve but continued to get worse. She developed many significant and catastrophic side effects to them. When referred to our dermatology centre, on investigation, it was discovered that she has an MTHFR mutation. It seemed reasonable to presume that PG-like lesions were related to it. Treatment with a biologically active form of folate-[6S]-5-MTHF-with vitamins B6 and B12 was initiated. It was considered to be beneficial and capable of reducing hyperhomocysteinaemia and endothelial damage consequent from it. Since the institution of this treatment, the patient has begun to show very gradual but slow and incremental improvement.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pioderma Gangrenoso/patologia , Úlcera Cutânea/patologia , Tetra-Hidrofolatos/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Pessoa de Meia-Idade , Mutação , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/tratamento farmacológico , Doenças Raras , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/genética , Tetra-Hidrofolatos/administração & dosagem , Resultado do Tratamento , Vitamina B 12/administração & dosagem , Vitamina B 12/uso terapêutico , Vitamina B 6/administração & dosagem , Vitamina B 6/uso terapêutico , Complexo Vitamínico B/uso terapêutico
16.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999684

RESUMO

Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman's rho = 0.420, p = 0.012) and vitamin B12 (rho = -0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09-55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of GT.


Assuntos
Alcatrão/uso terapêutico , Ceratolíticos/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Psoríase/terapia , Terapia Ultravioleta/métodos , Adulto , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Testes para Micronúcleos , Micronutrientes/sangue , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/patologia , Vitamina B 12/sangue
17.
Ann Clin Lab Sci ; 49(2): 232-236, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31028069

RESUMO

BACKGROUND: Evidences about the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and metabolic syndrome are controversial. The present study aimed to investigate if MTHFR gene polymorphisms MTHFR C677T and MTHFR A1298C are related to metabolic syndrome (MS). METHODS: 318 patients were enrolled and single nucleotide polymorphisms for MTHFR C667T and A1298C were genotyped. BMI, fasting blood glucose level (FBG), total cholesterol (TC), low-density lipoprotein (LDL), High-density lipoprotein (HDL) and triglycerides (TG) were measured. RESULTS: In our study population, there were no significant differences for BMI, FBG, TC, LDL, TG or any component disease of MS between MTHFR C667T, MTHFR A1298C wild type and variants. MTHFR A1298C wild type had significant higher HDL level than MTHFR A1298C variants (50.9±1.6 VS. 47.1±1.0, P=0.036). Binary logistic regression analysis also showed that MTHFR A1298C variants were significantly associated with lower HDL level (OR=0.963, 95%CI 0.93-0.99, P=0.027). General linear model showed that there was no statistically significant interaction between MTHFR C667T and A1298C gene polymorphism on HDL level. So the reduction in HDL in MTHFR 1298 variants was not due to its linkage disequilibrium with the C677T polymorphism or an interaction between MTHFR 677 and MTHFR 1298 genotypes. CONCLUSION: Our study suggests that MTHFR C667T gene polymorphism is not related to any components of metabolic syndrome. MTHFR 1298 variants were significantly associated with lower HDL level compared to MTHFR 1298 wild type.


Assuntos
HDL-Colesterol/sangue , Estudos de Associação Genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino
18.
Gene ; 704: 68-73, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986448

RESUMO

AIM: The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism. METHODS: The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP. RESULTS HIGHER: Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts. CONCLUSION: The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.


Assuntos
Aborto Habitual/genética , Metilação de DNA , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pré-Eclâmpsia/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Homocistinúria/complicações , Homocistinúria/genética , Humanos , Índia , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Espasticidade Muscular/complicações , Espasticidade Muscular/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/diagnóstico , Gravidez , Segundo Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/genética , Transtornos Psicóticos/complicações , Transtornos Psicóticos/genética
19.
Fertil Steril ; 111(5): 982-990.e2, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30922641

RESUMO

OBJECTIVE: To evaluate the impact of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with clinical data analysis in controlled ovarian hyperstimulation (COH) of infertile women in the Intravenous Infusion Safety Evaluation Center of Hunan Province, People's Republic of China. DESIGN: Genetic Association Study. SETTING: Reproductive medicine clinical. PATIENT(S): This genetic association study included 722 infertile women who received the standard long treatment protocol with accessible and complete electronic medical records. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The clinical parameters were obtained from the Intravenous Infusion Safety Evaluation center. RESULT(S): Basal FSH levels in the TT group were significantly higher than those of the CC group. The FSH levels after down-regulation in the TT group were higher than those of CC/CT genotypes. The TT genotype patients received significantly higher total doses of GnRH agonist and FSH compared with CC/CT genotypes, whereas the total dose of hCG was higher in the CT genotypes compared with the CC/TT genotypes. Further association analysis between hormone levels and COH outcomes indicated significantly negative correlation of basal FSH levels with antral follicle count and number of oocytes as well as the down-regulation FSH levels with the number of metaphase II oocytes and oocytes. CONCLUSION(S): The MTHFR C677T polymorphism was associated with high doses of ovarian stimulation medications, as well as higher FSH levels. The negative correlation between FSH levels and the number of oocytes suggested that C677T polymorphism may play a role in the poor prognosis of COH oocytes. This needs to be studied in future prospective studies with longer follow-up.


Assuntos
Hormônio Foliculoestimulante/sangue , Estudos de Associação Genética/métodos , Infertilidade Feminina/sangue , Infertilidade Feminina/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Indução da Ovulação/métodos , Adulto , Biomarcadores/sangue , Bases de Dados Factuais , Feminino , Humanos , Infertilidade Feminina/terapia , Polimorfismo Genético/genética , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
20.
Indian Pediatr ; 56(2): 143-144, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30819996

RESUMO

INTRODUCTION: Glanzmann thrombasthenia is a rare congenital platelet dysfunction. CASE CHARACTERISTICS: A 2-day-old male neonate delivered at 35 weeks' gestation was referred with extensive bruising and jaundice. His elder sibling had Glanzmann thrombasthenia, and his mother had thrombophilic risk factors. Flow cytometric analysis revealed absent CD41/CD61. A molecular thrombophilia panel revealed the presence of heterozygous factor V Leiden G1691A and methylenetetrahydrofolate reductase C677T gene mutations. OUTCOME: General precautions to avoid injuries and spontaneous bleeding were advised. MESSAGE: Life-threatening bleeding may not be the first finding in cases of thrombasthenia accompanied by thrombophilic risk factors.


Assuntos
Trombastenia , Adulto , Fator V/genética , Feminino , Humanos , Recém-Nascido , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Gravidez , Trombastenia/diagnóstico , Trombastenia/genética
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