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1.
Anticancer Res ; 39(10): 5375-5380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570432

RESUMO

BACKGROUND/AIM: Matrix metalloproteinases-11 (MMP-11) overexpression has been reported in various types of cancer including lung cancer. We aimed to examine the contribution of MMP-11 genotypes to lung cancer risk. MATERIALS AND METHODS: In this case-control study, the MMP-11 rs738791, rs2267029, rs738792 and rs28382575 genotypes were determined among 358 lung cancer patients and 716 age- and gender-matched healthy control Taiwanese. RESULTS: The percentages of rs738791 CT and TT were 50.6% and 9.2% in the case group, slightly higher than 48.5% and 8.1% in the control group (p for trend=0.5638). The allelic analysis showed that the rs738791 T allele did not confer lung cancer risk compared with the C allele. Similarly, there was no association between rs2267029, rs738792 or rs28382575 and lung cancer risk. There was no joint effect of MMP-11 genotypes among ever smokers or non-smokers. CONCLUSION: The genotypes of MMP-11 play a minor role in determining lung cancer risk in Taiwan.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Metaloproteinase 11 da Matriz/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
2.
Medicine (Baltimore) ; 98(38): e17224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567981

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS. METHODS: Pubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS. RESULTS: A total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians. CONCLUSION: FOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies. LEVEL OF EVIDENCE: Level III diagnostic study.


Assuntos
Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Genes/genética , Humanos , Esclerose Múltipla/etiologia
3.
Anticancer Res ; 39(10): 5525-5530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570446

RESUMO

BACKGROUND/AIM: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes. MATERIALS AND METHODS: DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A. RESULTS: The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls. CONCLUSION: Increased expression of AGT may be associated with BCC.


Assuntos
Carcinoma Basocelular/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinogênio/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética
4.
Tumour Biol ; 41(8): 1010428319869096, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31405342

RESUMO

Variable association of transforming growth factor beta 1 (TGFß1) in breast cancer (BC) pathogenesis was documented, and the contribution of specific TGFB1 polymorphisms to the progression of BC and associated features remains poorly understood. We investigated the contribution of TGFB1 rs1800469, rs1800470, rs1800471, and rs1800472 variants and 4-locus TGFB1 haplotypes on BC susceptibility, and pathological presentation of BC subtypes. Study subjects comprised 430 female BC cases, and 498 cancer-free control women. BC-associated pathological parameters were also evaluated for correlation with TGFB1 variants. Results obtained showed that the minor allele frequency (MAF) of rs1800471 (+74G>C) was higher seen in BC cases than in control subjects, and was associated with increased risk of BC. Significant differences in rs1800471 and rs1800469 (-509C>T) genotype distribution were noted between BC cases and controls, which persisted after controlling for key covariates. TGFB1 rs1800472 was positively, while rs1800470 was negatively associated with triple negativity, while rs1800470 positively correlated with menarche, but negatively with tumor size and molecular type, and rs1800469 correlated positively with menstrual irregularity, distant metastasis, nodal status, and hormonotherapy. Heterogeneity in LD pattern was noted between the tested TGFB1 variants. Four-locus (rs1800472-rs1800471-rs1800470-rs1800469) Haploview analysis identified haplotype TGCT to be negatively associated, and haplotypes CGTT and CCCC to be positively associated with BC. This association of CGTT and CCCC, but not TGCT, with BC remained significant after controlling for key covariates. In conclusion, TGFB1 alleles and specific genotypes, and 4-locus TGFB1 haplotypes influence BC susceptibility, suggesting dual association imparted by specific SNP, consistent with dual role for TGFB1 in BC pathogenesis.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Polimorfismo de Nucleotídeo Único/genética , Fator de Crescimento Transformador beta1/genética , Alelos , Feminino , Frequência do Gene/genética , Humanos , Pessoa de Meia-Idade , Tunísia
5.
An Bras Dermatol ; 94(3): 287-292, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365656

RESUMO

BACKGROUND: Renal transplant recipients are submitted to immunosuppression to avoid graft rejection, which makes them susceptible to various conditions. Furthermore, these individuals present malignant tumors more frequently than the general population, including nonmelanoma skin cancer. The individual genetic basis that acts in the pathogenesis of cutaneous cancer may present a protection or susceptibility factor for disease development. One of these factors is the HLA complex. OBJECTIVE: To investigate HLA alleles association to the occurrence of nonmelanoma skin cancer in renal transplant recipients from São Paulo State. METHODS: A total of 213 patients (93 renal transplant recipients with nonmelanoma skin cancer and 120 renal transplant recipients without nonmelanoma skin cancer) were evaluated by retrospective and cross-sectional study. Epidemiological, clinical and HLA typing data were found in databases. HLA class I (A, B) and class II (DR) alleles were compared to establish their association with nonmelanoma skin cancer. RESULTS: Comparing renal transplant recipients with and without nonmelanoma skin cancer, the HLA-B*13 allele was associated with higher risk of developing nonmelanoma skin cancer while B*45 and B*50 alleles were associated with protection. STUDY LIMITATIONS: The HLA A, B and DR alleles identification for the kidney transplantation routine is done by low and medium resolution techniques that do not allow discrimination of specific alleles. CONCLUSION: The involvement of HLA alleles in nonmelanoma skin cancer in renal transplant recipients was confirmed in this study. Renal transplant recipients with HLA-B*13 showed higher risk for developing a skin cancer (OR= 7.29) and should be monitored for a long period of time after transplantation.


Assuntos
Antígenos HLA/genética , Transplante de Rim/efeitos adversos , Neoplasias Cutâneas/genética , Adulto , Idoso , Alelos , Brasil/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Predisposição Genética para Doença/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Transplantados
6.
Am J Orthod Dentofacial Orthop ; 156(1): 104-112.e3, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256822

RESUMO

INTRODUCTION: Mandibular prognathism (MP) is subject to major polygenic influence and segregates within families in autosomal dominance with variable expressivity and incomplete penetrance. We aimed to identify the inheritance pattern and genes and loci involved in the development of MP in Mediterranean families and to evaluate the dentoskeletal characteristics of affected individuals. METHODS: Fifty-one eastern Mediterranean families with individuals affected by MP were identified. Data and biospecimens were collected from 14 of the families, including clinical examination, lateral cephalography (on subjects with Class III malocclusion), and 5 mL blood drawn from consenting affected and nonaffected relatives. Next-generation sequencing (NGS) was performed on 8 families (7 Lebanese, 1 Lebanese/Syrian), including large numbers of affected individuals over many generations and severe conditions, with the use of whole-exome sequencing. RESULTS: Most pedigrees suggested autosomal-dominant inheritance with an equal number of affected male and female individuals. Affected individuals had macrognathic and prognathic mandibles with dentoalveolar compensation. Genetic screening did not correspond with previously reported MP-linked genes, but yielded 3 novel genes (C1orf167, NBPF8, NBPF9) on chromosome 1 potentially responsible for mandibular development and macrognathism. CONCLUSIONS: In this first genetic study with the use of NGS on the largest reported number of families with MP, novel genes (C1orf167, NBPF8, NBPF9) were associated with familial MP in the eastern Mediterranean population.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença/genética , Má Oclusão de Angle Classe III/genética , Prognatismo/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Cefalometria , Cromossomos Humanos Par 1/genética , Feminino , Genoma Humano , Humanos , Líbano , Masculino , Má Oclusão de Angle Classe III/sangue , Má Oclusão de Angle Classe III/diagnóstico por imagem , Má Oclusão de Angle Classe III/patologia , Pessoa de Meia-Idade , Linhagem , Prognatismo/sangue , Prognatismo/diagnóstico por imagem , Prognatismo/patologia , Análise de Sequência de DNA , Síria , Adulto Jovem
8.
Medicine (Baltimore) ; 98(30): e16556, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348278

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.


Assuntos
Poluentes Atmosféricos/toxicidade , Epóxido Hidrolases/genética , Cardiopatias Congênitas/genética , Exposição Materna/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Estudos de Casos e Controles , China , Feminino , Feto/metabolismo , Predisposição Genética para Doença/embriologia , Predisposição Genética para Doença/genética , Cardiopatias Congênitas/embriologia , Humanos , Modelos Logísticos , Mães , Razão de Chances , Polimorfismo de Nucleotídeo Único , Gravidez
9.
BMC Med Genet ; 20(1): 97, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164103

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. The objective of this study was to investigate the association of ANGPTL4 gene variants (E40K) with fasting serum triglyceride levels and with cardiovascular risk factors, that included the presence of MetS in 817 subjects recruited from the Mashhad stroke and heart Atherosclerosis Disorders (MASHAD) cohort Study. METHOD: ANGPTL4 genotypes were determined using a TaqMan genotyping based real time PCR method. The association of the genetic variant with the risk of metabolic syndrome and its relationship with lipid profile were determined. RESULT: The frequency of GG, GA and AA genotypes were 96.9, 2.7 and 0.4% in individuals with MetS, and 78.8, 20.8, 0.4%, in those without MetS. The GA genotype of the rs116843064 polymorphism was associated with a lower risk for MetS (e.g., OR in Codominant genetic model: 0.14, 95% CI: (0.06-0.33), p < 0.0001). Subject with an A allele had a higher risk for MetS (OR: 6.72, 95% CI: (3.05-14.82), p < 0.0001). There was a significant difference in fasted lipid profiles across the genotypes for ANGPTL4. Carriers of the AG genotype had higher levels of serum HDL-cholesterol (HDL-C) and lower TG, compared to the GG homozygotes genotype. CONCLUSION: The G allele at the rs116843064 polymorphic locus of the ANGPTL4 gene was associated with a lower prevalence of MetS.


Assuntos
Proteína 4 Semelhante a Angiopoietina/genética , Aterosclerose/genética , Predisposição Genética para Doença/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Aterosclerose/sangue , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue
10.
BMC Med Genet ; 20(1): 99, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170924

RESUMO

BACKGROUND: Metabolic syndrome (MetS), defined as a cluster of metabolic risk factors including dyslipidemia, insulin-resistance, and elevated blood pressure, has been known as partly heritable. MetS effects the lives of many people worldwide, yet females have been reported to be more vulnerable to this cluster of risks. METHODS: To elucidate genetic variants underlying MetS specifically in females, we performed a genome-wide association study (GWAS) for MetS as well as its component traits in a total of 9932 Korean female subjects (including 2276 MetS cases and 1692 controls). To facilitate the prediction of MetS in females, we calculated a genetic risk score (GRS) combining 14 SNPs detected in our GWA analyses specific for MetS. RESULTS: GWA analyses identified 14 moderate signals (Pmeta < 5X10- 5) specific to females for MetS. In addition, two genome-wide significant female-specific associations (Pmeta < 5X10- 8) were detected for rs455489 in DSCAM for fasting plasma glucose (FPG) and for rs7115583 in SIK3 for high-density lipoprotein cholesterol (HDLC). Logistic regression analyses (adjusted for area and age) between the GRS and MetS in females indicated that the GRS was associated with increased prevalence of MetS in females (P = 5.28 × 10- 14), but not in males (P = 3.27 × 10- 1). Furthermore, in the MetS prediction models using GRS, the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was higher in females (AUC = 0.85) than in males (AUC = 0.57). CONCLUSION: This study highlights new female-specific genetic variants associated with MetS and its component traits and suggests that the GRS of MetS variants is a likely useful predictor of MetS in females.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Fenótipo , República da Coreia , Fatores de Risco , Fatores Sexuais
11.
BMC Med Genet ; 20(1): 102, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174489

RESUMO

BACKGROUND: Multiple factors are implicated in the etiology and pathogenesis of Abdominal Aortic Aneurysms (AAA). Available literature of genetic studies has previously suggested the possible roles of autoimmunity, genetic predisposition and ethnic susceptibility. Due to the association with autoimmune diseases and proven application in population genetics, we aimed to investigate alleles of the Class II Human Leukocyte Antigens (HLA-DRB1) in the Mexican Mestizo population with aortic aneurysms and determine possible associations with susceptibility. METHODS: We performed a case Control Study; the HLA molecular typing was completed for DRB1 loci by LabType Sequence-Specific Oligonucleotide (SSO) SSO-OneLambda kit (Applied Biosystems; Thermo Fisher Scientific. Inc.) in the studied individuals. Allele frequencies (af) were determined, associations were assessed by chi square or fisher exact tests at significance level (< 0.05), and Odds Ratios (OR) were calculated using the STATA software version 14. RESULTS: The genetic polymorphism of HLA-DRB1 of fifty one patients (70% males with a mean age of 71 years) with atherosclerotic or also known as degenerative AAA were compared with 99 unrelated patients (60% males, mean age 65 years) without the disease [Control group (CG)] from the same ethnic group. We examined a total of 102 Class II HLA-DRB1 alleles of AAA patients and 198 from CG. When comparing af, we observed the HLA-DRB1*01 af of 0.139 in the AAA compared to 0.05 in the CG [p = 0.015, OR 3, 95% confidence interval (CI) 1.29-7.08], the HLA-DRB1*16 af were 0.109 in the AAA and 0.025 in CG (p = 0.006, OR 4.7, 95% CI 1.59-13.98). CONCLUSIONS: Our study confirmed increased frequencies of the alleles HLA-DRB1*01 and HLA-DRB1*16 and their association to the development of AAA in Mexican Mestizo patients. The utility of genetic testing may assist in identifying individuals at genetic risk for the development of this disease in different ethnic groups, who might benefit from earlier ultrasound screening and closer imaging surveillance.


Assuntos
Aneurisma da Aorta Abdominal/genética , Grupos Étnicos/genética , Predisposição Genética para Doença/genética , Cadeias HLA-DRB1/genética , Polimorfismo Genético , Idoso , Alelos , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/etnologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Humanos , Masculino , México , Pessoa de Meia-Idade
12.
BMC Med Genet ; 20(1): 104, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185929

RESUMO

BACKGROUND: A multidirectional relationship has been demonstrated between myocardial infarction (MI) and depression. However, the causal genetic factors and molecular mechanisms underlying this interaction remain unclear. The main purpose of this study was to identify potential candidate genes for the interaction between the two diseases. METHODS: Using a bioinformatics approach and existing gene expression data in the biomedical discovery support system (BITOLA), we defined the starting concept X as "Myocardial Infarction" and end concept Z as "Major Depressive Disorder" or "Depressive disorder". All intermediate concepts relevant to the "Gene or Gene Product" for MI and depression were searched. Gene expression data and tissue-specific expression of potential candidate genes were evaluated using the Human eFP (electronic Fluorescent Pictograph) Browser, and intermediate concepts were filtered by manual inspection. RESULTS: Our analysis identified 128 genes common to both the "MI" and "depression" text mining concepts. Twenty-three of the 128 genes were selected as intermediates for this study, 9 of which passed the manual filtering step. Among the 9 genes, LCAT, CD4, SERPINA1, IL6, and PPBP failed to pass the follow-up filter in the Human eFP Browser, due to their low levels in the heart tissue. Finally, four genes (GNB3, CNR1, MTHFR, and NCAM1) remained. CONCLUSIONS: GNB3, CNR1, MTHFR, and NCAM1 are putative new candidate genes that may influence the interactions between MI and depression, and may represent potential targets for therapeutic intervention.


Assuntos
Biologia Computacional/métodos , Mineração de Dados/métodos , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Infarto do Miocárdio/genética , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Reprodutibilidade dos Testes
13.
BMC Med Genet ; 20(1): 105, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185933

RESUMO

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is an autosomal dominant genetic disorder that is characterized by specific abnormalities of the anterior segment of the eye. Heterozygous mutations in two developmental transcription factor genes PITX2 and FOXC1 have been identified within ARS patients, accounting for 40 to 70% of cases. Our purpose is to describe clinical and genetic findings in a Chinese family with ARS. METHODS: An ARS family with three affected members was recruited. The patients underwent a series of complete ophthalmologic examinations, general physical examination and dental radiography. DNA samples of proband II-1 were used for targeted exome sequencing of the FOXC1 and PITX2 genes. Sanger sequencing was used to validate the variation in PITX2. Quantitative real-time PCR was carried out to detect the expression of PITX2 in patients and normal controls. RESULTS: All affected members showed iris atrophy, corectopia, shallow anterior chamber, complete or partial angle closure, and advanced glaucoma. In addition, they revealed systemic anomalies, including microdontia, hypodontia, and redundant periumbilical skin. A novel heterozygous frameshift variation, c.515delA, in PITX2 was found in the proband, which might lead to a truncated PITX2 protein (p.Gln172ArgfsX36). Sanger sequencing validated that the variation completely cosegregated with the ARS phenotype among this family, but was absent in 100 unrelated controls. Quantitative real-time PCR analysis revealed that the mRNA expression of PITX2 was significantly decreased in patients compared with that in unrelated normal controls. CONCLUSIONS: PITX2 c.515delA (p.Gln172ArgfsX36) was the genetic etiology of our pedigree. The mutation led to decreased PITX2 gene expression and a truncated mRNA transcript.


Assuntos
Segmento Anterior do Olho/anormalidades , Anormalidades do Olho/genética , Oftalmopatias Hereditárias/genética , Mutação da Fase de Leitura , Predisposição Genética para Doença/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Sequenciamento Completo do Exoma/métodos , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , China , Anormalidades do Olho/etnologia , Oftalmopatias Hereditárias/etnologia , Saúde da Família , Feminino , Predisposição Genética para Doença/etnologia , Humanos , Masculino , Linhagem , Adulto Jovem
14.
BMC Med Genet ; 20(1): 107, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31195986

RESUMO

BACKGROUND: Type 2 diabetes mellitus is believed to be a polygenic disorder that develops as a result of a complex interaction between multiple genes and environmental factors. KCNJ11 gene encodes a Kir6.2 protein which forms the inner section of the potassium channels in pancreatic beta cells. Several studies found that KCNJ11 polymorphism increases T2DM risk. Our study aimed to investigate the association between rs5219 polymorphism of the KCNJ11 gene and T2DM in Syrian patients. METHODS: This case-control study involved 75 T2DM patients and 63 healthy controls. The KCNJ11 rs5219 polymorphism was genotyped by Restriction Fragment Length Polymorphism (RFLP). RESULTS: The frequency of the risk allele K was similar between the two groups (38.7% vs. 38.1%, P = 0.132). The frequency of the KK genotype was higher among the patients' group (16% vs. 4.8%), and the frequency of the EK genotype was higher among the control group (45.3% vs. 66.6%); however, the differences were statistically insignificant. The KK genotype was significantly associated with T2DM in the recessive model with an OR of 3.81 (95% CI 1.024-14.17, P = 0.035). CONCLUSIONS: This study showed that rs5219 polymorphism of the KCNJ11 gene is an important risk factor for type 2 diabetes mellitus in a sample of the Syrian population.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genética Populacional , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Síria
15.
BMC Med Genet ; 20(1): 106, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196117

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a human autosomal-recessive hypopigmentation disorder with hypopigmentation in the skin, hair, and eyes. OCA1 and OCA2 are caused by mutations of the TYR and OCA2 genes, respectively, which are responsible for most oculocutaneous albinism. However, the incidence of oculocutaneous albinism patients in Guangxi remains unclear. METHODS: To evaluate the molecular basis of oculocutaneous albinism in thirty-six patients in Guangxi, China. Peripheral venous blood samples were collected from these unrelated patients. The TYR and OCA2 genes of all individuals were analyzed by direct DNA sequencing and the sequences compared with are reference database and bioinformatics analysis. RESULTS: Among the 36 OCA patients, 8(22.2%) were found mutations on TYR gene, 28 (77.8%) on OCA2. And we identified Twenty-seven different TYR and OCA2 mutations in these patients, including one novel TYR framshift mutation c.561_562insTTATTATGTGTCAAATTATCCCCCA, three novel OCA2 mutations: one nonsense mutation c.2195C > G(p.S732X), one deletation mutation(c.1139-1141delTGG), one missense mutations c.2495A > C(p.H832P). The population screening and the bioinformatic analysis to determined the effects of the mutations, which revealed these four novel mutations were pathogenic. CONCLUSIONS: This study expands the mutation spectrum of oculocutaneous albinism. Four novel mutational alleles c.1139-1141delTGG, c.1832 T > C and c.2195C > G and of the OCA2 gene and c.561_562insTTATTATGTGTCAAATTATCCCCCA of TYR were associated with OCA. The genotype-phenotype correlations suggest that molecular diagnosis is more accurate and important in OCA.


Assuntos
Albinismo Oculocutâneo/genética , Análise Mutacional de DNA/métodos , Predisposição Genética para Doença/genética , Mutação , Adolescente , Adulto , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Sequência de Bases , Criança , Pré-Escolar , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/etnologia , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas de Membrana Transportadoras/genética , Monofenol Mono-Oxigenase/genética
16.
Medicine (Baltimore) ; 98(23): e15828, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169684

RESUMO

BACKGROUND: The K channel, subfamily J, member-11 (KCNJ11) E23K and ß1 subunit of large-conductance Ca-activated K channel (KCNMB1) E65K polymorphisms were shown to be associated with the risk of essential hypertension (EH). However, the results were inconclusive with relatively small sample size. Thus, we carried out a meta-analysis to investigate the genetic association between KCNJ11 E23K and KCNMB1 E65K polymorphisms and essential hypertension risk. METHODS: Relative studies were collected using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure and Embase databases. Pooled odds ratios with 95% confidence intervals were used to assess the strength of associations. RESULTS: The dominant models of KCNJ11 E23K (P = .006, OR [95%CI] = 0.45 [0.25, 0.79]) and KCNMB1 E65K (P = .04, OR [95%CI] = 0.91 [0.83, 1.00]) were significantly associated with essential hypertension risk. No significant association was detected between the allelic and recessive models of KCNJ11 E23K and KCNMB1 E65K and the susceptibility of EH. Subgroup analysis stratified by ethnicity showed that the dominant model of KCNMB1 E65K was associated with EH risk in Asian population (P = .003, OR [95%CI] = 0.83 [0.74, 0.94]), but not in Caucasian (P = .74, OR [95%CI] = 1.02 [0.89, 1.18]). CONCLUSIONS: The dominant model of KCNJ11 E23K and KCNMB1 E65K might be susceptible factors for essential hypertension. To confirm this result, large-scale case-control studies with more subjects are necessary.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hipertensão Essencial/genética , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade
17.
Medicine (Baltimore) ; 98(23): e15921, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169709

RESUMO

The study was performed to investigate the genetic associations of IGF-1 polymorphisms rs35767, rs5742714, and rs972936 with susceptibility to osteonecrosis of the femoral head (ONFH) among Chinese Han population.Totally, 101 ONFH patients and 128 healthy controls were enrolled. Hardy-Weinberg equilibrium (HWE) was detected with chi-square test in control group. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the relationship between IGF-1 polymorphisms and ONFH risk. Besides, hyplotype analysis was performed to examine linkage disequilibrium between the studied polymorphisms.Genotype AA and allele A of polymorphism rs35767 were more frequent in control group, and offered protection for ONFH onset (AA: OR = 0.382, 95% CI = 0.158-0.923; A: OR = 0.650, 95% CI = 0.442-0.956). Furthermore, the negative relationship was also observed between ONFH risk and polymorphism rs5742714 under the comparisons CG vs CC, and G vs C (OR = 0.395, 95%CI = 0.199-0.787; OR = 0.346, 95%CI = 0.191-0.627). While the polymorphism rs972936 significantly enhanced the disease risk (CT vs CC: OR = 2.434, 95% CI = 1.184-5.003; TT vs CC: OR = 2.497, 95% CI = 1.040-5.990). Furthermore, haplotype analysis demonstrated that C-T (rs5742714-rs972936) could increase ONFH risk (OR = 2.177, 95% CI = 1.444-3.283), while G-T might be a protective factor for ONFH (OR = 0.472, 95% CI = 0.254-0.878).IGF-1 polymorphisms rs35767, rs5742714, and rs972936 show significant association with ONFH risk.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Necrose da Cabeça do Fêmur/genética , Predisposição Genética para Doença/genética , Fator de Crescimento Insulin-Like I/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Alelos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Grupos Étnicos/genética , Feminino , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Razão de Chances
18.
Medicine (Baltimore) ; 98(23): e15953, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169720

RESUMO

BACKGROUND: Studies showed the controversial results about the effect of common genetic polymorphisms on the atrial fibrillation (AF) recurrence. We performed the systematic review and meta-analysis to qualify the association between common genetic polymorphisms and AF recurrence. METHODS: Articles were systematically retrieved PubMed, Web of Science, EMBASE, Wanfang, and CNKI database and 9 studies including 3204 patients were enrolled in our meta-analysis. RESULTS: Results showed that the associations were significant under rs2200733 3 genetic models (TT vs CC: odds ratio [OR] [confidence interval [CI]] = 1.336 [1.061-1.683], P = .014; CT vs CC: OR [CI] = 0.759 [0.614-0.937], P = .01; TT vs CT + CC: OR [CI] = 2.308 [1.440-3.700], P = .001). The association was significant under rs10033464 genetic model (TT vs GG: OR [CI] = 1.517 [1.165-1.976], P = .002). CONCLUSIONS: Rs13376333 on chromosome 1q21 (in KCNN3), rs7193343 and rs2106261 on chromosome 16q22 (in ZFHX3) were not associated with AF recurrence in our meta-analysis. In total, our meta-analysis found that rs2200733 and rs10033464 on chromosome 4q25 (near PITX2) were associated with the risk of AF recurrence.


Assuntos
Fibrilação Atrial/genética , Cromossomos Humanos/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Recidiva , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Fatores de Transcrição/genética
19.
Medicine (Baltimore) ; 98(23): e15955, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169721

RESUMO

Many studies have investigated the association between the 3'UTR polymorphism in natural resistance-associated macrophage protein 1 (NRAMP1) and the risk of pulmonary tuberculosis (PTB), Revealing inconclusive results. This study aimed to investigate the correlation between the NRAMP1 3'UTR polymorphism and the risk of PTB.This meta-analysis included 29 case-control studies to better and comprehensively assess this correlation. Pooled odds ratios (ORs) and 95% confidence interval (95% CIs) were calculated to assess the strength of the association.These 29 case-control studies included 4672 cases and 6177 controls. The NRAMP1 3'UTR polymorphism displayed a significant positive correlation with the risk of PTB in 3 models (for del/del vs ins/ins: OR = 1.22, 95% CI = 1.01-1.47; for Ins/del vs ins/ins: OR = 1.19, 95% CI 1.08-1.30; for Ins/del + del/del vs ins/ins: OR = 1.25, 95% CI = 1.08-1.45). A stratified analysis by ethnicity revealed that the NRAMP1 3'UTR polymorphism was associated with an increased risk of PTB in the Asian population, but not in Caucasian, African, and South American populations.The present results indicate that the NRAMP1 3'UTR polymorphism may be considered a risk factor for PTB in the Asian population.


Assuntos
Regiões 3' não Traduzidas/genética , Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Tuberculose Pulmonar/genética , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Razão de Chances , Fatores de Risco
20.
Yonsei Med J ; 60(7): 651-658, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31250579

RESUMO

PURPOSE: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17, RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. MATERIALS AND METHODS: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. RESULTS: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44-6.24 and 1.10-1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01-1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46-0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84-7.91). No associations were observed among common variants near EDNRA, SOX17, or RBBP8 and IA. CONCLUSION: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Aneurisma Intracraniano/genética , Polimorfismo de Nucleotídeo Único , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade
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