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1.
Gene ; 720: 144078, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473321

RESUMO

Short tandem repeats (STRs) are a widely utilized tool in forensic applications, the latter of which range from human identification and paternity testing to population analysis. The GlobalFiler STR loci, which includes 21 autosomal STRS, were analyzed in the Chechen subpopulation of Jordan. Whole blood samples were withdrawn from 159 Jordanian Chechen individuals, and genomic DNA was extracted from each sample. The GlobalFiler™ kit PCR Amplification Kit amplified and analyzed the STR loci on the 3130xl Genetic Analyzer using GeneMapper ID-X software. The combined match probability for the 21 autosomal STR loci was calculated to be 1.06 × 10-24, a number that is highly discriminatory and informative. The SE33 (0.983) and TPOX (0.806) loci exhibited the highest and lowest powers of discrimination, respectively. Conclusively, the current study indicates that the GlobalFiler loci have a high utility in the Jordanian Chechen population, possibly paving the way for the future establishment of a reference population database in Jordan.


Assuntos
DNA/análise , DNA/genética , Grupos Étnicos/genética , Genética Forense/estatística & dados numéricos , Genética Populacional , Repetições de Microssatélites , Polimorfismo Genético , Impressões Digitais de DNA , Feminino , Frequência do Gene , Loci Gênicos , Humanos , Masculino
2.
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
3.
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
4.
Hum Genet ; 138(7): 757-769, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168775

RESUMO

An ethnicity is characterized by genomic fragments, single nucleotide polymorphisms (SNPs), and structural variations specific to it. However, the widely used 'standard human reference genome' GRCh37/38 is based on Caucasians. Therefore, de novo-assembled reference genomes for specific ethnicities would have advantages for genetics and precision medicine applications, especially with the long-read sequencing techniques that facilitate genome assembly. In this study, we assessed the de novo-assembled Chinese Han reference genome HX1 vis-à-vis the standard GRCh38 for improving the quality of assembly and for ethnicity-specific applications. Surprisingly, all genomic sequencing datasets mapped better to GRCh38 than to HX1, even for the datasets of the Chinese Han population. This gap was mainly due to the massive structural misassembly of the HX1 reference genome rather than the SNPs between the ethnicities, and this misassembly could not be corrected by short-read whole-genome sequencing (WGS). For example, HX1 and the other de novo-assembled personal genomes failed to assemble the mitochondrial genome as a contig. We mapped 97.1% of dbSNP, 98.8% of ClinVar, and 97.2% of COSMIC variants to HX1. HX1-absent, non-synonymous ClinVar SNPs were involved in 140 genes and many important functions in various diseases, most of which were due to the assembly failure of essential exons. In contrast, the HX1-specific regions were scantly expressible, as shown in the cell lines and clinical samples of Chinese patients. Our results demonstrated that the de novo-assembled individual genome such as HX1 did not have advantages against the standard GRCh38 genome due to insufficient assembly quality, and that it is, therefore, not recommended for common use.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Genoma Humano , Genômica/normas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Padrões de Referência , Análise de Sequência de DNA/normas , Algoritmos , Mapeamento de Sequências Contíguas , Genética Populacional , Humanos , Polimorfismo de Nucleotídeo Único , Transcriptoma
5.
BMC Genomics ; 20(1): 459, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170919

RESUMO

BACKGROUND: The most widely used human genome reference assembly hg19 harbors minor alleles at 2.18 million positions as revealed by 1000 Genome Phase 3 dataset. Although this is less than 2% of the 89 million variants reported, it has been shown that the minor alleles can result in 30% false positives in individual genomes, thus misleading and burdening downstream interpretation. More alarming is the fact that, significant percentage of variants that are homozygous recessive for these minor alleles, with potential disease implications, are masked from reporting. RESULTS: We have demonstrated that the false positives (FP) and false negatives (FN) can be corrected for by simply replacing nucleotides at the minor allele positions in hg19 with corresponding major allele. Here, we have effectively replaced 2.18 million minor alleles Single Nucleotide Polymorphism (SNPs), Insertion and Deletions (INDELs), Multiple Nucleotide Polymorphism (MNPs) in hg19 with the corresponding major alleles to create an ethnically normalized reference genome called hg19KIndel. In doing so, hg19KIndel has both corrected for sequencing errors acknowledged to be present in hg19 and has improved read alignment near the minor alleles in hg19. CONCLUSION: We have created and made available a new version human reference genome called hg19KIndel. It has been shown that variant calling using hg19KIndel, significantly reduces false positives calls, which in-turn reduces the burden from downstream analysis and validation. It also improved false negative variants call, which means that the variants which were getting missed due to the presence of minor alleles in hg19, will now be called using hg19KIndel. Using hg19KIndel, one even gets a better mapping percentage when compared to currently available human reference genome. hg19KIndel reference genome and its auxiliary datasets are available at https://doi.org/10.5281/zenodo.2638113.


Assuntos
Grupos Étnicos/genética , Variação Genética , Genoma Humano , Alelos , Bases de Dados de Ácidos Nucleicos , Humanos , Mutação INDEL , Polimorfismo de Nucleotídeo Único , Padrões de Referência , Análise de Sequência de DNA
6.
Croat Med J ; 60(3): 191-200, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31187946

RESUMO

AIM: To determine allele frequencies and forensic statistics of 22 autosomal short tandem repeat loci in Chinese Mongolian population. METHODS: Blood specimens were collected from 134 unrelated healthy Mongolian individuals, and 22 short tandem repeat loci were co-amplified and genotyped. Allele frequencies and forensic parameters were calculated, and population genetic differences were analyzed among Mongolian population and other eight Chinese populations: Northern Han, Guangdong Han, Chengdu Han, Xinjiang Hui, Xinjiang Uygur, Hainan Li, Qinghai Tibetan, and Hainan Han. RESULTS: All the loci were in the Hardy-Weinberg equilibrium, and after Bonferroni correction there was no linkage disequilibrium between them. The allele frequencies of these 22 loci were between 0.0037 and 0.3657. This panel had high discriminating power and genetic polymorphism in the Mongolian population, with combined power of discrimination of 0.999999999999999999999999998399 and combined probability of exclusion of 0.9999999999566925. Structure analysis showed no evidence that these nine Chinese populations had different component distribution. However, genetic distance analysis showed significant differences among them (P<0.05). CONCLUSION: The combined application of these 22 loci could be useful for forensic purposes in the Mongolian population. Mongolian population had smaller genetic distances from the populations in northern China (Northern Han, Xinjiang Uygur, and Xinjiang Hui) than from the populations in Hainan province (Hainan Han and Hainan Li populations).


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Repetições de Microssatélites , Polimorfismo Genético , China , Feminino , Genética Forense , Frequência do Gene , Loci Gênicos , Testes Genéticos , Genética Populacional , Genótipo , Humanos , Masculino
7.
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
8.
Genet Test Mol Biomarkers ; 23(6): 393-400, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31063404

RESUMO

Background: The protein AXIN2 is involved in the negative feedback regulation of the Wnt/ß-catenin signaling pathway; it functions by promoting ß-catenin degradation. AXIN2 mutations have been studied in various cancers. In this study, we genotyped three single nucleotide polymorphisms in the AXIN2 gene and investigated their association with the risk of breast cancer (BC) in the Chinese Han population. Methods: In a population of 415 BC patients and 528 controls the expression of AXIN2 was measured using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and compared with the overall survival (OS) of BC patients analyzed through Oncomine and Kaplan-Meier plotter databases. Bioinformatic analyses demonstrated that AXIN2 mRNA levels were downregulated in BC patients; this in turn correlated with a poorer survival rate for BC patients. Results: The polymorphisms rs11079571 and rs3923087, but not rs3923086, were associated with an increased risk of BC. The minor allele containing genotypes of polymorphism rs3923087 were positively associated with lymph node metastases. A haplotype analysis demonstrated that the ATA haplotype was correlated with an increased risk of BC. Conclusion: In conclusion, the downregulation of AXIN2 is related to poorer OS for BC patients. Its polymorphisms rs11079571 and rs3923087 confer susceptibility to BC. These findings should be confirmed with larger studies that include more diverse ethnic populations.


Assuntos
Proteína Axina/genética , Neoplasias da Mama/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Proteína Axina/fisiologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , China , Grupos Étnicos/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Haplótipos/genética , Humanos , Metástase Linfática/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Fatores de Risco , Taxa de Sobrevida , Via de Sinalização Wnt/genética
9.
Genet Test Mol Biomarkers ; 23(6): 380-386, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31063409

RESUMO

Background: Hallux valgus (HV) is a type of forefoot deformity affecting ∼23% of adults. Previous studies have shown that HV is highly heritable. Tumor necrosis factor (TNF) is an important proinflammatory cytokine involved in bone remodeling and plays essential roles in osteoarthritis and chronic inflammatory bone diseases, including HV. Methods: A total of 1,788 Chinese women comprising 637 HV subjects and 1,151 controls were recruited. Twelve single nucleotide polymorphisms (SNPs) located in TNF and its promoter regions were selected and genotyped. Genetic association analyses were performed to investigate potential susceptibility SNPs. Bioinformatic and expression quantitative trait loci (eQTL) analyses were conducted to examine the functional consequences of the SNPs identified as being significantly associated with HV. Results: SNP rs1800629, which is located at the 5' end of the promoter region of TNF, was identified as significantly associated with HV status in Chinese women (OR = 0.56, p = 2.12 × 10-6). Bioinformatic analyses using RegulomeDB indicated that this SNP has important functional significance, but subsequent eQTL analyses did not identify a significant association between rs1800629 and TNF gene expression. In addition, 26 genes with cis-eQTL for rs1800629 were identified. Conclusions: This study identified a susceptibility SNP for HV located within the promoter region of the TNF gene. Bioinformatic and eQTL analyses linked this SNP to 26 genes but not to TNF. Functional studies are needed to more fully characterize the effects of this SNP.


Assuntos
Hallux Valgus/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Grupos Étnicos/genética , Feminino , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Hallux Valgus/metabolismo , Haplótipos/genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Fatores de Risco , Fator de Necrose Tumoral alfa/fisiologia
10.
Genet Test Mol Biomarkers ; 23(6): 373-379, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066581

RESUMO

Objective: Hip osteoarthritis (HOA) is one of the most common types of osteoarthritis and affects nearly 10% of men and 18% of women who are >60 years of age worldwide. It has been demonstrated to be a genetic disease with a 50% heritability risk. Recently, the TLR-9 gene has been associated with knee OA in both Turkish and Chinese populations, but the relationship between the TLR-9 gene and HOA has not been evaluated. In this study, we aimed to evaluate the relationship between the common genetic variants in the TLR-9 gene and the predisposition of Han Chinese individuals to HOA. Methods: A total of 730 HOA patients and 1220 healthy controls were recruited in a hospital-based case-control study. Six common single nucleotide polymorphisms (SNPs) of the TLR-9 gene were selected for genotyping, and genetic association analyses were performed using both single-marker and haplotype-based methods. Results: The SNP rs187084 was found to be significantly associated with the risk of HOA after a Bonferroni correction (adjusted allelic p-values with age, gender, and body mass index [BMI] = 0.0008). The results indicated that the A allele of rs187084 is a risk allele for HOA and is likely to be a predisposing factor leading to an increased risk of HOA (adjusted odds ratio with age, gender, and BMI = 1.26, 95% confidence interval = 1.10-1.43). The results of the haplotype analyses confirmed a similar pattern to the SNP analyses. Conclusions: Our study provides strong evidence that variations in the TLR-9 gene are closely linked with genetic susceptibility to HOA in the Han Chinese population. This finding furthers the role of TLR-9 in the development and occurrence of OA in general.


Assuntos
Osteoartrite do Quadril/genética , Receptor Toll-Like 9/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Grupos Étnicos/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
11.
Genet Test Mol Biomarkers ; 23(6): 428-432, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081706

RESUMO

Background: Autosomal recessive congenital ichthyoses (ARCI) are a group of rare nonsyndromic genodermatoses characterized by generalized scaly appearance of the epidermis with markedly impaired cutaneous barriers owing to defects in keratinization related genes. In this study, we ascertained a consanguineous Pakistani family affected with ARCI. Aims: To investigate genetic defect underlying disease phenotype in the affected family. Methods: All available members of the family (affected and unaffected) were sampled. Whole exome sequencing (WES) was performed on DNA of the proband and the data were analyzed for probable pathogenic variants. Segregation of the identified variant was validated by Sanger sequencing. Results: Analysis of the WES data identified a novel nonsense mutation, c.762C>G, in the PNPLA1 (patatin-like phospholipase domain containing 1) gene. The protein product of of this gene is involved in lipid organization during cornified cell envelope formation. The variant is predicted to result in the generation of a premature truncation site at amino acid position 254 (p.Tyr254*). This would result in the loss of a large C-terminal portion of the protein suggesting it to be rendered nonfunctional. In silico protein structure modeling confirmed a detrimental effect of the variation on protein structure. Conclusions: The study supports the evidence for the prevalence of PNPLA1 mutations in distant ethnic groups. Despite the significant number of reported ARCI cases with PNPLA1 variants, a straightforward genotype-phenotype correlation cannot be established.


Assuntos
Ictiose Lamelar/genética , Lipase/genética , Adulto , Idoso , Códon sem Sentido/genética , Grupos Étnicos/genética , Família , Feminino , Genes Recessivos/genética , Humanos , Ictiose Lamelar/metabolismo , Lipase/fisiologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Paquistão , Linhagem , Fenótipo , Sequenciamento Completo do Exoma/métodos
12.
Klin Lab Diagn ; 64(4): 243-249, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31108039

RESUMO

Conducted high-resolution HLA-typing loci HLA-A, -B, -C, -DRB1 and -DQB1 by massively parallel sequencing of 150 potential donors of hematopoietic stem cells from the Republic of Kalmykia. In the studied population, four new alleles identified that not previously registered by the International Committee on the Nomenclature of Factors of the HLA-system of WHO. During the HLA-typing identified: 29 alleles at the HLA-A locus, 44 - at the HLA-B locus, 26 - at the HLA-C locus, 15 - at the DQB1 locus, 37 - at the HLA-DRB1 locus. The following alleles have a frequency of more than 10%: HLA-A*02:01 (11,7%), HLA-A*01:01 (11%), HLA-B*51:01 (10,3%), HLA-B*58:01 (10,3%), HLA-C*06:02 (17,7%), HLA-C*03:04 (10,3%), HLA-C*03:02 (10%), HLA-DQB1*03:01 (26,7%), HLA-DQB1*02:02 (10%), HLA-DRB1*07:01 (11,7%). The most common HLA-A-B-C-DQB1-DRB1 haplotype is A*02:05-B*50:01-C*06:02-DQB1*02:02-DRB1*07:01 (3,7%). Deviations from the Hardy - Weinberg equilibrium not identified.


Assuntos
Alelos , Grupos Étnicos/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Haplótipos , Frequência do Gene , Antígenos HLA-C , Células-Tronco Hematopoéticas , Humanos , Federação Russa
13.
Biomed Res Int ; 2019: 9537050, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093505

RESUMO

Background: Because of the similarity of intestinal tuberculosis and Crohn's disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn's disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn's disease, and 700 normal controls in this study. Methods: All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. Results: The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn's disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn's patients requiring glucocorticoids (p<0.05). Conclusions: The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn's disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn's disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Doença de Crohn/genética , Epóxido Hidrolases/genética , Grupos Étnicos/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Tuberculose Gastrointestinal/genética , Adulto , Doença de Crohn/enzimologia , Feminino , Frequência do Gene/genética , Humanos , Masculino , Modelos Genéticos , Tuberculose Gastrointestinal/enzimologia
14.
Medicine (Baltimore) ; 98(22): e15891, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145348

RESUMO

CYP2D6 genetic variations could result in alteration of CYP2D6 enzyme activity, leading to dissimilarity among individuals in regard of drug metabolism.This study aims to detect all genetic variants, allele, and genotype frequencies of CYP2D6 gene in 136 unrelated healthy Kinh Vietnamese volunteers. All single nucleotide variants (SNVs) and structural variations (SVs) of CYP2D6 gene were identified by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay.Totally, 30 SNVs and 9 SVs including a whole gene deletion, 8 hybrid structures, and tandem arrangements were identified. Of the 7 novel SNVs detected, the 3157G>T (R329L) substitution was predicted to be deleterious by PROVEAN; the 3851G>A (W358X) variant resulted in a truncated protein; and the 2988G>A variant located in the intron 6 was predicted to be capable of modifying splicing motif by Human Splicing Finder. We determined 29 different genotypes of CYP2D6 from 136 individuals. The most common alleles were the CYP2D6*10 (43.75%), *1 (18.75%), and tandem arrangement *36-*10 (12.13%).This study provides best information on CYP2D6 polymorphism comprising the newly discovered SNVs, structural variations, and their frequencies in Kinh Vietnamese. These new data would be valuable in view of precise dosing of CYP2D6 metabolized drugs and giving better treatment outcome.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Citocromo P-450 CYP2D6/genética , Grupos Étnicos/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Feminino , Frequência do Gene , Genótipo , Humanos , Íntrons/genética , Desequilíbrio de Ligação , Masculino , Vietnã
15.
Med Sci Monit ; 25: 3390-3396, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064975

RESUMO

BACKGROUND This study aimed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphisms with left ventricular hypertrophy (LVH) in Han and Uighur hypertension-OSAHS (obstructive sleep apnea hypopnea syndrome) patients in China. MATERIAL AND METHODS A total of 162 Han and 72 Uygur patients with hypertension-OSAHS were independently subdivided into an LVH group and a non-LVH (NLVH) group based on the left ventricular mass index. The insertion/deletion polymorphisms of ACE gene were determined by polymerase chain reaction. The association of ACE gene insertion/deletion polymorphisms with LVH was assessed by chi-squared test. Logistic regression analysis was performed to obtain the odds ratios and 95% confidence intervals for the risk of LVH after adjusting for confounding factors. RESULTS In Uighur patients, the distributions of D allele and DD genotype showed significant differences between the LVH group and the NLVH group. The difference of DD genotype remained significant after multivariate adjustment. In contrast, no significant differences were observed in the distributions of D allele and DD genotype between the LVH group and the NLVH group in Han patients. Moreover, moderate-severe OSAHS was an independent risk factor for LVH. CONCLUSIONS D allele and DD genotype of ACE gene are possible genetic markers for the risk of LVH in Uighur but not Han hypertension-OSAHS patients.


Assuntos
Hipertrofia Ventricular Esquerda/genética , Peptidil Dipeptidase A/genética , Apneia Obstrutiva do Sono/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , China , Grupos Étnicos/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Hipertensão/complicações , Hipertensão/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Mutação INDEL/genética , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Fatores de Risco , Apneia Obstrutiva do Sono/complicações
16.
Genet Test Mol Biomarkers ; 23(5): 316-324, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942616

RESUMO

Objective: Perindopril is an angiotensin-converting enzyme (ACE) inhibitor that is commonly used in the treatment of Chinese Han patients with acute myocardial infarction (AMI). However, there have been few studies on whether polymorphisms of the ACE gene affect the efficacy of perindopril or the prognosis of AMI patients. The purpose of this study was to analyze the relationship among the ACE rs121912703 (C>T), rs767880620 (C>A), and rs397514689 (C>T) gene polymorphisms and the prognosis of AMI patients and the clinical efficacy of perindopril in the treatment of AMI. Methods: The ACE genotypes at the rs121912703, rs767880620, and rs397514689 loci in 225 AMI patients treated with perindopril were determined by polymerase chain reaction/Sanger sequencing. Differences in cardiac structure, functional indicators, hemodynamic parameters, and related laboratory indicators were detected before and after treatment. Results: After administration of perindopril, improved ventricular remodeling in AMI patients with wild-type ACE was better than in patients with the ACE rs121912703, rs767880620, and rs397514689 minor variant alleles. The patients harboring wild-type ACE had lower systolic blood pressure and diastolic blood pressure than the patients harboring the minor variant alleles (p < 0.01). The contents of serum ACE and Ang II (angiotensin II) in AMI patients carrying the wild-type ACE alleles were lower than those of patients harboring any of the minor variant alleles (p < 0.01). The 3-year survival time of AMI patients carrying the wild-type ACE alleles was markedly greater compared with AMI patients carrying the mutant genes (p < 0.01). Conclusion: Mutations at the ACE rs121912703, rs767880620, and rs397514689 loci affect the efficacy of perindopril on ventricular remodeling and hemodynamics in Chinese Han AMI patients. The 3-year survival of AMI patients harboring the variant alleles is less than that of the patients harboring the wild-type gene.


Assuntos
Infarto do Miocárdio/genética , Peptidil Dipeptidase A/genética , Perindopril/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Farmacológicos/sangue , China , Grupos Étnicos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Perindopril/metabolismo , Polimorfismo Genético/genética , Resultado do Tratamento
17.
Forensic Sci Int ; 299: 151-153, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31005711

RESUMO

In order to apply a useful STR system in DNA database construction, we performed a population study in China. Allele and genotype frequencies for STR SE33 were obtained for a sample of 213 random Chinese in view of application in personal identification. And we observed a new structural variation of 21.2 allele at SE33 locus which is described here for the first time.


Assuntos
Região 5'-Flanqueadora/genética , Alelos , Grupos Étnicos/genética , Genética Populacional , Repetições de Microssatélites , Mutação , China , Impressões Digitais de DNA , Frequência do Gene , Humanos , Análise de Sequência
18.
Genet Test Mol Biomarkers ; 23(5): 359-362, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30994363

RESUMO

Aim: The amelogenin gene is a widely used gender marker for forensic DNA profiling. Males who have the amelogenin Y (AMELY) allele deletion can be mistakenly identified as females if genotyping is performed only on the amelogenin gene. The aim of this study was to investigate the frequency of the AMELY allele deletion in the Chinese Han population and analyze the possible genetic variation on the Y chromosome. Materials and Methods: The amelogenin gene of 12,735 unrelated males from the Chinese Han population were genotyped using common forensic short tandem repeat (STR) kits. The AMELY allele deletion was verified by redesigned primers and sequencing. Eighteen Y-specific sequence tagged sites (STSs) on the Yp11.2 region were selected to delineate the deletion breakpoints on the Y chromosome. Results: Three males were confirmed to have no AMELY allele. The frequency rate of the AMELY-null allele was 0.236% (3/12,735) in the Chinese Han population of Central China; 2.73 Mb of sequence on the Y chromosome were absent in all the AMELY-negative samples. The deleted region was mapped using SRY, AMELY, 5 Y-STRs, and 18 STSs, which belong to the class I deleted pattern. The three unrelated males shared the same Y-STR haplotype with four males from other Chinese populations, all of whom have the AMELY-null allele. The haplogroup of these males was identified as the O3 haplogroup. Conclusion: The AMELY allele deletion in the Chinese population was accompanied by the deletion of the Y-STR loci on the Yp11.2 region. Therefore, another Y-specific marker should be tested simultaneously when unknown samples are examined as part of a criminal investigation.


Assuntos
Amelogenina/genética , Adulto , Alelos , Amelogenina/metabolismo , Amelogenina/fisiologia , Grupo com Ancestrais do Continente Asiático/genética , China , Cromossomos Humanos Y/genética , Impressões Digitais de DNA/métodos , Análise Mutacional de DNA/métodos , Grupos Étnicos/genética , Frequência do Gene/genética , Genótipo , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Fenótipo , Deleção de Sequência/genética , Análise para Determinação do Sexo/métodos
19.
Med Sci Monit ; 25: 2419-2428, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30940795

RESUMO

BACKGROUND Many studies have shown that hypertension may contribute to thoracic aortic dissection (TAD). Among the factors that modulate hypertension are endoplasmic reticulum stress and vascular smooth muscle cell proliferation which are in turn modulated by mitofusion-2 (Mfn2). Specifically, we determined, in the Han Chinese population, whether single nucleotide polymorphisms (SNPs) of Mfn2 influenced the occurrence of TAD. MATERIAL AND METHODS Six tagging SNPs of Mfn2 (rs2236057, rs3766741, rs2236058, rs17037564, rs2295281, and rs2336384) were genotyped using a TaqMan assay in 200 TAD patients and 451 health individuals from the Han Chinese population. RESULTS Logistic regression analysis indicated CC genotype of rs2295281 was highly linked to an increased risk of TAD (TT+CT versus CC, OR=0.540, 95% CI [0.320-0.911], P=0.021), implying that TT genotype and CT genotype of rs2295281 have a lower risk for TAD. Logistic regression analysis also indicated that rs2236058 was highly linked to the risk of TAD based on recessive genetic model, which indicated that the GG genotype was a protective factor against TAD (GG versus (CG+CC), OR=0.545, 95% CI [0.351-0.845], P=0.007). CG genotype and CC genotype of rs2236058 had a higher risk for TAD. In addition, rs2236058 was linked to the risk of TAD in the recessive genetic and homozygous models in the normotensive subgroup (GG versus (CG+CC), OR=0.298, 95% CI [0.112-0.792], P=0.015; GG versus CC, OR=0.528, 95% CI [0.302-0.925], P=0.026) but not in the hypertension subgroup. CONCLUSIONS Our findings showed that the occurrence of TAD in a Han Chinese population was influenced by Mfn2 polymorphisms.


Assuntos
Aneurisma Dissecante/genética , Aneurisma da Aorta Torácica/genética , GTP Fosfo-Hidrolases/genética , Proteínas Mitocondriais/genética , Adulto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Grupos Étnicos/genética , Feminino , GTP Fosfo-Hidrolases/fisiologia , Frequência do Gene/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
20.
Artigo em Inglês | MEDLINE | ID: mdl-31027310

RESUMO

Objective: This study was conducted to identify the association between rs4804803 polymorphism in DC-SIGN with the susceptibility of severe dengue. Methods: A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). Results: A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession (GG versus GA/AA: OR = 0.44, 95%CI, 0.23-0.82) and a codominant model (GG versus AA: OR = 0.43, 95%CI, 0.23-0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in rs4804803 was a risk factor for severe dengue under dominant (GG/GA versus AA: OR = 1.86,95%CI, 1.01-3.45), superdominant (GA versus GG/AA: OR = 1.81,95%CI, 1.02-3.21) and a codominant (GA versus AA: OR=1.82,95%CI, 1.02-3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive (GG versus GA/AA: OR = 0.27,95%CI, 0.10-0.70) and codominant (GG versus AA: OR=0.24,95%CI, 0.09-0.64) models. The results from subgroup analysis were robust. Conclusions: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) promoter-336G/A (rs4804803) polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Moléculas de Adesão Celular/genética , Vírus da Dengue/genética , Grupos Étnicos/genética , Lectinas Tipo C/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Receptores de Superfície Celular/genética , Dengue Grave/genética , China , Predisposição Genética para Doença , Humanos , Razão de Chances , Fatores de Risco , América do Sul
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