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1.
Fa Yi Xue Za Zhi ; 37(3): 358-365, 2021 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34379905

RESUMO

Abstract: Objective To study the genetic polymorphism of whole mitochondrial DNA (mtDNA) genomes in She population in Zhejiang and to explore the maternal genetic structure of the She population. Methods Whole mtDNA genomes of 231 unrelated individuals from She population in Zhejiang Province were sequenced. The number of mutations and population genetics parameters such as, the haplotype diversity (HD), discrimination power (DP), and random match probabilities (RMP) were analyzed. The mtDNA haplogroups of Zhejiang She population were classified, and the maternal genetic relationships between She and nine other Chinese populations were estimated. Results In 231 Zhejiang She samples, 8 507 mutations (702 types) were observed and the samples were classified into 94 haplogroups. The HD, DP and RMP values were 0.998 6, 0.994 2 and 0.005 8, respectively. The lowest genetic differentiation degree (Fst=0.006 89) was detected between Zhejiang She population and southern Han population. Principal component analysis (PCA) and median-joining network analysis showed that the genetic distance of Zhejiang She population with Guangxi Yao, Yunnan Dai and Southern Han populations was relatively close, but the population still had some unique genetic characteristics. Conclusion The whole mtDNA genomes are highly polymorphic in Zhejiang She population. The Zhejiang She population contains complex and diverse genetic components and has a relatively close maternal genetic relationship with Guangxi Yao, Yunnan Dai and Southern Han populations. Meanwhile, Zhejiang She population has kept its unique maternal genetic components.


Assuntos
DNA Mitocondrial , Sequenciamento de Nucleotídeos em Larga Escala , Grupo com Ancestrais do Continente Asiático/genética , China , DNA Mitocondrial/genética , Grupos Étnicos/genética , Feminino , Genética Populacional , Haplótipos , Humanos , Polimorfismo Genético
2.
Fa Yi Xue Za Zhi ; 37(3): 382-387, 2021 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34379909

RESUMO

Abstract: Objective To evaluate the discrimination efficiency of the SeqType® P52 Human Ancestry Identification SNP Detection Kit based on a high-throughput sequencing platform in five Chinese ethnic groups. Methods Using the SeqType® P52 Human Ancestry Identification SNP Detection Kit based on a high-throughput sequencing platform, a total of 350 samples from Han, Tibetan, Mongolian, Uygur, and Yi populations in China were detected and population cluster analysis was performed. Results The effective sequencing depth of a single site in a single sample was ≥720×, and the average report rate was 96%. The mean values of allele frequency differences between the Tibetan, Mongolian, Uygur, Yi and Han population were 0.20, 0.05, 0.24 and 0.11, respectively. Using Structure 2.3.4 software under K=5 mode, independent ancestral component in Han, Tibetan and Uygur could be detected, which was consistent with the result observed from the principal component analysis (PCA). For the Yi population, two thirds of them had relatively independent ancestral component close to the Tibetan population and one third were similar to the Uygur population. The Mongolian population had similar ancestral origin component with Han population. Conclusion The composite detection system with 52 screened ancestry-informative SNP sites has been established in this study, which can effectively analyze the composition and individual genetic components of populations from Han, Tibetan and Uygur. The ability to discriminate among Han, Mongolian and Yi needs to be further improved. The SeqType® P52 Human Ancestry Identification SNP Detection Kit can be used to infer the origin of an individual's ancestors in some forensic DNA cases.


Assuntos
DNA , Grupos Étnicos , Grupo com Ancestrais do Continente Asiático/genética , China , Grupos Étnicos/genética , Frequência do Gene , Genética Populacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Polimorfismo de Nucleotídeo Único
3.
J Headache Pain ; 22(1): 89, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380431

RESUMO

BACKGROUND: Considering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population. METHODS: We conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups. RESULTS: We discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM [Formula: see text] 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM. CONCLUSIONS: To our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis.


Assuntos
Estudo de Associação Genômica Ampla , Transtornos de Enxaqueca , Idade de Início , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Genótipo , Humanos , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Taiwan
4.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 225-229, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374231

RESUMO

Objective: To investigate the relationship between mitochondrial DNA (mtDNA) variation and high altitude essential hypertension(HAEH) in the Chinese Tajik population. Methods: Fifty-three patients with HAEH and 46 healthy subjects were enrolled from the Chinese Tajik population. The mtDNA fragments were amplificated by polymerase chain reaction, and products were sequenced to acquire full sequence of mtDNA. The mtDNA sequences of all subjects were compared to the Cambridge sequence to explore mtDNA variations and analyze difference between HAEH and healthy controls. Online softwares were applied to predict function changes caused by positive associated mtDNA variations. Results: Compared to the control group, the frequency of haplogroup U4b was significant higher in HAEH group(P=0.023,OR=7.062,CI(95%)=1.306-38.182), and the frequencies of 8 mutations from haplogroup U4b showed a significant difference between the HAEH group and control group (all with P values below 0.05). The mt DNA15693T>C mutation was the only missense mutation, which affected amino acid 316 in mitochondrial cytochrome b (MTCYB) by changing it from methionine to threonine. Bioinformatics analysis indicated that the mutation in MTCYB may play a biological role through affecting the second structure of protein. Conclusion: MtDNA subhaplogroup U4b is a genetic factor for HAEH in the Chinese Tajik population, and mtDNA15693T>C mutation may be an important molecular mechanism of HAEH.


Assuntos
DNA Mitocondrial , Predisposição Genética para Doença , Altitude , Grupo com Ancestrais do Continente Asiático/genética , China , DNA Mitocondrial/genética , Hipertensão Essencial/genética , Haplótipos , Humanos , Mutação
5.
Genome Biol Evol ; 13(8)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34302465

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing an unprecedented challenge to global public health. SARS-CoV-2 and several other coronaviruses utilize angiotensin-converting enzyme 2 (ACE2) as their entry receptors. The ACE2 gene has been found to experience episodic positive selection across mammals. However, much remains unknown about how the ACE2 gene evolved in human populations. Here, we use population genetics approaches to investigate the evolution of the ACE2 gene in 26 human populations sampled globally. We find the ACE2 gene exhibits an extremely low nucleotide diversity in the East Asian populations. Strong signals of selective sweep are detected in the East Asian populations, but not in the other human populations. The selective sweep in ACE2 is estimated to begin in East Asian populations ∼23,600 years ago. Our study provides novel insights into the evolution of the ACE2 gene within human populations.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Grupo com Ancestrais do Continente Asiático/genética , Evolução Molecular , Adaptação Fisiológica , DNA Antigo , Haplótipos , Humanos , Seleção Genética
6.
J Cancer Res Clin Oncol ; 147(10): 2935-2944, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34254208

RESUMO

PURPOSE: BRCA1/2 screening for all triple-negative breast cancer (TNBC) patients younger than 60 years may still be an economic burden in China. Further evidences that include incidence and outcome of BRCA1/2 pathogenic variants (PV) screened based on younger age or family history (FH) are worth discussing for improving the cost-effectiveness of BRCA1/2 testing in Chinese TNBC. We aimed to investigate the prevalence of germline and tumor BRCA1/2 PV based on age screening in Chinese TNBC patients. METHODS: Paired blood and tumor DNA from 124 unselected Chinese TNBC patients with less than or equal to 55 years were collected and analyzed for BRCA1/2 PV. Clinicopathological characteristics including age at diagnosis, FH and follow-up data were collected for further analysis. RESULTS: The entire frequency of germline and tumor BRCA1/2 PV was 21.0 and 25%, respectively. Among them, 20 (16.1%) germline and 5 (4.0%) somatic BRCA1/2 single-nucleotide variant/insertion/deletions were found by NGS testing, 6 (4.8%) BRCA1 large genomic rearrangements were detected in blood DNA by MPLA. There was significant correlation between FH of HBOC and germline BRCA1/2 PVs among these patients. Patients with tumor BRCA1/2 PVs had significant improvements than non-carriers in PFS (p = 0.047). No significant impacts were found between various mutation status in OS outcomes. No significant differences were found between BRCA1 or BRCA2 and non-carriers in PFS or OS. CONCLUSION: There is a high incidence of germline and tumor BRCA1/2 PVs in Chinese TNBC patients with less than or equal to 55 years old. Tumor BRCA1/2 PV carriers showed an improved survival outcome. Our results suggest that BRCA1/2 PVs testing addressed within each specific clinical scenario could be more cost-effective for patients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Neoplasias de Mama Triplo Negativas/patologia , Adolescente , Adulto , China/epidemiologia , Feminino , Seguimentos , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Adulto Jovem
7.
J Int Med Res ; 49(7): 3000605211019263, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34275374

RESUMO

OBJECTIVE: To investigate the relationship between angiotensin (AGT) rs2493132 gene polymorphism and the risk of developing non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population. METHODS: Polymerase chain reaction was performed to determine AGT genotypes. Anthropometric and clinical data were investigated and statistically analyzed in the clinical laboratory department of Qingdao Municipal Hospital. RESULTS: The AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD and NAFLD + CAD in healthy controls. The AGT rs2493132 T allele increased the risk of NAFLD + CAD in healthy controls. The AGT rs2493132 CT + TT genotype and T allele also significantly increased the risk of CAD in patients with NAFLD after adjustments for age, sex, and body mass index. In addition, AGT rs2493132 T allele carriers showed higher total cholesterol (TC) and low-density lipoprotein (LDL) levels compared with non-carriers. CONCLUSIONS: The AGT rs2493132 CT + TT genotype and T allele significantly increased the risk of developing CAD in patients with NAFLD in the Chinese Han population. The AGT rs2493132 T allele was associated with increased serum TC and LDL levels.


Assuntos
Doença da Artéria Coronariana , Hepatopatia Gordurosa não Alcoólica , Angiotensinogênio , Angiotensinas , Grupo com Ancestrais do Continente Asiático/genética , China , Doença da Artéria Coronariana/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
8.
Eur J Endocrinol ; 185(4): 441-451, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34288885

RESUMO

Objective,: To investigate the genetic characteristics of idiopathic central precocious puberty (ICPP) and validate its polygenic risk for early puberty. Design and methods: A bootstrap subsampling and genome-wide association study were performed on Taiwanese Han Chinese girls comprising 321 ICPP patients and 148 controls. Using previous GWAS data on pubertal timing, a replication study was performed. A validation group was also investigated for the weighted polygenic risk score (wPRS) of the risk of early puberty. Results: A total of 105 SNPs for the risk of ICPP were identified, of which 22 yielded an area under the receiver operating characteristic curve of 0.713 for the risk of early puberty in the validation group. A replication study showed that 33 SNPs from previous GWAS data of pubertal timing were associated with the risk of ICPP (training group: P-value < 0.05). In the validation group, a cumulative effect was observed between the wPRS and the risk of early puberty in a dose-dependent manner (validation group: Cochran-Armitage trend test: P-value < 1.00E-04; wPRS quartile 2 (Q2) (odds ratio (OR) = 5.00, 95% CI: 1.55-16.16), and wPRS Q3 (OR = 11.67, 95% CI: 2.44-55.83)). Conclusions: This study reveals the ICPP genetic characteristics with 22 independent and 33 reported SNPs in the Han Chinese population from Taiwan. This study may contribute to understand the genetic features and underlying biological pathways that control pubertal timing and pathogenesis of ICPP and also to the identification of individuals with a potential genetic risk of early puberty.


Assuntos
Herança Multifatorial , Puberdade Precoce/genética , Idade de Início , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Heterogeneidade Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Puberdade/genética , Puberdade Precoce/epidemiologia , Fatores de Risco , Taiwan/epidemiologia
9.
Anticancer Res ; 41(8): 3997-4004, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281864

RESUMO

BACKGROUND/AIM: The frequency of somatic mutations of epidermal growth factor receptor (EGFR) in primary lung adenocarcinoma varies among populations and countries. The aim of the present study was to clarify whether the frequency of EGFR mutations in patients with lung adenocarcinoma depends on their mitochondrial DNA haplogroup, which reflects their maternal lineage. PATIENTS AND METHODS: Using normal lung tissue specimens, the mitochondrial DNA haplogroup was determined by multiplex polymerase chain reaction in 135 Japanese patients who underwent surgery for primary lung adenocarcinoma. RESULTS: The 135 patients were divided into two groups according to the two primitive haplotypes (N group, n=32; M group, n=103). The frequency of EGFR mutations in the N group was significantly higher than that in the M group (69% vs. 48%, p=0.044). The difference was prominent when the analysis was restricted to non-smokers (95% vs. 57%, p<0.01). CONCLUSION: The frequency of EGFR mutations in lung adenocarcinoma patients depends on their mitochondrial lineage.


Assuntos
Adenocarcinoma de Pulmão/genética , Grupo com Ancestrais do Continente Asiático/genética , DNA Mitocondrial , Neoplasias Pulmonares/genética , Idoso , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fumar/genética
10.
J Int Med Res ; 49(7): 3000605211029504, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34266338

RESUMO

OBJECTIVE: Schizophrenia is a complex mental disorder with high heritability. The hypothalamic-pituitary-adrenal (HPA) axis, which is the stress system of the neuroendocrine system, is considered to impact psychotic disorders. We hypothesized that polymorphisms of HPA axis genes might be involved in the development of schizophrenia. METHODS: A case-control study comprising 234 patients with schizophrenia and 399 matched healthy controls was conducted to investigate the association between the human melanocortin 2 receptor (MC2R) gene and schizophrenia risk. Seven tag single nucleotide polymorphisms (SNPs) (rs16941303, rs16941314, rs2186944, rs28926188, rs7230126, rs948322, and rs948331) of MC2R were genotyped by direct sequencing. RESULTS: No significant associations were observed between any of the alleles, genotypes, or haplotypes examined within the MC2R gene and the risk of schizophrenia in the total group or in subgroups stratified by smoking or alcoholism. However, a subgroup analysis stratified by sex revealed that under the additive model, the C allele of the MC2R rs948331 SNP significantly decreased the risk of schizophrenia in females (odds ratio=0.18). CONCLUSION: The C allele of the MC2R rs948331 locus may be a protective factor, reducing the risk of schizophrenia in the female Han Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático , Receptor Tipo 2 de Melanocortina , Esquizofrenia , Regiões 3' não Traduzidas , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 2 de Melanocortina/genética , Receptor Tipo 2 de Melanocortina/metabolismo , Esquizofrenia/genética
11.
Aging (Albany NY) ; 13(13): 17237-17252, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34214049

RESUMO

Genetic background has been considered one of the important contributors to the rate of cognitive decline among patients with Alzheimer's disease (AD). We conducted a 4-year longitudinal follow-up study, recruited 255 AD and 44 mild cognitive impairment (MCI) patients, and used a data-driven trajectory analysis to examine the influence of selected AD risk genes on the age for and the rate of cognitive decline in Han Chinese population. Genotyping of selected single-nucleotide polymorphisms in the APOE, ABCA7, SORL1, BIN1, GAB2, and CD33 genes was conducted, and a Bayesian hierarchical model was fitted to analyze the trajectories of cognitive decline among different genotypes. After adjusting for sex and education years, the APOE ε4 allele was associated with an earlier mean change of -2.39 years in the age at midpoint of cognitive decline, the G allele in ABCA7 rs3764650 was associated with an earlier mean change of -1.75 years, and the T allele in SORL1 rs3737529 was associated with a later mean change of 2.6 years. Additionally, the rate of cognitive decline was associated with the APOE ε4 allele and SORL1 rs3737529. In summary, APOE and SORL1 might be the most important genetic factors related to cognitive decline in Han Chinese population.


Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Grupo com Ancestrais do Continente Asiático/genética , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Feminino , Seguimentos , Genótipo , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Estudos Longitudinais , Masculino , Proteínas de Membrana Transportadoras/genética , Testes de Estado Mental e Demência , Polimorfismo de Nucleotídeo Único , Taiwan/epidemiologia
12.
Gene ; 800: 145838, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34274472

RESUMO

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwide. It accounts for approximately 30 ~ 40% of glomerular diseases in China. However, the exact pathogenesis of IgAN is not well established. This study aimed to explore the association between MIR17HG polymorphisms and IgAN susceptibility. METHODS: Six single nucleotide polymorphisms (SNPs) of MIR17HG were genotyped in 417 patients with IgAN and 424 healthy controls. The association analysis was conducted by logistic regression adjusted for age and gender in multiple genetic models and different subgroups. RESULTS: Our results revealed that rs72640334 and rs1428 increased the susceptibility to IgAN in total populations (p < 0.05). The stratification analysis by age indicated that rs72640334 enhanced the risk of IgAN people older than 35 years, while rs7318578 played a protective role in the development of IgAN patients aged >35 years (p < 0.05). In addition, MIR17HG-rs72640334 could facilitate the occurrence of IgAN in females (p < 0.05). In Lee's grade III-Vsubgroup, rs72640334 and rs7336610 have an increasing effect on IgAN risk, while rs7318578 has a decreasing effect on IgAN susceptibility (p < 0.05). CONCLUSIONS: Our findings suggested that MIR17HG genetic polymorphisms were correlated with IgAN susceptibility. It provided new evidence for the potential molecular mechanism of IgAN and may serve as a new biomarker for the treatment and early diagnosis of IgAN.


Assuntos
Glomerulonefrite por IGA/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos
13.
Gene ; 800: 145832, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34274476

RESUMO

OBJECTIVE: To investigate the association of FOXO3a polymorphisms and ankylosing spondylitis (AS) susceptibility in Eastern Chinese Han population. METHODS: FOXO3a polymorphisms rs12206094, rs12212067, rs2253310, rs3800232, and rs4946933 were genotyped in 650 AS patients and 646 controls by the improved Multiple Ligase Detection Reaction. RESULTS: The distribution of genotype in rs12212067 polymorphism was significantly different between AS patients and controls (P = 0.020), especially in male population (P = 0.009). There was significant difference of the genotype frequency distribution at rs3800232 between patients and controls in male population. The results of binary regression analysis showed that the rs12212067 GG genotype and rs3800232 TT genotype were obviously correlated with elevated AS risk, and the associations were still significant after being adjusted by age and gender (all P < 0.05). Interestingly, rs12212067 and rs3800232 genotypes were associated with disease activity of patients. Additionally, haplotype block rs12212067G- rs3800232T (OR = 1.403, 95%CI = 1.011-1.949) was further shown to confer promoting effect on developing AS. CONCLUSION: Among Eastern Chinese Han population, FOXO3a polymorphism rs12212067 and rs3800232 may contribute to increased risk of developing AS, but well-designed multicenter studies are needed to further confirm these preliminary findings in the future.


Assuntos
Proteína Forkhead Box O3/genética , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Espondilite Anquilosante/etiologia
14.
Gene ; 800: 145834, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34274483

RESUMO

Hepatoblastoma is the most common malignant liver cancer in childhood, yet its etiology remains unclear. As an m6A methylation modifier, methyltransferase like 3 (METTL3) has an active methyltransferase domain that functionally participates in various tumor occurrence and development. However, little is known about how METTL3 polymorphisms affect the occurrence of hepatoblastoma. Here, we attempted to investigate the associations between METTL3 gene polymorphisms and hepatoblastoma risk in a seven-center case-control study. We genotyped four METTL3 polymorphisms (rs1061026 T > G, rs1061027 C > A, rs1139130 A > G, rs1263801 G > C) by TaqMan technique in 313 cases and 1446 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the contributions of these four single nucleotide polymorphisms (SNPs) to hepatoblastoma susceptibility. In single genotype analysis, we detected no significant correlation between these four polymorphisms in METTL3 and hepatoblastoma risk. However, in the combined analysis, the presence of 2-4 risk genotypes of METTL3 was associated with an increased risk of hepatoblastoma compared with that of 0-1 risk genotypes (adjusted OR = 1.48, 95% CI = 1.03-2.12, P = 0.035). The stratified analysis further revealed that carriers of 2-4 risk genotypes are more susceptible to hepatoblastoma in the subgroups of subjects aged under 17 months (adjusted OR = 1.88, 95% CI = 1.12-3.16, P = 0.016) and females (adjusted OR = 1.79, 95% CI = 1.06-3.05, P = 0.031). Overall, our results revealed that none of these four SNPs could increase susceptibility to hepatoblastoma individually. Carriers with 2-4 risk genotypes in the combined analysis tend to increase the risk of hepatoblastoma.


Assuntos
Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Pré-Escolar , Frequência do Gene , Predisposição Genética para Doença , Humanos , Lactente
15.
J Int Med Res ; 49(7): 3000605211033219, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34311603

RESUMO

OBJECTIVE: To investigate whether GSTA1, GSTO2, and GSTZ1 are relevant to an increased risk of amyotrophic lateral sclerosis (ALS) in a Chinese population. METHODS: In this study, 143 sporadic ALS (sALS) patients (83 men, 60 women) and 210 age- and sex-matched healthy subjects were enrolled. Blood samples were collected by venipuncture. Genomic DNA was isolated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) according to the manufacturer's instructions. The potential associations between ALS and GSTA1, GSTO2, and GSTZ1 polymorphisms were estimated using chi-squared analysis and unconditional logistic regression. RESULTS: The D allele and genotype frequencies of GSTO2 were increased in sALS patients compared with healthy subjects, indicating that the GSTO2 DD genotype was associated with an increased risk of sALS (odds ratio [OR] = 3.294, 95% confidence interval [CI] = 1.039-10.448). However, a significant association between the DD genotype and the risk of sALS was evident in men only (OR = 7.167, 95% CI = 1.381-37.202). CONCLUSION: This study revealed that the D allele and genotype frequencies of GSTO2 were increased in sALS patients. The GSTO2 DD genotype was associated with an increased risk of sALS in men in a Chinese population.


Assuntos
Esclerose Amiotrófica Lateral , Predisposição Genética para Doença , Glutationa Transferase , Esclerose Amiotrófica Lateral/genética , Grupo com Ancestrais do Continente Asiático/genética , China , Feminino , Genótipo , Glutationa Transferase/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
16.
Genes (Basel) ; 12(7)2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202464

RESUMO

ABO blood system is an inborn trait determined by the ABO gene. The genetic-phenotypic mechanism underneath the four mutually exclusive and collectively exhaustive types of O, A, B and AB could theoretically be elucidated. However, genetic polymorphisms in the human populations render the link elusive, and importantly, past studies using genetically determined rather than biochemically determined ABO types were not and could not be evaluated for the inference errors. Upon both blood-typing and genotyping a cohort of 1008 people of the Han Chinese population, we conducted a genome-wide association study in parallel with both binomial and multinomial log-linear models. Significant genetic variants are all mapped to the ABO gene, and are quantitatively evaluated for binary and multi-class classification performances. Three single nucleotide polymorphisms of rs8176719, rs635634 and rs7030248 would together be sufficient to establish a multinomial predictive model that achieves high accuracy (0.98) and F1 scores (micro 0.99 and macro 0.97). Using the set of identified ABO-associated genetic variants as instrumental variables, we demonstrate the application in causal analysis by Mendelian randomization (MR) studies on blood pressures (one-sample MR) and severe COVID-19 with respiratory failure (two-sample MR).


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Sistema ABO de Grupos Sanguíneos/genética , COVID-19/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Pressão Sanguínea/genética , COVID-19/etiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Modelos Estatísticos , Testes Sorológicos
18.
Medicine (Baltimore) ; 100(25): e24691, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160378

RESUMO

ABSTRACT: Branchio-Oto (BO) syndrome is one of the common syndromic forms of hearing loss. In this study, we aimed to characterize the clinical and genetic features of BO syndrome in a Chinese deaf family.The proposita in this study was a 29-years-old Chinese female with hearing loss, microtia, anterior concave auricle, and right branchial fistula. The family members agreed to undergo clinical examination. We collected blood samples from 7 family members, including 4 affected by the syndrome. Genomic DNA was extracted and subjected to Sanger sequencing. In addition, bioinformatics software SWISS MODEL was used to predict the protein encoded by EYA transcriptional coactivator and phosphatase 1 (EYA1) gene.Intra-familial consistency can be observed in the clinical phenotypes of BO syndrome in this family. EYA1 c.1627C>T (p.Gln543Ter) mutation was identified as the pathogenic cause in this family.This study reports a mutation associated with BO syndrome in a Chinese Han family. We highlight the utility of genetic testing in the diagnosis of BO syndrome. Thus, we believe that this report would provide a basis for the diagnosis of similar diseases in the future.


Assuntos
Síndrome Brânquio-Otorrenal/genética , Microtia Congênita/genética , Perda Auditiva/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Proteínas Tirosina Fosfatases/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Audiometria , Síndrome Brânquio-Otorrenal/diagnóstico , Criança , Biologia Computacional , Microtia Congênita/diagnóstico , Análise Mutacional de DNA , Feminino , Testes Genéticos , Perda Auditiva/congênito , Perda Auditiva/diagnóstico , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Linhagem
19.
J Stroke Cerebrovasc Dis ; 30(8): 105674, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34119749

RESUMO

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is caused by the Notch3 gene mutation, has its unique clinical and imaging characteristics. Here we present a Chinese family with a novel mutation on exon 10 of Notch3 gene. METHODS: Clinical and MRI data of the three patients in the family during the 7-year follow-up were collected. The CADASIL Scale Score was calculated to evaluate the disease risk of the three patients at their first admission or clinic visit. Five family members underwent genetic test. RESULTS: Genetic test confirmed the diagnosis of CADASIL in this family. A novel mutation of p.C533S on exon 10 of Notch3 gene was detected. The CADASIL score of the proband and her sister was both 17 and that of her brother was 14. CONCLUSIONS: Our report not only expands the mutation spectrum of Notch3 gene in CADASIL, but also shows the distinct heterogeneity of CADASIL patients in the same family with the same mutation.


Assuntos
CADASIL/genética , Mutação de Sentido Incorreto , Receptor Notch3/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , CADASIL/diagnóstico , CADASIL/etnologia , China , Análise Mutacional de DNA , Éxons , Feminino , Predisposição Genética para Doença , Hereditariedade , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo
20.
Sci Rep ; 11(1): 12346, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117310

RESUMO

With the growing evidence on the variable human susceptibility against COVID-19, it is evident that some genetic loci modulate the severity of the infection. Recent studies have identified several loci associated with greater severity. More recently, a study has identified a 50 kb genomic segment introgressed from Neanderthal adding a risk for COVID-19, and this genomic segment is present among 16% and 50% people of European and South Asian descent, respectively. Our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations, respectively, which appears to be responsible for the low case fatality rate among South Asian populations. This result was also consistent with the real-time infection rate and case fatality rate among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the real-time infection rates and case fatality rate in India. We found that the polymorphism present in the 50 kb introgressed genomic segment (rs10490770) did not show any significant correlation with the infection and case fatality rate in India.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , COVID-19/patologia , Enzima de Conversão de Angiotensina 2/genética , COVID-19/virologia , Frequência do Gene , Loci Gênicos , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , SARS-CoV-2/isolamento & purificação
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