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1.
Medicine (Baltimore) ; 100(15): e24523, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847607

RESUMEN

BACKGROUND: Infertility affects childbearing age couples all over the world. One of the important reasons for infertility is genetic factors. Our study evaluated the association between methylenetetrahydrofolate reductase (MTHFR) and azoospermia. METHODS: Multiple databases like MEDLINE, EMBASE, Cochrane library, and China journal full-text database were used to search for relevant studies, and full-text articles involved in the evaluation of MTHFR and azoospermia. The results were evaluated using STATA 12.0. Heterogeneity analysis, sensitivity analysis, and bias analysis were also performed on the data. RESULTS: Thirteen related studies eventually met the inclusion criteria. Significant association between C677T polymorphism and azoospermia (relative risk [RR] = 0.94 [0.90, 0.99], I2 = 60.9%, P = .002), and between A1298C polymorphism and azoospermia (RR = 0.98 [0.94, 1.02], I2 = 56.3%, P = .011) was observed. Meanwhile, in subgroup analysis, Caucasians had higher risk than Mongolians in association between MTHFR and azoospermia. CONCLUSION: There was association between MTHFR polymorphism and azoospermia. Caucasian populations had higher risk than Mongolian populations in association between MTHFR and azoospermia.


Asunto(s)
Azoospermia/genética , Predisposición Genética a la Enfermedad/etnología , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Grupo de Ascendencia Continental Asiática/genética , Grupo de Ascendencia Continental Europea/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Factores de Riesgo
2.
J Int Med Res ; 49(4): 3000605211006522, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33823642

RESUMEN

OBJECTIVE: To explore the relationship between the omentin-1 gene rs2274907 A>T polymorphism and colorectal cancer (CRC) in the Chinese Han population. METHODS: rs2274907 A>T was assessed by PCR-restriction fragment length polymorphism analysis. Plasma omentin-1 expression from 358 patients with CRC and 286 healthy controls was analyzed by enzyme-linked immunosorbent assay. CRC and control groups were divided into subgroups according to the body mass index (BMI) threshold of 25 kg/m2. RESULTS: No significant differences were observed between CRC and control groups in terms of genotype or allele frequencies of rs2274907 A>T. Compared with individuals with BMI <25 kg/m2 and the rs2274907 TT genotype, those with AA+AT genotypes and BMI ≥25 kg/m2 had a 3.027-fold increased risk of CRC. A significant tendency toward a higher stage of colorectal adenocarcinomas and depth of invasion was observed in individuals with the rs2274907 AA genotype compared with other genotypes. CONCLUSIONS: The omentin-1 gene rs2274907 A>T polymorphism does not seem to play a critical role in the development of CRC in the Chinese Han population, but an interaction between the rs2274907 A allele and BMI may increase the CRC risk. The rs2274907 AA genotype is a potential biomarker for CRC stage progression.


Asunto(s)
Neoplasias Colorrectales , Citocinas , Lectinas , Polimorfismo de Nucleótido Simple , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , China , Neoplasias Colorrectales/genética , Citocinas/genética , Femenino , Proteínas Ligadas a GPI/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lectinas/genética , Masculino , Polimorfismo de Nucleótido Simple/genética
3.
Medicine (Baltimore) ; 100(17): e25487, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907097

RESUMEN

BACKGROUD: To analyze the correlation between gene polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR) and risk of unexplained recurrent pregnancy loss (URPL) in Chinese women. METHODS: Eligible studies were searched in Pubmed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Established inclusion criteria were used to screening articles, subsequently evaluate the quality of the included studies, Stata 16.0 PM and RevMan 5.3 software were conducted for meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between MTHFR and risk of URPL in Chinese women. RESULTS: For MTHFR C677T, fifty studies were included, involving 6677 URPL cases and 8111 controls. The overall results showed that MTHFR C677T was significantly correlated with URPL risk, especially in the homozygous model (TT vs CC; OR 3.06; 95% CI 2.56-3.66). For MTHFR A1298C, twenty-first studies were included, involving 3439 URPL cases and 3155 controls. The results showed that MTHFR A1298C was also significantly correlated with URPL risk in recessive (CC vs AC + AA; OR 1.55; 95% CI 1.25-1.93) and homozygous (CC vs AA; OR 1.53; 95% CI 1.22-1.91) models. In addition, sub-group results showed that no significant difference between north and south China populations in the MTHFR gene polymorphisms and URPL risk. Of note, the patients carrying MTHFR C677T and MTHFR A1298C joint mutants had no synergistic effect (OR 2.71; 95% CI 0.84-8.70) on the occurrence of URPL compared with the wild-type homozygous genotype (MTHFR 677CC/ MTHFR 1298AA). CONCLUSION: Studies included in this meta-analysis suggested that MTHFR 677T allele and 677TT genotype and MTHFR 1298CC genotype were both associated with URPL; testing MTHFR C677T gene polymorphism was a more appropriate target compared with other mutations in the prediction of URPL.


Asunto(s)
Aborto Habitual/genética , Predisposición Genética a la Enfermedad/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Aborto Habitual/etnología , Adulto , Alelos , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , China , Femenino , Genotipo , Humanos , Oportunidad Relativa , Embarazo , Factores de Riesgo
4.
Medicine (Baltimore) ; 100(17): e25647, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907123

RESUMEN

ABSTRACT: To understand the possible carrier status of genes associated with hereditary hearing loss (HHL) in the general population among local residents and to give genetic counseling for pregnant women.A total of 3541 subjects were recruited. We used multiplex PCR technology combined with next-generation sequencing technology to detect 100 hotspot mutations in 18 common deafness-related genes. The homozygous mutation screening results were verified using Sanger sequencing.Of the 3541 participants, 37 alleles of 8 deafness genes were detected. A total of 145 (4.09%) were found to be GJB2 gene mutation carriers, and the hotspot mutation was c.235delC (1.54%). Twenty three (0.65%) were found to be GJB3 gene mutation carriers. A total of 132 (3.37%) were found to be SLC26A4 gene mutation carriers, and the hotspot mutation was c.919-2A > G (0.49%). Forty four (1.24%) were found to be mitochondrial DNA mutation carriers. Sanger sequencing results verified that 2 cases were homozygous for the c.235delC mutation and that 1 case was homozygous for the c.754T > C mutation.Genetic testing for pregnant women and their partners allows early identification of the molecular etiology of hearing loss (HL). On the one hand, it could give genetic counseling for pregnant women, such as early diagnosis of delayed deafness and drug-susceptible deafness. On the other hand, it could be used to assess hearing conditions during pregnancy, leading to prevention and timely intervention for newborns.


Asunto(s)
Pruebas Genéticas/métodos , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/genética , Diagnóstico Prenatal/métodos , Adulto , Alelos , Grupo de Ascendencia Continental Asiática/genética , China , Conexina 26/genética , Conexinas/genética , Análisis Mutacional de ADN , ADN Mitocondrial/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Recién Nacido , Masculino , Proteínas de la Membrana/genética , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Embarazo , Transportadores de Sulfato/genética
5.
BMC Cancer ; 21(1): 391, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836687

RESUMEN

BACKGROUND: Astrocytoma is a common type of central nervous system tumor. In this study, we investigated the correlation between ST6GAL1 and CYP19A1 polymorphisms and the risk and prognosis of astrocytoma. METHODS: A total of 365 astrocytoma patients and 379 healthy controls were genotyped using the Agena MassARRAY system. The correlation between ST6GAL1 and CYP19A1 variants and astrocytoma risk was calculated using logistic regression. The survival rate of patients with astrocytoma was analyzed to evaluate prognosis. RESULTS: We found that the ST6GAL1-rs2239611 significantly decreased the risk of astrocytoma in the codominant model (p = 0.044) and dominant model (p = 0.049). In stratified analyses, CYP19A1-rs2255192 might be associated with a higher risk of astrocytoma among the low-grade subgroup under recessive (p = 0.034) and additive (p = 0.030) models. However, CYP19A1-rs4646 had a risk-decreasing effect on the high-grade subgroup in the codominant model (p = 0.044). The results of Cox regression analysis showed that the CYP19A1-rs2239611 and -rs1042757 polymorphisms were significantly correlated with the prognosis of astrocytoma. CONCLUSION: Our results suggest that ST6GAL1 and CYP19A1 genes may be a potential biomarker of genetic susceptibility and prognosis to astrocytoma in the Chinese Han population.


Asunto(s)
Regiones no Traducidas 3' , Antígenos CD/genética , Aromatasa/genética , Astrocitoma/epidemiología , Astrocitoma/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Sialiltransferasas/genética , Adulto , Alelos , Grupo de Ascendencia Continental Asiática/genética , Astrocitoma/mortalidad , Astrocitoma/terapia , Estudios de Casos y Controles , China/epidemiología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia
6.
Medicine (Baltimore) ; 100(16): e25463, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879678

RESUMEN

INTRODUCTION: Wilson Disease (WD) is an autosomal recessive inherited metabolic disease caused by mutations in the ATPase copper transporting beta gene (ATP7B). WD can cause fatal neurological and hepatic disorders if not diagnosed and treated. OBJECTIVE: To analyze the disease-causing mutations of 14 Chinese WD children, 11 of whom are diagnosed with hepatic disorders, 2 with neurological degeneration and 1 with both hepatic and neurological disorders. METHODS: All ATP7B coding regions were analyzed by Sanger sequencing. Single nucleotide polymorphisms (SNPs) functional impacts were assessed by combining the results of four bioinformatics tools (Poly-phen-2, SIFT, PANTHER-PSEP and PhD-SNPs) in an index that reflects the combined probability (cPdel) of an amino acid change to be deleterious to the protein function. RESULTS: Two novel variants involved in WD development, c.1448_1455del (p.Arg483SerfsX19) and c.4144G>T (p.Glu1382Stop), and 11 previously reported mutations were detected. Both new variants result in shortened and dysfunctional ATP7B proteins. cPdel score suggests that SNPs may be deleterious to the ATP7B functionality. CONCLUSIONS: This study enriches the library of the ATP7B mutations that lead to WD and can be used as a basis for genetic counseling, for WD prevention and clinical and prenatal diagnosis. Those SNPs that are believed to be harmless to ATP7B protein may be involved in the pathogenesis of WD.


Asunto(s)
ATPasas Transportadoras de Cobre/genética , Degeneración Hepatolenticular/genética , Grupo de Ascendencia Continental Asiática/genética , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Asesoramiento Genético , Pruebas Genéticas , Degeneración Hepatolenticular/sangre , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/prevención & control , Humanos , Masculino , Mutación , Polimorfismo de Nucleótido Simple
7.
Medicine (Baltimore) ; 100(16): e25527, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879693

RESUMEN

RATIONALE: Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities. PATIENT CONCERNS: Patient 1, a 13-day-old male newborn of the Chinese Lahu minority, showed a classic WAS phenotype, including thrombocytopenia, small platelets, buttock eczema, and recurrent infections. Patient 2, an 8-year-and 8-month-old boy of the Chinese Zhuang minority, presented an XLT phenotype without eczema and repeated infections. DIAGNOSIS: Next-generation sequencing was performed to investigate the genetic variations. Flow cytometry was used to quantify the expression of WAS protein and analyze the lymphocyte subsets. A novel frameshift WAS mutation (c.927delC, p.Q310Rfs∗135) and a known nonsense WAS mutation (c.1090C>T, p.R364X) were identified in Patient 1 and Patient 2, respectively. Both patients were confirmed to have WAS protein deficiency, which was more severe in Patient 1. Meanwhile, the analysis of lymphocyte subsets revealed an abnormality in Patient 1, but not in Patient 2. Combined with the above clinical data and genetic characteristics, Patient 1 and Patient 2 were diagnosed as classic WAS and XLT, respectively. In addition, many miliary nodules were accidentally found in abdominal cavity of Patient 2 during appendectomy. Subsequently, Patient 2 was confirmed with pulmonary and abdominal tuberculosis through further laboratory and imaging examinations. To our knowledge, there have been only a few reports about WAS/XLT with tuberculosis. INTERVENTIONS: Both patients received anti-infection therapy, platelet transfusions, and intravenous immunoglobulins. Moreover, Patient 2 also received antituberculosis treatment with ethambutol and amoxicillin-clavulanate. OUTCOMES: The clinical symptoms and hematological parameters of these 2 patients were significantly improved. Regrettably, both patients discontinued the treatment for financial reasons. LESSONS: Our report expands the pathogenic mutation spectrum of WAS gene and emphasizes the importance of molecular genetic testing in diagnosing WAS. Furthermore, researching and reporting rare cases of WAS from different populations will facilitate diagnosis and treatment of this disease.


Asunto(s)
Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Trombocitopenia/diagnóstico , Proteína del Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/diagnóstico , Grupo de Ascendencia Continental Asiática/genética , Niño , Análisis Mutacional de ADN , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Recién Nacido , Masculino , Grupos Minoritarios , Trombocitopenia/genética , Síndrome de Wiskott-Aldrich/genética
8.
Medicine (Baltimore) ; 100(15): e25530, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847678

RESUMEN

OBJECTIVE: The present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension. METHODS: PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or ß and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software. RESULTS: A total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10-1.28; rs2681472: OR = 1.15, 95%CI: 1.12-1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, ß=1.01, 95%CI: 0.86-1.16, DBP, ß=0.48, 95%CI: 0.30-0.66; rs2681472: SBP, ß=0.92, 95%CI: 0.77-1.07, DBP, ß=0.50, 95%CI: 0.42-0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13-1.20) than in East Asians (OR = 1.14, 95%CI: 1.10-1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10-1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10-1.17). CONCLUSIONS: Our study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.


Asunto(s)
Presión Sanguínea/genética , Predisposición Genética a la Enfermedad/genética , Hipertensión/genética , ATPasas Transportadoras de Calcio de la Membrana Plasmática/genética , Polimorfismo Genético/genética , Adulto , Grupo de Ascendencia Continental Asiática/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo
9.
Medicine (Baltimore) ; 100(11): e25169, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33726005

RESUMEN

RATIONALE: X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is a rare hereditary cause in childhood short stature due to mutations in trafficking protein particle complex subunit 2 (TRAPPC2) gene located on chromosome Xp22. Several pathogenic variants in TRAPPC2 have been reported, but missense variants are rare. PATIENT CONCERNS: A 13-year, 8-month-old Chinese Han boy presenting with short stature for the past 7 years. DIAGNOSIS: X-linked SEDT was established by a combination of clinical and radiographic features, confirmed by targeted next-generation sequencing. Genetic testing of the TRAPPC2 gene revealed a novel missense variant with c.260A>C (p.H87P) hemizygote in exon5. The mother was found to be a heterozygous TRAPPC2 carrier, whereas the father was normal. INTERVENTIONS: Patient was treated with recombinant human growth hormone daily. Patient's height, glucose level, and possible progressive joint and back pain with osteoarthritis were under intensive observation regularly. OUTCOMES: The patient achieved 2.1 cm height gain over the first 3 months' recombinant human growth hormone treatment without joint or back pain. However, the therapy was terminated because of increased glucose level on follow-up. LESSONS: The short stature is a noteworthy problem for X-linked SEDT cases. We report a novel missense variant site in TRAPPC2 treated with growth hormone in the literature. We do not recommend the use of recombinant human growth hormone on patients with X-linked SEDT for the concern of glucose homeostasis.


Asunto(s)
Enfermedades Genéticas Ligadas al Cromosoma X/genética , Proteínas de Transporte de Membrana/genética , Mutación Missense/genética , Osteocondrodisplasias/genética , Factores de Transcripción/genética , Adolescente , Grupo de Ascendencia Continental Asiática/genética , Humanos , Masculino
10.
Am J Hum Genet ; 108(4): 632-655, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33770506

RESUMEN

The development of polygenic risk scores (PRSs) has proved useful to stratify the general European population into different risk groups. However, PRSs are less accurate in non-European populations due to genetic differences across different populations. To improve the prediction accuracy in non-European populations, we propose a cross-population analysis framework for PRS construction with both individual-level (XPA) and summary-level (XPASS) GWAS data. By leveraging trans-ancestry genetic correlation, our methods can borrow information from the Biobank-scale European population data to improve risk prediction in the non-European populations. Our framework can also incorporate population-specific effects to further improve construction of PRS. With innovations in data structure and algorithm design, our methods provide a substantial saving in computational time and memory usage. Through comprehensive simulation studies, we show that our framework provides accurate, efficient, and robust PRS construction across a range of genetic architectures. In a Chinese cohort, our methods achieved 7.3%-198.0% accuracy gain for height and 19.5%-313.3% accuracy gain for body mass index (BMI) in terms of predictive R2 compared to existing PRS approaches. We also show that XPA and XPASS can achieve substantial improvement for construction of height PRSs in the African population, suggesting the generality of our framework across global populations.


Asunto(s)
Estatura/genética , Índice de Masa Corporal , Simulación por Computador , Modelos Genéticos , Herencia Multifactorial/genética , África/etnología , Grupo de Ascendencia Continental Africana/genética , Grupo de Ascendencia Continental Asiática/genética , China/etnología , Bases de Datos Factuales , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Análisis de Componente Principal , Tamaño de la Muestra , Reino Unido
11.
Medicine (Baltimore) ; 100(10): e24161, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725819

RESUMEN

ABSTRACT: Propionic acidemia is associated with pathogenic variants in PCCA or PCCB gene. We investigated the potential pathogenic variants in PCCA or PCCB genes in Fujian Han population.Two probands and their families of Han ethnicity containing two generations were subject to newborn screening using tandem mass spectrometry, followed by diagnosis using urine gas chromatography mass spectrometry. Sanger sequencing was used to identify potential mutations in PCCA and PCCB genes.Compound heterozygous variants were identified in PCCB gene in two siblings of the first family, the youngest girl showed a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 and a heterozygous missense variant c.1301C>T (p.Ala434Val) in exon 13, which were inherited respectively from their parents. The oldest boy is a carrier with a novel missense variant c.1381G>C (p.Ala461Pro) in exon 13 which were inherited from his father. In the second family, c.1535G>A homozygous mutations were identified in the baby girl, which were inherited respectively from their parents. In silico analysis, several different types of bioinformatic software were utilized, which predicted that the novel variant c.1381G>C in PCCB gene was damaged. According to ACMG principle, the missense variant c.1381G>C (p.Ala461Pro) in exon 13 was a Variant of Undetermined Significance (VUS).One novel missense variant and two missense variants in PCCB gene were identified in the study. The novel variant of PCCB gene identified VUS was identified for the first time in the Chinese population, which enriched the mutational spectrum of PCCB gene.


Asunto(s)
Ligasas de Carbono-Carbono/genética , Metilmalonil-CoA Descarboxilasa/genética , Acidemia Propiónica/genética , Grupo de Ascendencia Continental Asiática/genética , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Heterocigoto , Humanos , Lactante , Recién Nacido , Mutación Missense , Tamizaje Neonatal , Linaje , Acidemia Propiónica/sangre , Acidemia Propiónica/diagnóstico , Espectrometría de Masas en Tándem
12.
Gene ; 784: 145593, 2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-33766710

RESUMEN

BACKGROUND: Obesity and metabolic syndrome frequently co-exist and define obese individuals into different obesity phenotypes, such as metabolically healthy obese (MHO), metabolically unhealthy obese (MUO) and metabolically unhealthy normal weight (MUNW). Growing evidence suggests that genetic predisposition and environmental factors can explain the heterogeneity among these phenotypes. METHODS: We conducted a case-control study including 130 MHO, 251 MUNW, 208 MUO and 336 health controls by genotyping 2 SNPs (rs2241766, rs1501299) in ADIPOQ to investigate possible associations between SNPs in the ADIPOQ gene with susceptibility to three obese phenotypes respectively in Chinese Han population. Unconditional logistic regressions were used to detect the association between ADIPOQ SNPs and MHO/MUNW/MUO risks. RESULTS: Variant G allele of rs2241766 was associated with a reduced odds of MUO (additive model: Adjusted OR = 0.55; 95% CI = 0.40-0.75; P < 0.001) and no evidence of any significant association between rs2241766 and MHO phenotype (additive model: Adjusted OR = 0.84; 95% CI = 0.61-1.16; P = 0.306) or MUNW phenotype (additive model: Adjusted OR = 0.95; 95% CI = 0.73-1.24; P = 0.720) was found. Minor allele T of rs1501299 were significantly associated with decreased risk of MHO (Adjusted OR = 0.53; 95% CI = 0.37-0.76; P < 0.001) and MUNW (Adjusted OR = 0.63; 95% CI = 0.48-0.83; P = 0.001) in additive genetic model after correction for multiple testing. CONCLUSIONS: The variant G allele of rs2241766 was negatively associated with risk of MUO and variant T allele of rs1501299 exhibited reduced odds for MHO and MUNW. Beyond that, future studies are warranted to validate and extend our findings.


Asunto(s)
Adiponectina/genética , Grupo de Ascendencia Continental Asiática/genética , Síndrome Metabólico/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , China/etnología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenotipo
13.
Gene ; 783: 145571, 2021 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-33737126

RESUMEN

Wilms tumor is a common pediatric tumor with abundant genetic drivers. YTHDC1 is an important reader of the N6-methyladenosine modification that widely regulates eukaryotic transcripts. YTHDC1 has been associated with the occurrence and development of some tumors. However, this is the first study on YTHDC1 gene polymorphisms and Wilms tumor susceptibility. In brief, we conducted a five-center case-control study to explore the associations between YTHDC1 polymorphisms (rs2293596 T > C, rs2293595 T > C, and rs3813832 T > C) and Wilms tumor susceptibility in Chinese children. A total of 404 cases and 1198 controls were successfully genotyped using TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as the evaluation indicators. We found that children with the 2-3 risk genotypes were more likely to develop Wilms tumor than those with the 0-1 risk genotypes (adjusted OR = 1.28, 95% CI = 1.01-1.62, P = 0.042). However, no other statistically significant results were found in this research study. The combined effect of YTHDC1 polymorphisms significantly increases Wilms tumor susceptibility. Our results need to be verified in different populations after increasing the sample size and controlling for confounding factors.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Proteínas del Tejido Nervioso/genética , Factores de Empalme de ARN/genética , Tumor de Wilms/genética , Estudios de Casos y Controles , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Masculino , Polimorfismo Genético
14.
Medicine (Baltimore) ; 100(13): e25258, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787609

RESUMEN

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.


Asunto(s)
Proteínas de Transporte de Catión/deficiencia , Hemocromatosis/genética , Hemocromatosis/terapia , Quelantes del Hierro/uso terapéutico , Mutación/genética , Anciano , Grupo de Ascendencia Continental Asiática/genética , Proteínas de Transporte de Catión/genética , Humanos , Masculino , Persona de Mediana Edad
15.
Medicine (Baltimore) ; 100(12): e23716, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761627

RESUMEN

ABSTRACT: Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51-0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08-0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48-0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09-0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.


Asunto(s)
Neoplasias Pulmonares/epidemiología , ARN Largo no Codificante/genética , Anciano , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , Femenino , Técnicas de Genotipaje , Humanos , Neoplasias Pulmonares/genética , Masculino , MicroARNs/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores Protectores
16.
Medicine (Baltimore) ; 100(12): e24843, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761643

RESUMEN

ABSTRACT: Study has demonstrated that TNIP1 polymorphisms are associated with an increased risk of HBV-induced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the correlation between polymorphisms in TNIP1 and HCC risk in a Northwest Chinese Han population.A case-control study was conducted including 473 Hepatocellular carcinoma patients and 564 healthy controls. Three SNPs (rs3792792, rs7708392, and rs10036748) were genotyped with Sequenom MassARRAY technology and their associations with HCC risk were analyzed. These data were evaluated using the Chi-square test/Fisher's exact test, genetic model analysis, and haplotype analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association.Patients with the "G" allele of TNIP1 rs7708392 showed a significantly increased risk of HCC (OR = 1.24, 95%CI: 1.01-1.52, P = .042). Significant association was also shown between TNIP1 rs7708392 and HCC susceptibility in Additive model (OR = 1.25; 95% CI = 1.01-1.54; P = .040). Besides, we also found that the "GC" haplotype of rs7708392 and rs10036748 was significantly associated with higher occurrence of HCC (OR = 1.25, 95% CI: 1.01-1.54, P = .039).These results demonstrate that TNIP1 polymorphisms are associated with increased HCC risk in a Northwest Chinese Han population for the first time, which warrants further investigation in the future.


Asunto(s)
Carcinoma Hepatocelular/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Neoplasias Hepáticas/genética , Grupo de Ascendencia Continental Asiática/genética , Carcinoma Hepatocelular/epidemiología , Estudios de Casos y Controles , China/epidemiología , Femenino , Técnicas de Genotipaje , Haplotipos , Humanos , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Modelos Genéticos , Polimorfismo de Nucleótido Simple
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 232-237, 2021 Mar 10.
Artículo en Chino | MEDLINE | ID: mdl-33751531

RESUMEN

OBJECTIVE: To explore the clinical characteristics and genetic basis for a pair of twins affected with hyaline fibromatosis syndrome (HFS). METHODS: Clinical data of the twins were retrospectively analyzed. High-throughput sequencing was carried out to detect potential pathogenic variants. CLUSTALX was employed to analyze cross-species conservation of the mutant amino acids. Impact of the mutations was predicted by using software including PolyPhen-2 and Mutation taster. RESULTS: The pair of twins have featured growth and intelligence retardation, and were found to carry compound heterozygous variants of the ANTXR2 gene including c.1214G>A and c.1074delT, among which c.1214G>A was unreported previously. Both variants were predicted to be pathogenic. In addition to growth and mental delay, the pair of twins also featured hyperplasia of the gum and soft tissue-like masses of the auricle. The younger brother had rupture of the auricle mass during follow-up. CONCLUSION: The patients' condition can probably be attributed to the compound heterozygous variants of the ANTXR2 gene. Above finding has facilitated molecular diagnosis of the patients.


Asunto(s)
Hialinosis Sistémica , Receptores de Péptidos , Grupo de Ascendencia Continental Asiática/genética , China , Humanos , Hialinosis Sistémica/genética , Masculino , Mutación , Linaje , Receptores de Péptidos/genética , Estudios Retrospectivos
18.
Medicine (Baltimore) ; 100(12): e25160, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761690

RESUMEN

RATIONALE: Hereditary Protein C (PC) deficiency is a rare genetic disorder caused by PROC gene mutation. In this article, we report a case of PC deficiency in a Chinese family due to a novel PROC gene mutation. STUDY SUBJECT: The proband presented with recurrent cerebral infarction over the course of the previous 3 years. He was admitted to the hospital due to signs of mental retardation. DIAGNOSES: Physical examination, laboratory tests, and magnetic resonance imaging demonstrated that the proband had a manifestation of PC deficiency that included acute cerebral infarction. DNA sequencing analysis revealed a missense variant, c.1015G > A (p.V339 M from valine to methionine) in exon 9 of the PROC gene. In addition, Sanger sequencing confirmed that the proband's son was heterozygous for the same variant. Therefore, the PROC gene mutation was transmitted in an autosomal dominant inheritance manner. INTERVENTIONS: The patient was treated with a daily dosage of Warfarin (3.5 mg) and was scheduled to undergo regular blood coagulation tests. OUTCOMES: At the 3-month follow-up appointment, the patient showed improvements in his overall health condition. LESSONS: We identified a novel missense mutation in the PROC gene in a Chinese family which caused a decrease in the PC antigen level and recurrent cerebral infarction.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Deficiencia de Proteína C/genética , Proteína C/genética , Anticoagulantes/uso terapéutico , Angiografía Cerebral , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/genética , Infarto Cerebral/prevención & control , Imagen de Difusión por Resonancia Magnética , Genes Dominantes , Humanos , Trombosis Intracraneal/genética , Trombosis Intracraneal/prevención & control , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Deficiencia de Proteína C/complicaciones , Recurrencia , Warfarina/uso terapéutico
19.
Medicine (Baltimore) ; 100(12): e25171, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761695

RESUMEN

RATIONALE: Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection. It has an aggressive clinical course; however, it usually does not recur after recovery in cases of spontaneous ANE. Nevertheless, there are several studies reporting recurrences in familial ANE with RAN-binding protein 2 (RANBP2) mutation. There are few cases of familial ANE with RANBP2 mutation in Asian populations. PATIENTS CONCERNS: A 21-month-old Korean boy who was previously healthy, presented with seizure following parainfluenza - a virus and bocavirus infection, followed by 2 recurrent seizure episodes and encephalitis after febrile respiratory illnesses. Meanwhile, his 3-year-old sister had focal brain lesions on neuroimaging studies when evaluated for head trauma. The siblings also had an older brother who presented status epilepticus after febrile respiratory illness at the age of 10 months old. DIAGNOSIS: Brain magnetic resonance imaging was performed to evaluate the seizure and neurologic symptoms. Imaging findings showed variable spectrum - from non-specific diffuse white matter injury pattern to typical "tricolor pattern" of the ANE on diffusion-weighted images. The other 2 siblings showed focal lesions in both external capsules and severe diffuse brain edema. Genetic tests identified a heterozygous missense mutation in the RANBP2 [c.1754C>T (p.Thr585Met)] in 2 siblings and their mother. INTERVENTIONS: Patients were treated conservatively with anticonvulsive agents, intravascular immunoglobulin, and steroids. OUTCOMES: Among the 3 siblings, 2 male siblings died from familial ANE, whereas the female sibling was asymptomatic. LESSONS: These cases highlight the radiological aspects of familial ANE with incomplete penetrance of the RANBP2 gene in 3 family members, showing variable involvements of the brain and natural history on magnetic resonance images. Radiologists should be aware of the typical and atypical imaging findings of familial ANE for prompt management of affected patients.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Leucoencefalitis Hemorrágica Aguda/diagnóstico por imagen , Leucoencefalitis Hemorrágica Aguda/genética , Chaperonas Moleculares/genética , Mutación Missense , Proteínas de Complejo Poro Nuclear/genética , Corticoesteroides/uso terapéutico , Anticonvulsivantes/uso terapéutico , Preescolar , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Leucoencefalitis Hemorrágica Aguda/complicaciones , Leucoencefalitis Hemorrágica Aguda/tratamiento farmacológico , Masculino , Penetrancia , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Sustancia Blanca/diagnóstico por imagen , Adulto Joven
20.
Medicine (Baltimore) ; 100(11): e24818, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725949

RESUMEN

ABSTRACT: Osteosarcoma is a malignant tumor that develops from a mesenchymal cell line and is caused by gene-environment interactions. This study aimed to explore whether TIMP2/TIMP3 polymorphisms influenced the osteosarcoma risk.The expression of the TIMP2 and TIMP3 genes in osteosarcoma histiocytes was analyzed by immunohistochemistry. In this case-control study, which includes samples from 499 patients and 500 healthy controls, 10 single-nucleotide polymorphisms (SNPs) in TIMP2 and TIMP3 were selected. Furthermore, we used the Agena MassARRAY platform for genotyping. The statistical analysis was performed using χ2 test/Fisher exact test, and logistic regression analysis.The immunohistochemistry results showed that the expression of TIMP2 is obvious higher in osteosarcoma histiocytes than in the normal histiocytes. The association study indicated that the allele of rs2277698 and rs4789936 were protective SNPs reducing the risk of osteosarcoma (odds ratios  > 1, P < .05) by the χ2 test. In the genetic model, logistic regression analyses revealed that the rs2277698 and rs4789936 were associated with decreasing the risk of osteosarcoma under the codominant model, dominant model, and log-additive model. Stratification analysis revealed that 2 SNPs (rs2277698 and rs4789936) were significantly associated with a reduced risk of osteosarcoma in allele and genetic model after stratification by gender or age (P < .05). In addition, the haplotype "Trs2277698Crs2009169Crs7342880" of TIMP2 was associated with decreasing the osteosarcoma risk. The "Ars9609634Trs11547635" of TIMP3 was associated with reducing the osteosarcoma risk.This finding shed new light on the high expression of TIMP2 polymorphisms may contribute to decreasing the osteosarcoma risk in Zhejiang populations.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Neoplasias Óseas/genética , Osteosarcoma/genética , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-3/genética , Adolescente , Anciano , Alelos , Neoplasias Óseas/etnología , Estudios de Casos y Controles , China/etnología , Femenino , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Humanos , Inmunohistoquímica , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Osteosarcoma/etnología , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Adulto Joven
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