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OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Treacher-Collins syndrome (TCS) through whole exome sequencing (WES). METHODS: A TCS pedigree which was diagnosed at the Women and Children's Hospital Affiliated to Qingdao University on February 5, 2020 was selected as the study subject. Following collection of clinical data, WES was carried out. Candidate variant was validated through Sanger sequencing and bioinformatic analysis. RESULTS: The WES results showed that the proband has harbored a heterozygous c.3337C>T variant of the TCOF1 gene, and Sanger sequencing confirmed that his mother and brother also carried the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.3337C>T variant of the TCOF1 gene probably underlay the pathogenesis of TCS in this pedigree.
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Pueblo Asiatico , Disostosis Mandibulofacial , Niño , Femenino , Humanos , Masculino , Pueblo Asiatico/genética , China , Secuenciación del Exoma , Disostosis Mandibulofacial/genética , Madres , Proteínas Nucleares/genética , Linaje , Fosfoproteínas/genéticaRESUMEN
BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer morbidity and mortality in men worldwide; however, PCa incidence and mortality rates vary widely across geographic regions and ethnic groups. The current study was designed to elucidate the pivotal factors involved in PCa occurrence and development. METHODS: We performed RNA sequencing on the prostate tumor and adjacent normal tissues from Chinese PCa patients. Genes identified via genome-wide expression profile analysis were validated by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Hypermethylation of CpG islands was assessed by nested methylation-specific PCR. Whole genome microarray analysis was performed using an Affymetrix GeneChip. RESULTS: We identified nine possible abnormally expressed genes (P < .05) and then revealed TWIST2 as having strikingly lower expression in tumors than in control tissues (P < .01). Low messenger RNA expression levels of TWIST2 were associated with hypermethylation of CpG islands in its promoter region. In accordance with these findings, PCa tumor tissues showed markedly decreased TWIST2 protein expression compared to that in both normal and prostatic intraepithelial neoplasia tissues by immunohistochemical staining. Ectopic expression of TWIST2 in LNCap cells not only inhibited cell proliferation and colony formation in vitro and tumor growth in vivo but also induced transcriptional repression of a cell proliferation-related gene cohort, including androgen receptor signaling mediators, cyclins, homeobox genes, forkhead box genes, and SOX2. CONCLUSIONS: Our results suggest that TWIST2 could function as a tumor suppressor involved in the pathogenesis of PCa by influencing the expression of target genes and that hypermethylation of the TWIST2 promoter in prostate tumors may be an underlying mechanism for TWIST2 transcriptional silencing.
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Neoplasias de la Próstata/genética , Proteínas Supresoras de Tumor , Proteína Relacionada con Twist 2/genética , China , Islas de CpG , Metilación de ADN , Epigénesis Genética , Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Análisis por Micromatrices , Regiones Promotoras Genéticas , Neoplasia Intraepitelial Prostática/química , Neoplasias de la Próstata/química , ARN Mensajero/análisis , Análisis de Secuencia de ARN , Células Tumorales Cultivadas , Proteína Relacionada con Twist 2/análisis , Proteína Relacionada con Twist 2/fisiologíaRESUMEN
BACKGROUND: The tumor suppressor forkhead box P4 (FOXP4) plays important roles in oncogenesis, and the FOXP4 variant rs1983891 is associated with prostate cancer (PCa) in several studies. However, association studies conducted in Northern and Southern Chinese have provided conflicting results. Therefore, here we performed fine mapping of FOXP4 to identify the association with PCa and the potential application in Chinese men. METHODS: We examined 11 variants spaced approximately 55 kb apart spanning FOXP4 using high-resolution melting-curve analysis and sequencing methods in 286 PCa patients and 630 controls, and the association between these variants and PCa risk was evaluated. Additionally, we evaluated the cumulative effect of rs4714476 and 2 variants in 8q24 (rs16901966, rs10090154) confirmed in our previous study. RESULTS: Of 11 SNPs, only rs4714476-C at the 5' near gene of FOXP4 was associated with increased age-adjusted PCa risk (p = 0.012, OR = 1.32, 95% CI = 1.06 - 1.63) and aggressive PCa (p = 0.026). The CG haplotype covering rs4714476-C demonstrated significant differences between PCa cases and controls (p = 0.009). The cumulative effect analysis showed men who carried any combination of 1, 2, or 3 risk genotypes had a gradually increased PCa risk (age-adjusted OR is from 1.244 to 3.312). CONCLUSIONS: These data suggest that rs4714476 at the 5' near gene of FOXP4 potentially contributes to the susceptibility of PCa in Chinese men. The cumulative effect of rs4714476 at FOXP4 and 8q24 could increase PCa risk.
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Factores de Transcripción Forkhead/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Estudios de Casos y Controles , China , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/etnología , Factores de Riesgo , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: To identify the genetic risk of six genetic variants at 8q21 and 8q24 (including rs1512268, A; rs12543663, C; rs10086908, C; rs1016343, T; rs13252298, A, and rs6983561, C) associated with prostate cancer in Beijing and Tianjin (Jing-jin) area residents in northern China. METHODS: 574 subjects were enrolled. Blood samples and clinical information were collected from histologically confirmed prostate cancer cases (n = 286) and clinically evaluated matched normal controls (n = 288) from Chinese men in northern China. Six SNPs at 8q21 and 8q24 were genotyped by high-resolution melt and sequencing in subjects. We compared statistical differences between the prevalence of risk genotypes with prostate cancer in cases and controls and analyzed the association between clinical covariates and risk loci in case groups to infer their relationship with aggressive prostate cancer. RESULTS: Three genotypes of rs10086908, CC (OR = 2.48; 95% CI = 1.02 - 5.98, p = 0.037) rs1016343, TT (OR = 1.64, 95% CI = 1.07 - 2.53, p = 0.023); and rs6983561, CC (OR = 1.91; 95% CI = 1.09 - 3.63, p = 0.044) at 8q24 were identified to be associated with prostate cancer risk in Jing-jin Chinese. The D' values of both two-locus haplotypes (T-A: rs1016343 vs. rs13252298; T-C: rs1016343 vs. rs6983561) were 0.907 and 0.859, respectively, the three-locus haplotype, only TAC constituted by the loci (rs1016343, T; rs13252298, A; rs6983561, C) was also associated with prostate cancer (p = 0.033), revealing rs1016343 vs. rs6983561 with significant differences between cases and controls. According to clinical covariates and odds ratios of risk genotypes relative to non-risk genotypes, rs6983561, CC was associated with age (OR = 2.5; 95% CI = 1.02 - 6.13, p = 0.039), and tumor aggressiveness (OR = 1.15; 95% Cl = 1.06 - 1.23, p = 0.013). CONCLUSIONS: The loci including rs10086908, rs1016343, and rs6983561 at 8q24 could be associated with prostate cancer in Jing-jin residents in northern China. Our results suggest that these loci could influence susceptibility to prostate cancer in the northern Chinese population.
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Cromosomas Humanos Par 8 , Proteínas de Homeodominio/genética , Neoplasias de la Próstata/genética , Factores de Transcripción/genética , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Bone development involves the rapid proliferation and differentiation of osteogenic lineage cells, which makes accurate chromosomal segregation crucial for ensuring cell proliferation and maintaining chromosomal stability. However, the mechanism underlying the maintenance of chromosome stability during the rapid proliferation and differentiation of Prx1-expressing limb bud mesenchymal cells into osteoblastic precursor cells remains unexplored. METHODS: A transgenic mouse model of RanGAP1 knockout of limb and head mesenchymal progenitor cells was constructed to explore the impact of RanGAP1 deletion on bone development by histomorphology and immunostaining. Subsequently, G-banding karyotyping analysis and immunofluorescence staining were used to examine the effects of RanGAP1 deficiency on chromosome instability. Finally, the effects of RanGAP1 deficiency on chromothripsis and bone development signaling pathways were elucidated by whole-genome sequencing, RNA-sequencing, and qPCR. RESULTS: The ablation of RanGAP1 in limb and head mesenchymal progenitor cells expressing Prx1 in mice resulted in embryonic lethality, severe cartilage and bone dysplasia, and complete loss of cranial vault formation. Moreover, RanGAP1 loss inhibited chondrogenic or osteogenic differentiation of mesenchymal stem cells (MSCs). Most importantly, we found that RanGAP1 loss in limb bud mesenchymal cells triggered missegregation of chromosomes, resulting in chromothripsis of chromosomes 1q and 14q, further inhibiting the expression of key genes involved in multiple bone development signaling pathways such as WNT, Hedgehog, TGF-ß/BMP, and PI3K/AKT in the chromothripsis regions, ultimately disrupting skeletal development. CONCLUSIONS: Our results establish RanGAP1 as a critical regulator of bone development, as it supports this process by preserving chromosome stability in Prx1-expressing limb bud mesenchymal cells.
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Diferenciación Celular , Inestabilidad Cromosómica , Esbozos de los Miembros , Células Madre Mesenquimatosas , Animales , Ratones , Desarrollo Óseo , Condrogénesis/genética , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genética , Esbozos de los Miembros/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratones Noqueados , Osteogénesis/genética , Transducción de SeñalRESUMEN
OBJECTIVE: To explore the association between the common variations of TET2 (rs7679673, A), MTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes and prostate cancer (Pca) risk in Chinese population in Beijing, and to understand the relationship between genotypes and phenotypes including clinical characteristics and life style, etc. in patients with prostate cancer. METHODS: Based on a case-control study, 124 patients with prostate cancer and 138 age-matched control subjects were recruited. Information of clinical phenotype and life style, etc. in the prostate cancer patients was collected. We compared the differences of allele and genotype frequencies of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) gene expressions between the two groups for the allele and genotype frequencies, and explored the relationship between different genotypes and clinical features such as patient age, BMI, Gleason score, PSA level and tumor stage, by Chi-square test in patients with PCa. Multifactor dimensionality reduction was used to detect the gene-gene interactions. RESULTS: The FAM84B (rs12543663, C) C carriers frequency had significant difference between the case group and the control group (χ(2) = 3.980 P = 0.046; OR = 1.883; 95%CI = 1.006-3.526). The allele and genotype frequencies of TET2 gene (rs7679673, A) and LMTK2 gene (rs6465657, T) were not significantly different between the case group and the control group (P > 0.05). Analysis of the genotypes and clinical phenotypes showed that the genetic type of FAM84B C carriers [CX (CC + CA)] were significantly associated with cancer stage (χ(2) = 9.585; P = 0.002; OR = 3.740; 95%CI = 1.580 - 8.853). Association between three loci and 12 kind of relevant outcomes was found in TET2 A carriers and the smoking and drinking patients (all P < 0.05). Significant correlation was also found between LMTK2 (rs6465657, T) TX carriers and surgery (χ(2) = 8.612; P = 0.003; OR = 0.174; 95%CI 0.049 - 0.620). No significant correlation was seen with other covariates (P > 0.05). Dendrogram analysis among the three loci showed that the best model consisted of the three sites (P = 0.0270), cross validation consistency: 10/10, and testing balanced accuracy: 0.5120. There may be gene-gene interaction among TET2 (rs7679673, A), LMTK2 (rs6465657, T), and FAM84B (rs12543663, C). CONCLUSIONS: There may be obvious association of FAM84B (rs12543663, C) gene with prostate cancer risk and the stages, and the synergistic effects of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes may have an association with prostate cancer risk in Chinese population.
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Proteínas de Unión al ADN/genética , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias de la Próstata/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Proteínas de Unión al ADN/metabolismo , Dioxigenasas , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Fenotipo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Factores de Riesgo , FumarRESUMEN
Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate.
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Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Animales Modificados Genéticamente , Factores de Transcripción Forkhead/genética , Células 3T3 NIH , Oncogenes , Próstata , Neoplasias de la Próstata/genéticaRESUMEN
OBJECTIVE: To investigate the association of prostate cancer (PCa) with PDLIM5 (rs17021918, T), SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) in Chinese men. METHODS: We included 124 PCa patients and 138 normal controls in this study, compared the alleles and genotypes of PDLIM5 (rs17021918, T) , SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) of the two groups, and explored the association of each of the genes with the age, body mass index (BMI), Gleason score, PSA level and tumor stage of the patients. We analyzed the gene-gene interaction using the multifactor dimensionality reduction method (MDR). RESULTS: There were no statistically significant differences in the frequency distribution of the risk alleles and genotypes of PDLIM5, SLC22A3 and NKX3-1 between the case and control groups (P > 0.05), nor were the three gene loci significantly associated with the age, Gleason score, PSA level and pathological grade of the PCa patients (CP < 0.05). MDR analysis showed no interaction between PDLIM5 and NKX3-1, but tree-diagram analysis revealed a possible synergistic action of the two polymorphism loci. CONCLUSION: PCa might not be associated with PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) in Chinese men. However, PDLIM5 and NKX3-1 might have a synergistic action on the risk PCa.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Homeodominio/genética , Proteínas con Dominio LIM/genética , Proteínas de Transporte de Catión Orgánico/genética , Neoplasias de la Próstata/genética , Factores de Transcripción/genética , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Background: The association between paracentral acute middle maculopathy (PAMM) and visual acuity in patients with retinal artery occlusion (RAO) is unknown. This study explored the clinical features and prognostic factors for visual acuity of RAO accompanied by PAMM. Methods: This retrospective study included patients with RAO who underwent FFA and OCT examinations at Shenzhen Eye Hospital from July 2015 to June 2019. The changes in vision and macular structure were observed. Results: Eighty-eight patients were included. There were 58 patients (65.9%) with central RAO (CRAO) and 30 (34.1%) with branch RAO (BRAO). Fifty-two eyes were diagnosed with PAMM, of which 33 eyes (63.5%) were from CRAO patients and 19 (36.5%) were from BRAO patients. At diagnosis, the PAMM group had significantly better logMAR BCVA values than the no-PAMM group (median (IQR), 1.35 (0.725-2) vs. 2.15 (1.47-2.3), P=0.002). In addition, the PAMM group had significantly better logMAR BCVA values during follow-up than the no-PAMM group (median (IQR), 1 (0.05-2) vs. 2 (1.15-2.3), P=0.001). After adjustment for age, gender, CRAO/BRAO, comorbidities, and symptom duration, PAMM was associated with good visual acuity improvement (RR = 3.29, 95% CI: 1.29-8.37, P=0.013). Conclusion: PAMM was associated with good visual acuity improvement during follow-up in patients with RAO.
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OBJECTIVE: This study aimed to explore the application effect of clinical nursing pathway model in elderly patients with hypertension and cerebral infarction. METHODS: A total of 106 elderly patients with hypertension and cerebral infarction were recruited and divided into a control group (n=51) and a test group (n=55). Both groups of patients received conventional care, and the test group was given additional care if clinical nursing pathway. The blood pressure indexes, knowledge of stroke, nursing satisfaction, neurological deficit, and activity of daily living (ADL) of the two groups of patients were observed. RESULTS: After nursing care, the scores of Stroke Knowledge Questionnaire (SKQ) and Barthel index (BI) increased in both groups, and they were significantly higher in the test group than in the control group. The scores of systolic blood pressure (SBP), diastolic blood pressure (DBP) and National Institutes of Health Stroke Scale (NIHSS) decreased significantly in both groups after nursing, and they were lower in the test group than the control group. In addition, patients in the test group exhibited higher nursing satisfaction than the control group, as well as higher rates of blood pressure control at discharge, two months, four months and six months after discharge. CONCLUSION: The application of clinical nursing pathway can improve the disease cognition and quality of life of elderly patients with hypertension and cerebral infarction, and promote their recovery.
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BACKGROUND: Breast cancer patients with metabolic syndrome have an increased risk of cardiovascular disease. These patients are more prone to suffer from cardiotoxicity after anticancer therapy. Patients after completion of cancer-related comprehensive therapy, who show normal myocardial function, may already have subclinical myocardial dysfunction. We sought to evaluate the subclinical myocardial dysfunction in breast cancer patients with metabolic syndrome after cancer-related comprehensive therapy. Methods. In this study, 45 breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy, 45 non-breast cancer patients with metabolic syndrome, and 30 breast cancer patients without metabolic syndrome after therapy were enrolled. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured using echocardiogram. RESULTS: All the patients had normal LVEF. However, nine breast cancer patients with metabolic syndrome (20%) had GLS that was lower than -17%, while all the noncancer patients had normal GLS. Breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF, compared with noncancer patients with metabolic syndrome. Furthermore, we found that decrease of age was associated with reduction of LVEF and that use of trastuzumab for 1 year was a significant factor associated with reduction of GLS. In addition, breast cancer patients with metabolic syndrome had a decrease of GLS, compared with breast cancer patients without metabolic syndrome after cancer-related therapy. CONCLUSIONS: Breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy suffered from subclinical myocardial dysfunction. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer-related comprehensive therapy.
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Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts. Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF. Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF.
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Astroviral infection is considered to be one of the causes of mammalian diarrheal diseases. It has been shown that astrovirus infections cause varying degrees of diarrhea in turkeys and mice. However, the pathogenesis of porcine astrovirus is unknown. In this study, the virulence of a cytopathic porcine astrovirus (PAstV) strain (PAstV1-GX1) isolated from the PK-15 cell line was tested using seven-day-old nursing piglets. The results showed that PAstV1-GX1 infection could cause mild diarrhea, growth retardation, and damage of the villi of the small intestinal mucosa. However, all the above symptoms could be restored within 7 to 10days post inoculation (dpi). To evaluate the innate immunity response of PAstV in vivo, the alteration of inflammatory cytokine expression in piglets infected with PAstV1-GX1 was determined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The mRNA expression levels of the IFNß and ISG54 were found to be significantly elevated in virus-infected piglets. In contrast, expression of IFNλ was downregulated in piglets infected with PAstV1-GX1. In addition, the mRNA expression of the tight junction protein 1 and 2 and zonula occludin 1, which are associated with the intestinal barrier permeability, were affected after PAstV1 infection. The present study adds to our understanding of the pathogenic mechanism of PAstV and has established an animal model for further study of pig astrovirus infection.
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Infecciones por Astroviridae/veterinaria , Astroviridae/fisiología , Enfermedades de los Porcinos/virología , Animales , Astroviridae/aislamiento & purificación , Astroviridae/patogenicidad , Biopsia , Citocinas/metabolismo , Diarrea/veterinaria , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Especificidad de Órganos , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/metabolismo , Enfermedades de los Porcinos/patología , Carga Viral , Esparcimiento de VirusRESUMEN
BACKGROUND: Deletions in Xq21 cause various congenital defects in males including choroideremia, deafness and mental retardation, depending on their size and gene content. Until now only a limited number of patients with Xq21 deletions has been reported. CASE PRESENTATION: Here we describe a 17-year-old male with choroideremia, deafness, and mental retardation syndrome. Using SNP arrays, an 8.05 Mb deletion in Xq21 was identified inherited from the apparently healthy mother. The deleted region harbors 12 OMIM genes, of which POU3F4, CHM, and ZNF711 might have contributed to the patient's phenotype including hearing loss, poor vision, and intellectual disability. Moreover, the patient's mother exhibits a normal phenotype while carrying the same deletion, which is often observed in previous studies on female carriers in families with this syndrome. CONCLUSIONS: Our study confirms the causative effect between the Xq21 deletion in males and choroideremia, deafness and mental retardation.
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Healthy longevity has been an unremitting pursuit of human, but its genetic and the environment causes are still unclear. As longevity population is a good healthy aging model for understanding how the body begin aging and the process of aging, and plasma lipids metabolism and balance is a very important to life maintain and physiologic functional turnover. It is important to explore how the effect of genetic variants associated long-life individuals on lipids metabolism and balance. Therefore, we developed a comparative study based population which contains 2816 longevity and 2819 control. Through whole-exome sequencing and sanger sequencing genotypes, we identified four new single nucleotide polymorphisms of HLA-DQB1(major histocompatibility complex, class II, DQ beta 1), rs41542812 rs1049107 rs1049100 rs3891176(Prange=0.048-2.811×10-8 for allele frequencies), associated with longevity in Chinese Longevity Cohort. Further, by analysis of the longevity-variants linked to blood lipids, we identified HLA-DQB1 rs1049107, T-carriers (PHDL=0.006, OR: 11.277; PTG=9.095×10-7, OR: 0.025; PLDL/HDL=0.047, OR: 1.901) and HLA-DQB1 rs1049100, T-carriers (PTG=1.799×10-6, OR: 0.028) associated with lipid homeostasis in long lived individuals. Our finding showed that longevity and lipid homeostasis were associated with HLA-DQB1 and suggested that immune gene variants could act on both new function of maintaining the homeostasis and anti-aging in longevity.
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Cadenas beta de HLA-DQ/genética , Metabolismo de los Lípidos/genética , Longevidad/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano de 80 o más Años , Pueblo Asiatico/genética , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , China , Biología Computacional , Estudios Transversales , Bases de Datos Genéticas , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Haplotipos , Estado de Salud , Homeostasis , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Oportunidad Relativa , FenotipoRESUMEN
Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79-4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.
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Consumo de Bebidas Alcohólicas/efectos adversos , Pueblo Asiatico/genética , Salud del Hombre , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Adulto , Anciano , Alelos , Índice de Masa Corporal , Estudios de Casos y Controles , China/epidemiología , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Neoplasias de la Próstata/epidemiología , Riesgo , Fumar/efectos adversos , Encuestas y CuestionariosRESUMEN
The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects is limited; in addition, the majority of oldest-old subjects are females. Evidence has accumulated that multiple genetic factors play important roles in determining susceptibility to dyslipidemia and extended life span. Cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible candidate genes for human longevity owing to their functionally related modulation of circulating lipid homeostasis; however, few studies have considered their interplay. In this study, we analyzed the distribution of CETP*V (rs5882) and APOE*4 (rs429358 and rs7412) in 372 oldest-old Chinese women (aged 80-109) and 340 controls (aged 20-58). In addition to replicating the association of longevity, our main goal was to evaluate the contribution of CETP*V, APOE*4 and CETP*APOE interaction to the risk of dyslipidemia. Only APOE*4 conferred a risk against longevity and was associated with high-cholesterol (hTC) and mixed dyslipidemia for oldest-old females. Moreover, CETP*V was found to be associated with hypertriglyceridemia (hTG) independently from APOE*4, age, BMI, alcohol drinking, TC, TG, HDL-c, and LDL-c. The stratification test, multivariable-adjusted logistic regression, and nonparametric MDR analysis all suggested a significant CETP*APOE interaction associated with hTG. The unadjusted odds for hTG were more than 4-fold in subjects with CETP*V and APOE*4 than those without either (OR=4.36, P<0.001). These results provide evidence of strong independent associations between hTG and CETP*V in oldest-old Chinese females, and APOE*4, as an independently non-significant variant, might interact with CETP*V resulting in an increased risk for hTG.
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Apolipoproteínas E/genética , Proteínas de Transferencia de Ésteres de Colesterol/genética , Hipertrigliceridemia/genética , Longevidad/genética , Polimorfismo Genético , Adulto , Anciano de 80 o más Años , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipertrigliceridemia/sangre , Lípidos/sangre , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: The single nucleotide polymorphism (SNP) rs1465618 in THADA at 2p21 has been identified as being associated with prostate cancer (PCa) risk in Europeans; however, it is not clear whether the SNP is related to PCa risk in multiple populations. We investigated the association of rs1465618 in THADA with PCa in a Chinese population and carried out a meta-analysis in multiple populations, testing the relevance of this SNP for PCa risk. PATIENTS AND METHODS: We genotyped the SNP using high resolution melting (HRM) analysis and assessed its association with PCa risk in a case-control study of 289 PCa patients and 288 controls in a Chinese population. A meta-analysis was carried out with 36,313 PCa patients and 36,485 controls to evaluate the association of rs1465618 with PCa risk in multiple populations. RESULTS: rs1465618 in THADA was significantly associated with PCa risk (p = 0.026; odds ratio (OR) 1.327, 95% confidence interval (CI) 1.035-1.700). Furthermore, the rs1465618 variant genotype was associated with PCa aggressiveness (p = 0.044; OR = 2.053, 95% CI = 1.015-6.602) in the Chinese population. The meta-analysis showed that rs1465618 was significantly associated with PCa risk in multiple populations (p = 1.0×10(-8); OR = 1.127, 95% CI = 1.085-1.171). CONCLUSION: Our results showed that rs1465618 in THADA may be a shared susceptibility variant for PCa in multiple populations. THADA gene polymorphisms may impact PCa susceptibility and progression.
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Biomarcadores de Tumor/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Anciano , China/epidemiología , Marcadores Genéticos/genética , Humanos , Masculino , Prevalencia , Neoplasias de la Próstata/diagnóstico , Medición de RiesgoRESUMEN
BACKGROUND: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. MATERIALS AND METHODS: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically- confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. RESULTS: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, P=7.3?10-5), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, Padj=1.1?10-4). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ≥65 years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype (P=4.6?10-5-3.0?10-2). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, P=1.0?10-5) across Asian, Caucasian and African American populations. CONCLUSIONS: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.
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Cromosomas Humanos Par 8/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético/genética , Neoplasias de la Próstata/genética , Estudios de Casos y Controles , Humanos , Masculino , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity. METHODS: We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and 515 controls), then performed a meta-analysis that integrated the current study and previously published ones. Pooled odds ratios (OR) were calculated for allele contrasts, dominant and recessive inheritance models to assess the association between CETP 405V and longevity according to the ethnic stratification. RESULTS: Our case-control data indicated that CETP 405V is a longevity risk allele in all genetic models (P additive =0.008; P dominant =0.008, OR(dominant)=0.673; P recessive =0.017, OR(recessive)=0.654) after adjustment for the apolipoprotein E (APOE) ε4 allele, body mass index and high-density lipoprotein cholesterol. A synergy was detected between 405V and APOE ε4 (P=0.001, OR=0.530). Eight studies were eligible for meta-analysis, which confirmed 405V is the risky allele against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74-0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80, 95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in East Asians but no significant association was found in Europeans or white Americans. CONCLUSION: Our case-control study suggests CETP 405V as a risk allele against longevity in Chinese. The meta-analysis suggests the involvement of CETP 405V is protective in Ashkenazi Jews but is a risk allele against longevity in the East Asian (Chinese) population.