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1.
Arch Gynecol Obstet ; 308(3): 787-795, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36602559

RESUMO

BACKGROUND: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China. METHODS: In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview. RESULTS: NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview. CONCLUSIONS: NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.


Assuntos
Síndrome de Down , Gestantes , Feminino , Gravidez , Humanos , Laboratórios Clínicos , Diagnóstico Pré-Natal/métodos , Síndrome de Down/diagnóstico , Aneuploidia , Resultado da Gravidez
2.
J Transl Med ; 20(1): 536, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401256

RESUMO

BACKGROUND: Chromosomal aneuploidy is the most common birth defect. However, the developmental mechanism and gene expression profile of fetuses with chromosomal aneuploidy are relatively unknown, and the maternal immune changes induced by fetal aneuploidy remain unclear. The inability to obtain the placenta multiple times in real-time is a bottleneck in research on aneuploid pregnancies. Plasma cell-free DNA (cfDNA) carries the gene expression profile information of its source cells and may be used to evaluate the development of fetuses with aneuploidy and the immune changes induced in the mother owing to fetal aneuploidy. METHODS: Here, we carried out whole-genome sequencing of the plasma cfDNA of 101 pregnant women carrying a fetus with trisomy (trisomy 21, n = 42; trisomy 18, n = 28; trisomy 13, n = 31) based on non-invasive prenatal testing (NIPT) screening and 140 normal pregnant women to identify differential genes according to the cfDNA nucleosome profile in the region around the transcription start sites (TSSs). RESULTS: The plasma cfDNA promoter profiles were found to differ between aneuploid and euploid pregnancies. A total of 158 genes with significant differences were identified, of which 43 genes were upregulated and 98 genes were downregulated. Functional enrichment and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases found that these signal pathways were mainly related to the coordination of developmental signals during embryonic development, the control of cell growth and development, regulation of neuronal survival, and immune regulation, such as the MAPK, Hippo, TGF-ß, and Rap1 signaling pathways, which play important roles in the development of embryonic tissues and organs. Furthermore, based on the results of differential gene analysis, a total of 14 immune-related genes with significant differences from the ImmPort database were collected and analyzed. These significantly different immune genes were mainly associated with the maintenance of embryonic homeostasis and normal development. CONCLUSIONS: These results suggest that the distribution characteristics of cfDNA nucleosomes in maternal plasma can be used to reflect the status of fetal development and changes of the immune responses in trisomic pregnancies. Overall, our findings may provide research ideas for non-invasive detection of the physiological and pathological states of other diseases.


Assuntos
Ácidos Nucleicos Livres , Nucleossomos , Humanos , Feminino , Gravidez , Nucleossomos/genética , Nucleossomos/metabolismo , Transcriptoma , Aneuploidia , Feto/metabolismo , Trissomia , Ácidos Nucleicos Livres/genética
3.
Prenat Diagn ; 42(8): 1008-1014, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35441712

RESUMO

OBJECTIVE: To decrease the false-positive rate of NIPT using cell-free fetal DNA (cffDNA) fraction enrichment and the simulated confined placental mosaicism proportion (SCPMP) threshold application via cffDNA quantification. METHOD: Using a cffDNA enrichment method, 303 plasma samples with positive NIPT results (Z-score > 3.0; 200 true-positive and 103 false-positive cases) were re-sequenced. A method to calculate the SCPMP based on the quantified cffDNA fraction was developed; the SCPMP threshold between true- and false-positive NIPT results was determined and used for re-analyses. RESULTS: With enrichment, the fetal fraction of the 303 samples was 26.9 ± 8.4%, compared to 11.0 ± 3.2% without enrichment. The optimized threshold method with double determination using the Z-value-defined SCPMP can reduce the false-positive rates for trisomies 21, 18, and 13 by 87%, 80%, and 88.9%, respectively. CONCLUSION: Our optimized method can decrease the false-positive rate of NIPT results.


Assuntos
Ácidos Nucleicos Livres , Ácidos Nucleicos Livres/genética , DNA , Feminino , Humanos , Mosaicismo , Placenta , Gravidez , Diagnóstico Pré-Natal/métodos
4.
Am J Obstet Gynecol ; 224(3): 300.e1-300.e9, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32871130

RESUMO

BACKGROUND: Noninvasive monitoring of fetal development and the early detection of pregnancy-associated complications is challenging, largely because of the lack of information about the molecular spectrum during pregnancy. Recently, cell-free DNA in plasma was found to reflect the global nucleosome footprint and status of gene expression and showed potential for noninvasive health monitoring during pregnancy. OBJECTIVE: We aimed to test the relationships between plasma cell-free DNA profiles and pregnancy biology and evaluate the use of a cell-free DNA profile as a noninvasive method for physiological and pathologic status monitoring during pregnancy. STUDY DESIGN: We used genome cell-free DNA sequencing data generated from noninvasive prenatal testing in a total of 2937 pregnant women. For each physiological and pathologic condition, features of the cell-free DNA profile were identified using the discovery cohort, and support vector machine classifiers were built and evaluated using independent training and validation cohorts. RESULTS: We established nucleosome occupancy profiles at transcription start sites in different gestational trimesters, demonstrated the relationships between gene expression and cell-free DNA coverage at transcription start sites, and showed that the cell-free DNA profiles at transcription start sites represented the biological processes of pregnancy. In addition, using cell-free DNA data, nucleosome profiles of transcription factor binding sites were identified to reflect the transcription factor footprint, which may help to reveal the molecular mechanisms underlying pregnancy. Finally, by using machine-learning models on low-coverage noninvasive prenatal testing data, we evaluated the use of cell-free DNA nucleosome profiles for distinguishing gestational trimesters, fetal sex, and fetal trisomy 21 and highlighted its potential utility for predicting physiological and pathologic fetal conditions by using low-coverage noninvasive prenatal testing data. CONCLUSION: Our analyses profiled nucleosome footprints and regulatory networks during pregnancy and established a noninvasive proof-of-principle methodology for health monitoring during pregnancy.


Assuntos
Expressão Gênica , Teste Pré-Natal não Invasivo , Complicações na Gravidez/sangue , Complicações na Gravidez/genética , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudo de Prova de Conceito , Adulto Jovem
5.
Biochem Biophys Res Commun ; 501(2): 428-433, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29738762

RESUMO

Cervical cancer (CC) is one of the most prevalent malignances among women. However, the mechanism underlying CC development remains elusive. Recently, circular RNAs (circRNAs) have been known as important regulators in tumorigenesis. Whether circRNAs are involved in CC requires to be determined. In the present study, we found that circRNA hsa_circ_0023404 was significantly upregulated in CC tissues compared to adjacent normal tissues. And its overexpression was correlated with poor prognosis in CC patients. Functionally, we showed that knockdown of hsa_circ_0023404 significantly suppressed the proliferation, arrested the cell-cycle progression and inhibited cell migration and invasion in CC. In terms of mechanism, we found that hsa_circ_0023404 acted as a sponge of miR-136 and miR-136 targeted TFCP2, which is an activator of YAP signaling pathway. We showed that hsa_circ_0023404 activated YAP pathway in CC via promoting TFCP2 expression by sponging miR-136, leading to CC development and progression. Taken together, our study for the first time demonstrated the pivot role of hsa_circ_0023404 and revealed a novel regulatory loop of hsa_circ_0023404/miR-136/TFCP2/YAP axis in CC progression.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Prognóstico , Transdução de Sinais/genética , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Proteínas de Sinalização YAP
6.
Biomarkers ; 22(3-4): 291-295, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27775434

RESUMO

To investigate whether resistin is associated with early atherosclerosis in male smokers. The present study consecutively enrolled 50 male smokers. Their serum resistin contents were detected with enzyme linked immunosorbent assay (ELISA), and subclinical atherosclerosis indices, including carotid inner middle thickness (IMT) and arterial elasticity indices (C1 and C2), were measured. The association between serum resistin levels and IMT, C1 and C2 were respectively evaluated with the Pearson's correlation coefficient method. The results showed that the serum resistin level had a positive association with IMT (r = 0.307, p = .030), but were both inversely associated with C1 (r = -0.440, p = .001) and C2 (r = -0.381, p = .006). These associations remained significant even after adjustment for cardiovascular confounders. In conclusion, serum resistin concentration was independently associated with early atherosclerosis in male smokers.


Assuntos
Aterosclerose/diagnóstico , Resistina/sangue , Fumar/efeitos adversos , Artérias/fisiologia , Aterosclerose/sangue , Aterosclerose/etiologia , Espessura Intima-Media Carotídea , Elasticidade , Humanos , Masculino , Pessoa de Meia-Idade
8.
J Assist Reprod Genet ; 32(11): 1643-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26354096

RESUMO

PURPOSE: Idiopathic asthenospermia is the most common type of male infertility. Although the mechanisms causing asthenospermia are complex, recent studies have indicated an important role of cation channel of sperm (CATSPER) gene downregulation or abnormality in the etiology of idiopathic asthenospermia. METHODS: In the present study, 192 patients with idiopathic asthenospermia and 288 healthy controls were enrolled, and a flight mass spectrometry using Sequenom's MassArray biochip system was applied for genotyping 16 CATSPER gene SNPs reported in the human single nucleotide polymorphism (SNP) database. RESULTS: Our results indicated a correlation between CATSPER1 SNPs and idiopathic asthenospermia. In particular, the exonal SNP rs1893316 in CATSPER1 significantly correlated with idiopathic asthenospermia risk and is a potential important factor in determining an individual's genetic susceptibility to idiopathic asthenospermia. CONCLUSION: These finding will help to further elucidate the role of CATSPER1 in idiopathic asthenospermia pathogenesis.


Assuntos
Astenozoospermia/genética , Canais de Cálcio/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Canais de Cálcio/metabolismo , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Espermatozoides/metabolismo
9.
Int J Mol Sci ; 16(2): 4121-35, 2015 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-25689428

RESUMO

Exposure to high levels of estrogen is considered an important risk factor for susceptibility to breast cancer. Common polymorphisms in genes that affect estrogen levels may be associated with breast cancer risk, but no comprehensive study has been performed among Han Chinese women. In the present study, 32 single-nucleotide polymorphisms (SNPs) in estrogen-related genes were genotyped using the MassARRAY IPLEX platform in 1076 Han Chinese women. Genotypic and allelic frequencies were compared between case and control groups. Unconditional logistic regression was used to assess the effects of SNPs on breast cancer risk. Associations were also evaluated for breast cancer subtypes stratified by estrogen receptor (ER) and progesterone receptor (PR) status. Case-control analysis showed a significant relation between heterozygous genotypes of rs700519 and rs2069522 and breast cancer risk (OR = 0.723, 95% CI = 0.541-0.965, p = 0.028 and OR = 1.500, 95% CI = 1.078-2.087, p = 0.016, respectively). Subgroup comparisons revealed that rs2446405 and rs17268974 were related to ER status, and rs130021 was associated with PR status. Our findings suggest that rs700519 and rs2069522 are associated with susceptibility to breast cancer among the Han Chinese population and have a cumulative effect with three other identified SNPs. Further genetic and functional studies are needed to identify additional SNPs, and to elucidate the underlying molecular mechanisms.


Assuntos
Povo Asiático/genética , Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Adulto , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , China/etnologia , Estrogênios/genética , Estrogênios/metabolismo , Feminino , Redes Reguladoras de Genes/genética , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Fatores de Risco
10.
Int J Mol Sci ; 15(2): 2130-41, 2014 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-24481062

RESUMO

The specific mechanism by which low-risk genetic variants confer breast cancer risk is currently unclear, with contradictory evidence on the role of single nucleotide polymorphisms (SNPs) in TOX3/LOC643714 as a breast cancer susceptibility locus. Investigations of this locus using a Chinese population may indicate whether the findings initially identified in a European population are generalizable to other populations, and may provide new insight into the role of genetic variants in the etiology of breast cancer. In this case-control study, 623 Chinese female breast cancer patients and 620 cancer-free controls were recruited to investigate the role of five SNPs in TOX3/LOC643714 (rs8051542, rs12443621, rs3803662, rs4784227, and rs3112612); Linkage disequilibrium (LD) pattern analysis was performed. Additionally, we evaluated how these common SNPs influence the risk of specific types of breast cancer, as defined by estrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER2) status. Significant associations with breast cancer risk were observed for rs4784227 and rs8051542 with odds ratios (OR) of 1.31 ((95% confidence intervals (CI), 1.10-1.57)) and 1.26 (95% CI, 1.02-1.56), respectively, per T allele. The T-rs8051542 allele was significantly associated with ER-positive and HER2-negative carriers. No significant association existed between rs12443621, rs3803662, and rs3112612 polymorphisms and risk of breast cancer. Our results support the hypothesis that the applicability of a common susceptibility locus must be confirmed among genetically different populations, which may together explain an appreciable fraction of the genetic etiology of breast cancer.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores de Progesterona/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Proteínas Reguladoras de Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , China , Feminino , Proteínas de Grupo de Alta Mobilidade , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Transativadores , Adulto Jovem
11.
Int J Mol Sci ; 15(4): 5446-57, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24686516

RESUMO

Recent genome-wide association studies (GWASs) have identified 15q25.1 as a lung cancer susceptibility locus. Here, we sought to explore the direct carcinogenic effects of genetic variants in this region on the risk of developing lung adenocarcinoma (ADC). Five common SNPs (rs8034191, rs16969968, rs1051730, rs938682, and rs8042374) spanning the 15q25.1 locus were assayed in a case-control study examining a cohort of 301 lung ADCs and 318 healthy controls. Stratification analysis by gender, smoking status, and tumor, node, metastasis (TNM) classification, was performed. In addition, sections from ADC tissue and normal tissue adjacent to tumors were stained with an anti-CHRNA3 (cholinergic receptor nicotinic α3) antibody by immunohistochemistry in 81 cases. Our results demonstrate that rs8042374, a variant of the CHRNA3 gene, is associated with an increased risk of ADC with an OR of 1.76 (95% CI: 1.17-2.65, p=0.024). This variant was linked to a greater risk of ADC in female nonsmokers (OR (95% CI): 1.81 (1.05-3.12), p=0.032) and female stage I+II cases (OR (95% CI): 1.92 (1.03-3.57), p=0.039). Although located within the same gene, rs938682 showed protective effects for smokers, stage III+IV cases, and male stage III+IV cases. Additionally, the CHRNA3 protein level in ADC tissue was slightly higher than in the surrounding normal lung tissue, based on immunohistochemical analysis. Our results suggest that the CHRNA3 polymorphism functions as a genetic modifier of the risk of developing lung ADC in the Chinese population, particularly in nonsmoking females.


Assuntos
Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Receptores Nicotínicos/genética , Adenocarcinoma de Pulmão , Adulto , Idoso , Anticorpos/imunologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Receptores Nicotínicos/biossíntese , Receptores Nicotínicos/imunologia , Fumar , Adulto Jovem
12.
Int J Gynaecol Obstet ; 167(1): 273-280, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38651210

RESUMO

OBJECTIVE: To evaluate non-invasive prenatal testing (NIPT) and expanded non-invasive prenatal testing (NIPT-plus) for detecting aneuploidies at different sequencing depths and assess Z-score accuracy in predicting trisomies 21, 18, 13, 45X, and 47XXX. METHODS: Pregnancies with positive NIPT or NIPT-plus results detected at the prenatal diagnosis center of Nanfang Hospital were included in this retrospective study, between January 2017 and December 2022. Invasive prenatal diagnostic results were collected. Logistic regression analyses were used to study the relationship between Z-score and positive predictive value (PPV). Optimal cut-off values were obtained based on receiver operating characteristic analysis, and PPVs were calculated in different groups. RESULTS: We evaluated 1348 pregnant women with positive results, including 930 reported by NIPT and 418 reported by NIPT-plus. NIPT reported significantly more rare chromosomal aneuploidies (RCAs), and NIPT-plus had a significantly higher PPV for trisomy 21 (T21). Logistic regression analyses showed a significant association (P < 0.001) between Z-score and PPVs for T21 and trisomy 18 (T18). A linear relationship was observed between fetal fraction (FF) and Z-values in the true positive cases of T21 and T18.The high Z-score group had significantly higher PPVs than the low Z-score group for T21, T18, trisomy 13, and 47XXX, but not for 45X. CONCLUSION: The Z-score is helpful in assessing NIPT or NIPT-plus results. Therefore, we suggest including the Z-score and FF in the results. By combining the Z-score, FF, and maternal age, clinicians can interpret NIPT results more accurately and improve personal counsel to reduce patients' anxiety.


Assuntos
Aneuploidia , Teste Pré-Natal não Invasivo , Valor Preditivo dos Testes , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Teste Pré-Natal não Invasivo/métodos , Transtornos Cromossômicos/diagnóstico , Trissomia/diagnóstico , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Curva ROC , Modelos Logísticos , Síndrome da Trissomia do Cromossomo 13/diagnóstico
13.
Gene ; 928: 148789, 2024 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-39047956

RESUMO

BACKGROUND: The expression profiles of placental genes are crucial for understanding the pathogenesis of fetal development and placental-origin pregnancy syndromes. However, owing to ethical limitations and the risks of puncture sampling, it is difficult to obtain placental tissue samples repeatedly, continuously, multiple times, or in real time. Establishing a non-invasive method for predicting placental gene expression profiles through maternal plasma cell-free DNA (cfDNA) sequencing, which carries information about the source tissue and gene expression, can potentially solve this problem. METHODS: Peripheral blood and placental samples were collected simultaneously from pregnant women who underwent cesarean section. Deep sequencing was performed on the separated plasma cfDNA and single-cell sequencing was performed on peripheral blood mononuclear cells (PBMC), chorioamniotic membranes (CAM), placental villi (PV), and decidua basalis (DB). The aggregation of corresponding information for each gene was combined with the transcriptome of PBMCs and a differential resolution transcriptome of the placenta. This combined information was then utilized for the construction of gene expression prediction models. After training, all models evaluated the correlation between the predicted and actual gene expression levels using external test set data. RESULTS: From five women, more than 20 million reads were obtained using deep sequencing for plasma cfDNA; PBMCs obtained 32,401 single-cell expression profiles; and placental tissue obtained 156,546 single-cell expression profiles (59,069, 44,921, and 52,556 for CAM, PV, and DB, respectively). The cells in the PBMC and placenta were clustered and annotated into five and eight cell types, respectively. A "DEPICT" gene expression prediction model was successfully constructed using deep neural networks. The predicted correlation coefficients were 0.75 in PBMCs, 0.84 in the placenta, and 0.78, 0.80, and 0.77 in CAM, BP, and PV respectively, and greater than 0.68 in different cell lines in the placenta. CONCLUSION: The DEPICT model, which can noninvasively predict placental gene expression profiles based on maternal plasma cfDNA fragmentation characteristics, was constructed to overcome the limitation of the inability to obtain real-time placental gene expression profiles and to improve research on noninvasive prediction of placental origin pregnancy syndrome.


Assuntos
Ácidos Nucleicos Livres , Leucócitos Mononucleares , Placenta , Humanos , Gravidez , Feminino , Ácidos Nucleicos Livres/genética , Placenta/metabolismo , Adulto , Leucócitos Mononucleares/metabolismo , Fragmentação do DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Transcriptoma , Perfilação da Expressão Gênica/métodos , Análise de Célula Única/métodos
14.
Acta Neuropsychiatr ; 25(6): 356-60, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25287876

RESUMO

OBJECTIVES: To investigate the relationships between single-nucleotide polymorphisms (SNPs) in NOTCH4 and brain-derived neurotrophic factor (BDNF) with schizophrenia among Han Chinese in Southern China. METHODS: Two NOTCH4 SNPs (rs520688 and rs415929) and two BDNF SNPs (rs2030324 and rs12273539) were examined in 464 schizophrenics and 464 healthy controls from Hunan province in South China, using the Sequenom MassARRAY® iPLEX System. RESULTS: In the study population, rs520688 and rs2030324 were significantly associated with schizophrenia. A decreased risk of schizophrenia was associated with the rs520688 GA genotype (p = 0.035), whereas an increased risk of schizophrenia was associated with the rs2030324 CC/CT genotype (p = 0.044). The genotype distributions of rs415929 in NOTCH4 and rs12273539 in BDNF did not differ significantly between the case and control groups. Although no allele-allele interactions were detected between rs520688 and rs2030324, recombination analysis revealed a combined effect of the two on the susceptibility to schizophrenia, with GA-TT decreasing and CT/CC-GG/GA increasing the risk of schizophrenia. CONCLUSION: In conclusion, rs520688 in NOTCH4 and rs2030324 in BDNF are significantly associated with schizophrenia among Han Chinese in Southern China. The two had a combined effect on the susceptibility to schizophrenia among Han Chinese in Southern China, but this may not be caused by an allele-allele interaction.

15.
Mol Biol Rep ; 39(10): 9557-62, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22740136

RESUMO

Recently, a genome-wide association study of gastric cancer (GC) reported the significant association of seven genetic variants (rs4072037 and rs4460629 on 1q22; rs753724, rs11187842, rs3765524, rs2274223, and rs3781264 on 10q23) with GC in a Chinese population. These findings were confirmed in a subsequent independent study. However, it remains unknown whether these loci are associated with an increased risk of colorectal cancer (CRC). This study was to test whether the seven single nucleotide polymorphisms (SNPs) associated with GC were also associated with CRC in a Chinese population. The seven SNPs were genotyped using MassARRAY system. Allelic, genotypic, and haplotypic associations of the SNPs with CRC were investigated using χ(2) tests and logistic regression analysis. The SNPs rs3765524 and rs2274223, located on 10q23, were found to have significant protective effects against CRC, with equal odds ratios per allele. The two SNPs located on 1q22 (rs4072037 and rs4460629) showed a weak association with CRC. No significant association was identified with CRC for the remaining three SNPs located on 10q23 (rs753724, rs11187842, and rs3781264). These results suggest that rs3765524 and rs2274223 on 10q23 are associated with a protective effect against CRC in a Chinese population.


Assuntos
Cromossomos Humanos Par 10/genética , Neoplasias Colorretais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Adulto Jovem
16.
Int J Mol Sci ; 13(7): 8364-8378, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22942708

RESUMO

DNA hypomethylation and/or hypermethylation are presumed to be early events in carcinogenesis, and one or more DNA methyltransferases (DNMTs) have been suggested to play roles in carcinogenesis of gastric cancer (GC). However, there have been no systematic studies regarding the association between DNMT gene polymorphisms and GC risk. Here, we examined the associations of 16 single nucleotide polymorphisms (SNPs) from DNMT1 (rs2114724, rs2228611, rs2228612, rs8101866, rs16999593), DNMT2 (rs11695471, rs11254413), DNMT3A (rs1550117, rs11887120, rs13420827, rs13428812, rs6733301), DNMT3B (rs2424908, rs2424913, rs6087990) and DNMT3L (rs113593938) with GC in the Southern Chinese population. We assessed the associations of these 16 SNPs with GC in a case-control study that consisted of 242 GC cases and 294 controls, using the Sequenom MALDI-TOF-MS platform. Association analyses based on the χ(2) test and binary logistic regression were performed to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. We found that rs16999593 in DNMT1, rs11254413 in DNMT2 and rs13420827 in DNMT3A were significantly associated with GC susceptibility (OR 1.45, 0.15, 0.66, respectively; 95% CI 1.00-2.11, p = 0.047; 0.08-0.27, p < 0.01; 0.45-0.97, p = 0.034, respectively, overdominant model). These results suggested that DNMT1, DNMT2 and DNMT3A may play important roles in GC carcinogenesis. However, further studies are required to elucidate the mechanism.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China , DNA (Citosina-5-)-Metiltransferase 1 , DNA Metiltransferase 3A , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Risco , Neoplasias Gástricas/enzimologia , Adulto Jovem
17.
Zhonghua Nan Ke Xue ; 18(4): 314-7, 2012 Apr.
Artigo em Zh | MEDLINE | ID: mdl-22574365

RESUMO

OBJECTIVE: To investigate the association of single nucleotide polymorphism (SNP) of the Protamine 1 (PRM1) gene in infertile men with teratozoospermia. METHODS: We collected semen samples from 157 infertile men with teratozoospermia (case group) and 37 age-matched male volunteers (control group), and subjected them to morphological analysis. We extracted genome DNA, genotyped the polymorphism of the PRM1-190C- > A SNP (rs2301365) using the Sequenom MassARRAY system, compared the genotype frequencies between the case and control groups, and analyzed the sperm morphological parameters of different genotypes in the infertile males with teratozoospermia. RESULTS: The frequencies of the genotypes CC, CA and AA were 38.9% (61), 44.6% (70) and 16.6% (26) in the case group, as compared with 45.9% (17), 51.4% (19) and 2.7% (1) in the control, with that of AA significantly higher in the patients than in the volunteers (P<0.05). The frequencies of the alleles C and A were 57.6% and 42.4% in the former, with no significant differences from 71.6% and 28.4% in the latter (P>0.05). Nor were any statistically significant differences observed in sperm morphology parameters between the genotype CC and CA, AA and CA + AA in the male patients (P>0.05). CONCLUSION: The SNP of PRM1-190C- > A might be associated with teratozoospermia-induced male infertility in the Han Chinese. Although this SNP may attribute to abnormal sperm morphology, the targeted part of sperm remains unclear.


Assuntos
Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Protaminas/genética , Espermatozoides/anormalidades , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Genótipo , Humanos , Masculino
18.
Chin J Cancer Res ; 24(1): 29-35, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23359760

RESUMO

OBJECTIVE: Genome-wide association studies (GWAS) have identified 11 loci that influence the risk of developing colorectal cancer (CRC). Given that these studies were conducted in European Caucasian populations, it is not clear whether the results are relevant for populations with different ethnicities. The aim of this study was to examine these associations in a southern Chinese population. METHODS: Eleven single-nucleotide polymorphisms (SNPs), rs12701937, rs16892766, rs7014346, rs6983267, rs719725, rs10795668, rs3802842, rs4444235, rs9929218, rs10411210, and rs961253, were genotyped in 229 CRC patients and 267 controls using the MassArray SNP genotyping system. RESULTS: Evidence of an association with CRC was found for four of the 11 loci. The strongest associations were with rs4444235 and rs961253, with significant odds ratios close to those reported in previous GWAS. Among these four loci, rs719725 and rs4444235 were significantly associated with female gender, rs3802842, rs961253, and rs4444235 with early disease onset, and rs3802842 with later disease onset. However, no associations with CRC risk were detected for six other loci (rs9929218, rs10411210, rs12701937, rs7014346, rs6983267, and rs10795668), and one SNP, rs16892766, was not polymorphic in any of the study participants. CONCLUSION: The rs4444235 and rs961253 loci are strongly associated with the risk of CRC in southern Chinese.

19.
Mol Cytogenet ; 15(1): 29, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794576

RESUMO

OBJECTIVE: Since 2011, noninvasive prenatal testing (NIPT) has undergone rapid expansion, with both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this testing tool are lacking. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations in order to inform pre- and post-test counseling, pre/perinatal decision making, and medical risk assessment/management. METHODS: This retrospective study included women referred for invasive prenatal diagnosis to confirm positive NIPT results between January 2017 and December 2020. Prenatal diagnosis testing, including karyotyping, chromosomal microarray analysis (CMA) were performed. Positive predictive values (PPVs) were calculated. RESULTS: In total, 468 women were recruited. The PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively. The PPVs for rare chromosomal abnormalities (RCAs) and copy number variants (CNVs) were 17.0% and 40.4%, respectively. The detection of sex chromosomal aneuploidies (SCAs) had a PPV of 20% for monosomy X, 23.5% for 47,XXX, 68.8% for 47,XXY, and 62.5% for 47,XYY. The high-risk groups had a significant increase in the number of true positive cases compared to the low- and moderate-risk groups. CONCLUSIONS: T13, monosomy X, and RCA were associated with lower PPVs. The improvement of cell-free fetal DNA screening technology and continued monitoring of its performance are important.

20.
Mol Biol Rep ; 38(8): 5093-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21221812

RESUMO

SMAD7 has been demonstrated to antagonize TGF-ß-mediated fibrosis, carcinogenesis, and inflammation. Two previous genome-wide association studies identified three single nucleotide polymorphisms (SNPs) (rs4939827, rs12953717 and rs4464148) in SMAD7 to be associated with colorectal cancer in a Western population. We conducted the first case-control study in a Han Chinese population to explore the associations between these three SNPs and colorectal, gastric, and lung cancers. Of the three SNPs, only rs12953717 was strongly associated with the three types of cancer, fitting the overdominant model. Compared with the CC/TT (CC combined with TT) genotype, the adjusted odds ratios for the CT genotype were 2.002 (95% CI, 1.250-3.207, P = 0.004), 1.678 (95% CI, 1.048-2.689, P = 0.031), 3.825 (95% CI, 2.310-6.335, P < 1 × 10(-4)), and 2.294 (95% CI, 1.537-3.343, P < 1 × 10(-4)), respectively, for colorectal, gastric, lung, and combined cancers. These outcomes suggest that rs12953717 is a common risk marker of these three types of cancer in the Han Chinese.


Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína Smad7/genética , Neoplasias Gástricas/genética , Estudos de Casos e Controles , China , Etnicidade/genética , Feminino , Estudos de Associação Genética , Genética Populacional , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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