Gene polymorphisms as susceptibility factors in Brazilian asthmatic children and adolescents
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ABSTRACT:
SUBMITTER: Genov I
PROVIDER: S-EPMC4407241 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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Project description:Background: The association between vitamin D receptor (VDR) polymorphisms and the risk of asthma remains unclear. This study aimed to investigate the effect of VDR gene polymorphisms and VDR mRNA expression levels on respiratory function, nitric oxide levels in expiratory air, and serum vitamin D levels in children with asthma. Materials and Methods: The study included 80 healthy children (control group) and 100 asthmatic children (asthma group) between the age of 5 and 18 years. The VDR genotypes (ApaI, TaqI, and FokI) and VDR mRNA levels were determined in all groups. Results: There was no statistically significant difference in vitamin D levels between the asthma group and the control group (P > 0.05). A significant association was found between both genotype (CC) of the TaqI polymorphism [odds ratio (OR) = 0.2, 95% confidence interval (CI) (0.07-0.5), P = 0.003] and genotype (CA) of ApaI polymorphisms [OR = 0.2, 95% CI (0.07-0.8), P = 0.02], and asthma risk. In addition, when single-nucleotide polymorphism allelic frequencies between asthma and control groups were compared there is no significant association (P > 0.05). When compared to control group, VDR mRNA expression in asthma group decreased in genotypes CC and CA of ApaI and in genotypes TT and TC of TaqI (P < 0.05). Conclusion: The results provide supporting evidence for an association between TaqI and ApaI polymorphisms and asthma susceptibility.
| S-EPMC6733045 | biostudies-literature
Project description:BackgroundMulti-ethnicity of Brazilian population displays high levels of genomic diversity. Polymorphism may detect people at higher risk of developing cancer, distinctive response to treatment, and prognosis. Cyclooxygenase-2 (COX-2) is induced in response to growth factors and cytokines, and is expressed in inflammatory diseases, precancerous lesions and colorectal cancer (CRC). The aim of this study was to evaluate the influence of COX-2 -1195A > G and 8473T > C polymorphisms as a risk factor of developing CRC.MethodsWe evaluated COX-2 Single Nucleotide Polymorphism (SNP) of 230 CRC patients and 196 healthy controls by Real-Time Polymerase Chain Reaction.ResultsPopulations were in Hardy-Weinberg equilibrium (HWE), except for control group of 8473T > C SNP. The frequencies were similar in both groups for genotypes and haplotypes. There was no association between studied polymorphisms and risk of CRC.ConclusionsThe gene polymorphisms studied do not participate in the genetic susceptibility to CRC in a Brazilian population.
| S-EPMC5582032 | biostudies-literature
Project description:Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.
| S-EPMC7150445 | biostudies-literature
Project description:BackgroundWilms tumor, derived from embryonic cells, accounts for a large proportion of pediatric renal tumors. MYCN encoded by MYCN proto-oncogene, a member of the MYC family, is a BHLH transcription factor. It plays a critical role in tumorigenesis and predicts poor clinical outcomes in various types of cancer. However, the role of MYCN remained unclarified in Wilms tumor. In this study, we investigated the association between MYCN gene polymorphisms and Wilms tumor susceptibility.MethodsFour MYCN gene polymorphisms (rs57961569 G > A, rs9653226 T > C, rs13034994 A > G, and rs60226897 G > A) were genotyped in 183 cases and 603 controls. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between MYCN gene polymorphisms and Wilms tumor susceptibility.ResultsOverall, no significant association was found for any of the four MYCN gene polymorphisms. Interestingly, in the stratification analysis, the rs57961569 was found to be associated with decreased Wilms tumor susceptibility in the children older than 18 months (AOR = 0.65, 95% CI = 0.42-1.00, P = .050). Moreover, older children carrying 2-4 risk genotypes were at increased risk of Wilms tumor (OR = 1.55, 95% CI = 1.001-2.40, P = .0497). Haplotype GCAA was shown to significantly increased Wilms tumor risk (AOR = 2.40, 95% CI = 1.12-5.14, P = .024).ConclusionOur study demonstrated that these MYCN gene polymorphisms might be low penetrant variants in Wilms tumor.
| S-EPMC7938399 | biostudies-literature
Project description:BackgroundWilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m6A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility.MethodsA total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay.ResultAmong the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0-4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes.ConclusionsCollectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.
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Project description:While the influence of both genetic and environmental factors on the development of psychiatric symptoms is well-recognized, the precise nature of their interaction throughout development remains a subject of ongoing debate. This study investigated the association between the expression of 78 candidate genes, previously associated with psychiatric phenotypes, in peripheral blood and both adversity and psychopathology in a sample of 298 young individuals assessed at two time points from the Brazilian High Risk Cohort Study for Mental Conditions (BHRCS). Psychopathology was assessed using the Child Behavior Checklist (CBCL), considering the total CBCL, p-factor (i.e. general factor of psychopathology), and internalizing and externalizing symptoms as clinical variables. The life adversities considered in this study includes four composite variables: child maltreatment, stressful life events, threat and deprivation.Gene expression was measured using next-generation sequencing for target genes and differential gene expression was analyzed with the DESeq2 package. Mixed models revealed six genes associated with internalizing symptoms: NR3C1, HSPBP1, SIN3A, SMAD4, and CRLF3 genes exhibited a negative correlation with these symptoms, while FAR1 gene showed a positive correlation. Additionally, we also found a negative association between USP38 gene expression and externalizing symptoms. Finally, DENND11 and PRRC1 genes were negatively associated with deprivation, a latent factor characterized by neglect, parental absence, and measures of material forms of deprivation. No mediation or moderation effect was observed of gene expression on the association between life adversities and psychiatric symptoms, meaning that they might influence distinct pathways. Among these nine genes, NR3C1, which encodes a glucocorticoid receptor, is by far the most investigated, being associated with depressive symptoms, early life adversity, and stress. While further research is needed to fully understand the complex relationship between gene expression, life adversities, and psychopathology, our findings provide valuable insights into the molecular mechanisms underlying mental disorders.
2025-02-18 | GSE288870 | GEO
Project description:Incidence of hepatoblastoma has been increasing, but the causes of this disease remain unclear. Some studies have suggested that abnormal expressions of ALKBH5 gene are associated with multiple cancers. This study aims to test the hypothesis that hepatoblastoma risk may be modulated by genetic polymorphisms in ALKBH5 gene based on genotyped data from samples of 328 cases and 1476 controls enrolled from eight hospitals in China. We used TaqMan assay to genotype ALKBH5 gene single nucleotide polymorphisms (SNPs) rs1378602G > A and rs8400G > A. We calculated the odds ratios (ORs) and P values using logistic regression models to estimate the association between hepatoblastoma risk and ALKBH5 gene SNPs. We found the rs1378602G > A and rs8400G > A could not impact hepatoblastoma risk in single or combined analysis. Stratified analysis revealed that subjects with the rs8400 AA genotype are prone to getting hepatoblastoma in the clinical stage III + IV subgroup (adjusted OR = 1.93, 95% CI = 1.20-3.10, P=0.007), when compared to those with GG/GA genotype. False-positive report probability validated the reliability of the significant results. Preliminary functional annotations revealed that rs8400 A is correlated with increased expression of ALKBH5 gene in the expression quantitative trait locus (eQTL) analysis. In all, our investigation presents evidence of a weak impact of ALKBH5 gene polymorphisms on hepatoblastoma risk, using the largest hepatoblastoma sample size. These findings shed some light on the genetic basis of hepatoblastoma, implicating the role of ALKBH5 gene polymorphisms in the etiology of hepatoblastoma.
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Project description:Current knowledge on the etiology of hepatoblastoma remains limited. FTO gene has been documented as a susceptibility gene for several types of cancer. However, its role has not been characterized in hepatoblastoma. Herein, we intended to explore whether FTO gene single nucleotide polymorphisms (SNPs) contribute to the risk of hepatoblastoma. A multi-center case-control study was conducted including 358 cases and 1512 controls recruited from the night hospitals in China. Odds ratios (ORs) and 95% confidence intervals (CIs), for the association of FTO gene SNPs with hepatoblastoma risk, were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Four SNPs (rs1477196 G > A, rs9939609 T > A, rs7206790 C > G, and rs8047395 A > G) in the FTO gene were genotyped. We detected a significant association between rs9939609 T > A and decreased risk of hepatoblastoma (TA vs. TT: adjust OR = 0.73, 95% CI = 0.54-0.99, P = 0.041; TA/AA vs. TT: adjust OR = 0.73, 95% CI = 0.55-0.97, P = 0.032). Compared to 0-3 protective genotypes, carriers with four protective genotypes showed enough strength to protect from hepatoblastoma (adjust OR = 0.65, 95% CI = 0.47-0.91, P = 0.012). In stratification analysis, we also detected a significantly decreased risk of hepatoblastoma in subjects with rs9939609 TA/AA or with four protective genotypes in some subgroups. Our results provided some clues for an association of FTO gene SNPs with hepatoblastoma risk in Chinese children.Abbreviations: GWAS, genome-wide association study; FTO, The fat mass and obesity-associated gene; SNP, single nucleotide polymorphism; m6A, N6-methyladenosine; mRNA, messenger RNA; LD, linkage disequilibrium; HWE, Hardy-Weinberg equilibrium; OR, odds ratio; CI, confidence interval; AML, acute myeloid leukemia; GSC, glioblastoma stem(-like) cell; HER2, human epidermal growth factor receptor 2.
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Project description:Neuroblastoma (NB) is the most common extracranial tumor in children. YTHDC1, a member of RNA methylation modification binding proteins, plays critical roles in tumor occurrence and metastasis. However, it is unclear whether YTHDC1 gene polymorphisms are related to NB susceptibility. Herein, we aimed to evaluate the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C, rs3813832 T>C) and susceptibility of NB by logistic regression models. In this eight-center case-control study, 898 patients with NB and 1734 healthy controls were genotyped by TaqMan assay. The results showed that rs3813832 TC genotype could significantly reduce the susceptibility of NB compared with the TT genotype [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68-0.96, P = 0.018]. Combined genotype analysis revealed that individuals with 3 protective genotypes had a prominently lower NB risk than those with 0-2 protective genotypes (AOR = 0.80, 95% CI = 0.68-0.94, P = 0.006). The stratified analysis also demonstrated the protective effect of rs3813832 TC/CC and 3 protective genotypes in certain subgroups. Further functional experiments revealed that YTHDC1 siRNA-554, targeting the area near the rs3813832 T>C polymorphism site, could observably inhibit the proliferation and migration of NB cells. In conclusion, our findings highlight the involvement of YTHDC1 gene and its genetic variants in the etiology of NB.
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Project description:Neuroblastoma is a heterogeneous cancer frequently occurring in childhood. Germline mutations of PARP1 oncogene are implicated in several types of cancer. However, whether common single nucleotide polymorphisms (SNPs) in PARP1 gene are associated with neuroblastoma risk has received relatively few attentions. In this multi-center study, we aimed to elucidate the contributing role of PARP1 SNPs in neuroblastoma risk. We successfully genotyped three potentially functional PARP1 SNPs (rs1136410 A>G, rs2666428 T>C, rs8679 A>G) in 469 neuroblastoma cases and 998 controls. We did not detect any significant association between the analyzed SNPs and neuroblastoma risk in single SNP analysis. However, stratified analysis revealed that rs1136410 AG/GG carriers were more likely to develop tumors arising from mediastinum (AG/GG vs. AA: adjusted OR=1.65, 95% CI=1.06-2.56, P=0.028). Moreover, rs2666428 TC/CC carriers were at significantly lower risk to develop tumors from "other sites" (TC/CC vs. TT: adjusted OR=0.44, 95% CI=0.20-0.96, P=0.040). Our findings failed to provide evidence of the conferring role of the PARP1 gene polymorphisms in the risk of neuroblastoma. Further investigations of the association between PARP1 gene SNPs and neuroblastoma risk are warranted.
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