Correction: Association of Genetic Markers in the BCL-2 Family of Apoptosis-Related Genes with Endometrial Cancer Risk in a Chinese Population.
Ontology highlight
ABSTRACT:
SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC4309675 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Correction: Association of Genetic Markers in the BCL-2 Family of Apoptosis-Related Genes with Endometrial Cancer Risk in a Chinese Population.
PloS one 20150128 1
Similar Datasets
Project description:BackgroundIn vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies.Patients and methodsWe examined the relationship between BCL-2 gene family variants and endometrial cancer risk among 1,028 patients and 1,922 age-matched community controls from Shanghai, China. We also investigated possible interactions between genetic variants and established risk factors (demographic, lifestyle and clinical). Individuals were genotyped for 86 tagging single nucleotide polymorphisms (SNPs) in the BCL2, BAX, BAD and BAK1 genes.ResultsSignificant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend<0.05 for all). For SNPs rs17759659 and rs7243091 (minor allele for both: G), the associations were independent. The odds ratio was 1.27 (95% CI: 1.04-1.53) for women with AG genotype for the SNP rs17759659 and 1.82 (95% CI: 1.21-2.73) for women with the GG genotype for the SNP rs7243091. No interaction between these two SNPs and established non-genetic risk factors of endometrial cancer was noticed.ConclusionGenetic polymorphisms in the BCL2 gene may be associated with the risk of endometrial cancer in Chinese women.
| S-EPMC3634058 | biostudies-literature
Project description:BACKGROUND:Apoptosis is a normal physiological process in organs development, but excessive apoptosis is pathological and harmful. In previous studies, apoptosis-related genes are considered to be involved in the onset of osteoarthritis, but the mechanism is unclear. Therefore, we selected two common polymorphisms of apoptosis-related genes (BAX -248G>A, BCL2 -717C>A) to explore the relationship with osteoarthritis. METHODS:The two polymorphisms were genotyped by polymerse chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 134 cases with osteoarthritis and 142 controls. These genotypes distributions in controls were checked whether conformed to Hardy-Weinberg equilibrium (HWE). χ2 test was used to calculate odds ratio (OR) with corresponding 95% confidence interval (95% CI) which evaluated the strength of association between gene polymorphism and osteoarthritis susceptibility. RESULTS:The χ2 test showed that genotype frequencies of BAX -248G>A (rs4645878), BCL2 -717C>A (rs2279115) polymorphisms in control group were consistent with HWE. In BAX -248G>A polymorphism, compared with mutant genotype GA+AA, the common genotype GG increased the susceptibility to osteoarthritis significantly (OR=1.84, 95% CI=1.13-3.00), so G allele was (OR=1.76, 95% CI=1.16-2.68). The homozygous mutant genotype AA in BCL2 -717C>A carriers easily suffered from osteoarthritis in some condition, compared with CC genotype (P=0.03). A allele also increased 0.43 times risk of osteoarthritis development than C allele (OR=1.43, 95% CI=1.02-2.00). CONCLUSIONS:BAX -248G>A and BCL2 -717C>A polymorphisms may be the independent risk factors for the development of osteoarthritis.
| S-EPMC6958211 | biostudies-literature
Project description:The BCl-2 family has long been identified for its role in apoptosis. Following the initial discovery of BCL-2 in the context of B-cell lymphoma in the 1980s, a number of homologous proteins have since been identified. The members of the Bcl-2 family are designated as such due to their BCL-2 homology (BH) domains and involvement in apoptosis regulation. The BH domains facilitate the family members' interactions with each other and can indicate pro- or anti-apoptotic function. Traditionally, these proteins are categorised into one of the three subfamilies; anti-apoptotic, BH3-only (pro-apoptotic), and pore-forming or 'executioner' (pro-apoptotic) proteins. Each of the BH3-only or anti-apoptotic proteins has a distinct pattern of activation, localisation and response to cell death or survival stimuli. All of these can vary across cell or stress types, or developmental stage, and this can cause the delineation of the roles of BCL-2 family members. Added to this complexity is the presence of relatively uncharacterised isoforms of many of the BCL-2 family members. There is a gap in our knowledge regarding the function of BCL-2 family isoforms. BH domain status is not always predictive or indicative of protein function, and several other important sequences, which can contribute to apoptotic activity have been identified. While therapeutic strategies targeting the BCL-2 family are constantly under development, it is imperative that we understand the molecules, which we are attempting to target. This review, discusses our current knowledge of anti-apoptotic BCL-2 family isoforms. With significant improvements in the potential for splicing therapies, it is important that we begin to understand the distinctions of the BCL-2 family, not limited to just the mechanisms of apoptosis control, but in their roles outside of apoptosis.
| S-EPMC6384907 | biostudies-literature
Project description:To ascertain genetic diversity, population structure and linkage disequilibrium (LD) among a representative collection of Chinese winter wheat cultivars and lines, 90 winter wheat accessions were analyzed with 269 SSR markers distributed throughout the wheat genome. A total of 1,358 alleles were detected, with 2 to 10 alleles per locus and a mean genetic richness of 5.05. The average genetic diversity index was 0.60, with values ranging from 0.05 to 0.86. Of the three genomes of wheat, ANOVA revealed that the B genome had the highest genetic diversity (0.63) and the D genome the lowest (0.56); significant differences were observed between these two genomes (P<0.01). The 90 Chinese winter wheat accessions could be divided into three subgroups based on STRUCTURE, UPGMA cluster and principal coordinate analyses. The population structure derived from STRUCTURE clustering was positively correlated to some extent with geographic eco-type. LD analysis revealed that there was a shorter LD decay distance in Chinese winter wheat compared with other wheat germplasm collections. The maximum LD decay distance, estimated by curvilinear regression, was 17.4 cM (r(2)>0.1), with a whole genome LD decay distance of approximately 2.2 cM (r(2)>0.1, P<0.001). Evidence from genetic diversity analyses suggest that wheat germplasm from other countries should be introduced into Chinese winter wheat and distant hybridization should be adopted to create new wheat germplasm with increased genetic diversity. The results of this study should provide valuable information for future association mapping using this Chinese winter wheat collection.
| S-EPMC3434133 | biostudies-other
Project description:The Finnish population in Northern Europe has been a target of extensive genetic studies during the last decades. The population is considered as a homogeneous isolate, well suited for gene mapping studies because of its reduced diversity and homogeneity. However, several studies have shown substantial differences between the eastern and western parts of the country, especially in the male-mediated Y chromosome. This divergence is evident in non-neutral genetic variation also and it is usually explained to stem from founder effects occurring in the settlement of eastern Finland as late as in the 16th century. Here, we have reassessed this population historical scenario using Y-chromosomal, mitochondrial and autosomal markers and geographical sampling covering entire Finland. The obtained results suggest substantial Scandinavian gene flow into south-western, but not into the eastern, Finland. Male-biased Scandinavian gene flow into the south-western parts of the country would plausibly explain the large inter-regional differences observed in the Y-chromosome, and the relative homogeneity in the mitochondrial and autosomal data. On the basis of these results, we suggest that the expression of 'Finnish Disease Heritage' illnesses, more common in the eastern/north-eastern Finland, stems from long-term drift, rather than from relatively recent founder effects.
| S-EPMC2986642 | biostudies-other
Project description:The B-cell lymphoma-2 (Bcl-2) family is a group of genes regulating intrinsic apoptosis, a process controlling events such as development, homeostasis and the innate and adaptive immune responses in metazoans. In higher organisms, Bcl-2 proteins coordinate intrinsic apoptosis through their regulation of the integrity of the mitochondrial outer membrane; this function appears to have originated in the basal metazoans. Bcl-2 genes predate the cnidarian-bilaterian split and have been identified in porifera, placozoans and cnidarians but not ctenophores and some nematodes. The Bcl-2 family is composed of two groups of proteins, one with an α-helical Bcl-2 fold that has been identified in porifera, placozoans, cnidarians, and almost all higher bilaterians. The second group of proteins, the BH3-only group, has little sequence conservation and less well-defined structures and is found in cnidarians and most bilaterians, but not porifera or placozoans. Here we examine the evolutionary relationships between Bcl-2 proteins. We show that the structures of the Bcl-2-fold proteins are highly conserved over evolutionary time. Some metazoans such as the urochordate Oikopleura dioica have lost all Bcl-2 family members. This gene loss indicates that Bcl-2 regulated apoptosis is not an absolute requirement in metazoans, a finding mirrored in recent gene deletion studies in mice. Sequence analysis suggests that at least some Bcl-2 proteins lack the ability to bind BH3-only antagonists and therefore potentially have other non-apoptotic functions. By examining the foundations of the Bcl-2 regulated apoptosis, functional relationships may be clarified that allow us to understand the role of specific Bcl-2 proteins in evolution and disease.
| S-EPMC8998228 | biostudies-literature
Project description:The BCL-2 family protein BCL-RAMBO, also known as BCL2-like 13, anchors at the outer mitochondrial membrane and regulates apoptosis, mitochondrial fragmentation, and mitophagy. However, the mechanisms underlying the proapoptotic role of BCL-RAMBO remain unclear. In the present study, we demonstrated that BCL-RAMBO interacted with glucose-regulated protein 75 (GRP75), also known as heat shock protein family A member 9, and mortalin using co-immunoprecipitation and glutathione S-transferase-based pull-down assays. BCL-RAMBO interacted with GRP75 via its No BCL-2 homology domain. The interaction between BCL-RAMBO and GRP75 was confirmed by genetic interactions in Drosophila because a rough eye phenotype caused by the ectopic expression of BCL-RAMBO was partially suppressed by mutations in Hsc70-5, a mammalian GRP75 ortholog. In human embryonic kidney 293T cells, the co-expression of BCL-RAMBO and GRP75 facilitated an elevation in executioner caspase activity and poly (ADP-ribose) polymerase 1 (PARP-1) cleavage. In contrast, the knockdown of GRP75 suppressed elevated executioner caspase activity and PARP-1 cleavage in BCL-RAMBO-transfected cells. The mitochondrial release of cytochrome c induced by BCL-RAMBO was also attenuated by the knockdown of GRP75. These results indicate that GRP75 interacts with BCL-RAMBO and plays a crucial role in the BCL-RAMBO-dependent apoptosis signaling pathway.
| S-EPMC10462657 | biostudies-literature
Project description:Bcl-2 family proteins play a central role in regulating apoptosis. We previously reported that human Bcl-rambo, also termed BCL2L13, localized to mitochondria and induced apoptosis when overexpressed in human embryonic kidney 293T cells. However, the physiological function of Bcl-rambo currently remains unclear. In the present study, human Bcl-rambo was ectopically expressed in Drosophila melanogaster. Bcl-rambo mainly localized to the mitochondria of Drosophila Schneider 2 (S2) cells. The overexpression of Bcl-rambo, but not Bcl-rambo lacking a C-terminal transmembrane domain, induced apoptosis in S2 cells. Moreover, the ectopic expression of Bcl-rambo by a GAL4-UAS system induced aberrant morphological changes characterized by atrophied wing, split thorax, and rough eye phenotypes. Bcl-rambo induced the activation of effector caspases in eye imaginal discs. The rough eye phenotype induced by Bcl-rambo was partly rescued by the co-expression of p35, Diap1, and Diap2. By using this Drosophila model, we showed that human Bcl-rambo interacted genetically with Drosophila homologues of adenine nucleotide translocators and the autophagy-related 8 protein. The results of the present study demonstrated that human Bcl-rambo localized to mitochondria and at least regulated an apoptosis signaling pathway in Drosophila.
| S-EPMC4922555 | biostudies-literature
Project description:Although genetic variations in cell-cycle control genes have been previously linked to cancer risk, no study has specifically evaluated the role of these gene variants in endometrial carcinogenesis. Using data from the Shanghai Endometrial Cancer Study, a population-based case-control study with 1,199 cases and 1,212 age-matched controls (1997-2003), the authors carried out a systematic evaluation of the association of cell-cycle control genes with endometrial cancer risk. Sixty-five tagging or potentially functional single nucleotide polymorphisms in the CCNB1, CCND1, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, and CDKN2A genes were genotyped and evaluated. Three single nucleotide polymorphisms in the CDKN1B gene (rs11055027, rs3759216, and rs34330) were related to endometrial cancer risk, although only the association with rs34330 remained statistically significant after adjustment for multiple comparisons. The odds ratios for rs34330 were 1.33 (95% confidence interval (CI): 1.06, 1.66) and 1.51 (95% CI: 1.16, 1.94) for the CT and TT genotypes, respectively, compared with the CC genotype. In vitro luciferase reporter assays showed that the minor allele (A) in rs3759216, which was associated with decreased endometrial cancer risk (odds ratio = 0.73, 95% CI: 0.56, 0.94) without adjustment for multiple comparisons, significantly increased promoter activity. These findings suggest that polymorphisms of the CDKN1B gene may play a role in endometrial carcinogenesis.
| S-EPMC3101066 | biostudies-literature
Project description:During endochondral ossification, chondrocytes undergo hypertrophic differentiation and die by apoptosis. The level of inorganic phosphate (P(i)) elevates at the site of cartilage mineralization, and when chondrocytes were treated with P(i), they underwent rapid apoptosis. Gene silencing of the proapoptotic Bcl-2 homology 3-only molecule bnip3 significantly suppressed P(i)-induced apoptosis. Conversely, overexpression of Bcl-xL suppressed, and its knockdown promoted, the apoptosis of chondrocytes. Bnip3 was associated with Bcl-xL in chondrocytes stimulated with P(i). Bcl-xL was expressed uniformly in the growth plate chondrocytes, whereas Bnip3 expression was exclusively localized in the hypertrophic chondrocytes. Finally, we generated chondrocyte-specific bcl-x knock-out mice using the Cre-loxP recombination system, and we provided evidence that the hypertrophic chondrocyte layer was shortened in those mice because of an increased apoptosis of prehypertrophic and hypertrophic chondrocytes, with the mice afflicted with dwarfism as a result. These results suggest the pivotal role of Bcl-2 family members in the regulation of chondrocyte apoptosis.
| S-EPMC2546555 | biostudies-literature