Advances in the role of ion channels in leukemia.

Ion channels are widely present in cell membranes, serving as crucial pathways for the movement of ions enter and exit cells. Variations in the expression of ion channels are crucial for regulating cellular functions. Among the genes associated with leukemia, certain genes encode ion channels. When these ion channels experience dysfunction or changes in expression, they can impact the physiological functions and signal transduction of hematopoietic cells, thereby regulating leukemia cell proliferation, differentiation, invasion/migration, and apoptosis. This article will provide a comprehensive review of the research progress on the expression and function of various ion channels in leukemia, thoroughly exploring their roles and mechanisms in the onset and progression of the disease, providing new insights and ideas for identifying potential biomarkers and developing new treatment methods for leukemia, thereby promoting innovations in future leukemia diagnosis and therapy.

GIPC2 is a tumor suppressor gene for acute myeloid leukemia and induces apoptosis of leukemia cells by regulating the PI3K/AKT pathway.

Aims: To explore the expression and methylation levels of GIPC2 in acute myeloid leukemia (AML), discuss the mechanism of GIPC2 in AML and provide new strategies for the diagnosis and treatment of AML. Methods: qPCR, western blotting, cell counting kit-8 assay, bisulfite sequencing and other experiments were used in this study. Results: The expression of GIPC2 was found to be downregulated in AML and is mainly affected by DNA promoter methylation. Decitabine can demethylate the promoter region of GIPC2, and GIPC2 expression is upregulated after demethylation. Overexpression of GIPC2 in HL-60 cells can induce apoptosis by inhibiting the PI3K/AKT pathway. Conclusion: Our findings identify that GIPC2 is associated with the PI3K/AKT signaling pathway and may represent a potential therapeutic target and biomarker for the management of AML.

Trimethylamine N-Oxide Metabolites in Early Pregnancy and Risk of Gestational Diabetes: A Nested Case-Control Study.

OBJECTIVES: This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM). DESIGN: A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO. RESULTS: TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant. CONCLUSIONS: TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM.

A BAYESIAN GRAPHICAL MODEL FOR GENOME-WIDE ASSOCIATION STUDIES (GWAS).

The analysis of GWAS data has long been restricted to simple models that cannot fully capture the genetic architecture of complex human diseases. As a shift from standard approaches, we propose here a general statistical framework for multi-SNP analysis of GWAS data based on a Bayesian graphical model. Our goal is to develop a general approach applicable to a wide range of genetic association problems, including GWAS and fine-mapping studies, and, more specifically, be able to: (1) Assess the joint effect of multiple SNPs that can be linked or unlinked and interact or not; (2) Explore the multi-SNP model space efficiently using the Mode Oriented Stochastic Search (MOSS) algorithm and determine the best models. We illustrate our new methodology with an application to the CGEM breast cancer GWAS data. Our algorithm selected several SNPs embedded in multi-locus models with high posterior probabilities. Most of the SNPs selected have a biological relevance. Interestingly, several of them have never been detected in standard single-SNP analyses. Finally, our approach has been implemented in the open source R package genMOSS.

Genetic variants in the integrin gene predicted microRNA-binding sites were associated with the risk of prostate cancer.

microRNAs (miRNA) silence target genes through Watson-Crick based binding to the 3'untranslated regions (3'UTR). Thus, polymorphisms in the miRNA-binding sites may disrupt this process and play a potential role in cancer pathogenesis. Integrins have been implicated in the genesis and development of many tumors. This study was designed to evaluate the association between five SNP loci in predicted miRNA-binding sites in five integrin genes and prostate cancer occurrence and prognosis to provide data for screening high-risk Chinese Han individuals. These five polymorphisms were genotyped by using the high-resolution melting method (HRM) in 347 Chinese Han prostate cancer patients with long-time follow-up together with 367 age-matched healthy controls. GC carriers of rs11902171 in ITGAv were associated with a decreased risk of prostate cancer (OR 0.57, 95% CI 0.35-0.93). However, no significant difference was detected in genotype distributions of the five SNP loci in the progression-free survival time of prostate cancer. The ITGAv gene SNP rs11902171 may be potentially associated with the risk of prostate cancer.

Genetic variants in the microRNA machinery gene GEMIN4 are associated with risk of prostate cancer: a case-control study of the Chinese Han population.

Single-nucleotide polymorphisms located in the microRNA biogenesis pathway could alter the risk for developing prostate cancer. The present study was intended to identify common genetic variants responsible for prostate cancer susceptibility in the GEMIN4 gene. The high-resolution melting method was used to genotype seven polymorphisms (rs7813, rs4968104, rs3744741, rs2740348, rs1062923, rs910925, and rs910924) in the GEMIN4 gene in 300 prostate cancer patients and 244 matched controls. The encouraging discovery in this study was in the rs2740348. Patients carrying the variant heterozygote GC genotype in the rs2740348 were at a 36% decreased risk of prostate cancer (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.42, 0.99). Similarly, this variant allele carrier showed significant risk for prostate cancer (OR = 0.64). In addition, subjects carrying the homozygote TT genotype in the rs7813 had a significantly increased risk of prostate cancer (OR = 2.53, 95% CI = 1.07, 6.28). Two common haplotypes were found to be associated with decreased risk of prostate cancer. In the subgroup analysis, higher risk of more severity of prostate cancer (clinical stage III and IV) was observed in individuals with the rs7813 TT genotype (OR = 2.64, 95% CI = 1.02, 7.64), while lower risk of more severity of prostate cancer was observed in individuals with the rs3744741 T allele (OR = 0.69, 95% CI = 0.50, 0.96). Overall, our study provides substantial support for the association between the GEMIN4 gene and the risk of prostate cancer.

Association between promoter variants of interleukin-18 and schizophrenia in a Han Chinese population.

An increasing amount of evidence suggests that interleukin-18 (IL-18) plays a pivotal role in the pathophysiology of schizophrenia. However, association between single nucleotide polymorphism of IL-18 and the risk of schizophrenia has not been clarified. This study examined whether two promoter polymorphisms -137 G/C (rs187238) and -607 C/A (rs1946518) of IL-18 were associated with schizophrenia and six clinical symptoms (disorder of perception, thought disorder, disturbance of emotion, disorder of behavior and volition, suicide action, and aggressive action) to provide data for screening high-risk Han Chinese individuals. Three hundred seventy-two schizophrenic patients and 353 healthy controls from a Han Chinese population were examined to assess their genotype and allele frequencies of the two promoter polymorphisms of IL-18. The genotype distributions in both patients and controls were within Hardy-Weinberg equilibrium. No significant differences were observed in the genotype or the allele frequencies of the two single-nucleotide polymorphisms between patients and controls. However, genotype frequencies of -607 C/A showed significant differences between patients and controls in the appearance of perception disorder (χ2 = 6.153, p = 0.046). A significant difference was detected in -137 G/C between patients and controls in the appearance of aggressive action (χ2 = 3.909, p = 0.048). In conclusion, IL-18 gene promoter polymorphisms may not contribute to the susceptibility of schizophrenia in a Han Chinese population, but two single-nucleotide polymorphisms, -137 G/C and -607 C/A, may play a role in the development of perception disorder and aggressive action, respectively.