Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population.

BACKGROUND: Human apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China. METHODS: A total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis. RESULTS: The present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04-3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22-5.23). CONCLUSIONS: Individuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.

Identification of lncRNA-associated differential subnetworks in oesophageal squamous cell carcinoma by differential co-expression analysis.

Differential expression analysis has led to the identification of important biomarkers in oesophageal squamous cell carcinoma (ESCC). Despite enormous contributions, it has not harnessed the full potential of gene expression data, such as interactions among genes. Differential co-expression analysis has emerged as an effective tool that complements differential expression analysis to provide better insight of dysregulated mechanisms and indicate key driver genes. Here, we analysed the differential co-expression of lncRNAs and protein-coding genes (PCGs) between normal oesophageal tissue and ESCC tissues, and constructed a lncRNA-PCG differential co-expression network (DCN). DCN was characterized as a scale-free, small-world network with modular organization. Focusing on lncRNAs, a total of 107 differential lncRNA-PCG subnetworks were identified from the DCN by integrating both differential expression and differential co-expression. These differential subnetworks provide a valuable source for revealing lncRNA functions and the associated dysfunctional regulatory networks in ESCC. Their consistent discrimination suggests that they may have important roles in ESCC and could serve as robust subnetwork biomarkers. In addition, two tumour suppressor genes (AL121899.1 and ELMO2), identified in the core modules, were validated by functional experiments. The proposed method can be easily used to investigate differential subnetworks of other molecules in other cancers.

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients.

OBJECTIVE: To investigate the prevalence of BRCA1/2 gene variants and evaluate the clinical and pathological characteristics associated with these variants in Chinese Hakka breast cancer patients. METHODS: A total of 409 breast cancer patients were analyzed based on next-generation sequencing results, with 337 categorized as non-carriers and 72 as carriers of BRCA1/2 variants. Data on the patients' BRCA1/2 gene mutation status, clinical and pathological characteristics, as well as menstrual and reproductive information, were collected, analyzed, compared, and tabulated. Logistic regression analysis was performed to explore the relationship between clinical characteristics and pathogenic variants. RESULTS: Among the patients, 72 were identified as carriers of pathogenic or likely pathogenic variants in BRCA1/2, while 337 had likely benign or benign mutations. The BRCA1 c.2635G > T (p. Glu879*) variant was detected at a high frequency, accounting for 12.5% (4/32) of the BRCA1 mutations, while the c.5164_5165del (p.Ser1722Tyrfs*4) variant was common among the BRCA2 mutations, accounting for 17.5% (7/40). It was observed that a higher proportion of BRCA1 carriers had the triple-negative breast cancer subtype, whereas more BRCA2 carriers exhibited estrogen receptor (ER) + and progesterone receptor (PR) + subtypes. Multivariate logistic regression analysis revealed that a family history of cancer (OR = 2.36, 95% CI = 1.00-5.54), bilateral cancer (OR = 4.78, 95% CI 1.61-14.20), human epidermal growth factor receptor 2 (HER2)- (OR = 8.23, 95% CI 3.25-20.84), and Ki67 ≥ 15% (OR = 3.88, 95% CI 1.41-10.65) were associated with BRCA1/2 mutations, with the age at diagnosis, age at menarche, and premenopausal status serving as covariates. CONCLUSIONS: The most common pathogenic variant of the BRCA1 and BRCA2 in breast cancer patients was c.2635G > T and c.5164_5165del, respectively. Additionally, a family history of cancer, bilateral cancer, HER2-, and Ki67 ≥ 15% were identified as independent predictors of BRCA1/2 pathogenic variants.

Association of Apolipoprotein E Gene Polymorphism with Type 2 Diabetic Nephropathy in the Southern Chinese Population.

Background: Common polymorphisms within the apolipoprotein E (APOE) gene are rs429358 and rs7412, which result in three major alleles (ɛ2, ɛ3, and ɛ4) and six genotypes (E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4). Although APOE gene polymorphisms have been suggested to be associated with the development of diabetic nephropathy (DN), their potential association remains unclear in different regions. This study aims to unveil the genetic effects of APOE gene polymorphisms on DN susceptibility and serum lipid profiles in southern Chinese population. Methods: A total of 306 DN patients and 483 type 2 diabetic patients as controls were included in the study. The APOE gene polymorphisms were analyzed by polymerase chain reaction (PCR) microarray gene chip. Relevant medical records and information of these participants were collected. Results: There were statistically significant differences (p < 0.05) in gender, SBP, hypertension, hyperuricemia, UTP, TG and HDL-C between DN patients and controls. DN patients exhibited a higher frequency of the ε2 allele and E2/E3 genotype than controls (p < 0.001). Logistic regression analysis indicated that the ε2 allele and E2/E3 genotype were independent risk factors (adjusted OR: 3.237, 95% CI: 1.789-5.854, p < 0.001; adjusted OR: 3.453, 95% CI: 1.873-6.368, p < 0.001), while the ε3 allele or E3/E3 genotype might serve as protective role (adjusted OR: 0.395, 95% CI: 0.255-0.612, p < 0.001) for development of DN. Conclusion: Our study indicates a correlation between APOE polymorphisms and DN in the southern Chinese Hakka population. Specifically, individuals carrying the APOE ε2 allele and E2/E3 genotype are at a higher risk of developing DN. Conversely, those with the APOE ε3 allele and E3/E3 genotype have a lower risk of DN in southern Chinese population.

T cell co-stimulator inducible co-stimulatory (ICOS) exerts potential anti-atherosclerotic roles through downregulation of vascular smooth muscle phagocytosis and proliferation.

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease. The role of the immune system in the etiology of the disease, particularly T cells, has been widely studied and is well established. T cell activation directly regulates co-signaling molecules present in immune synapses. Targeting one or several of these co-signaling molecules can inhibit T cell-mediated inflammation and delay or reduce AS. In recent years, this strategy has increasingly become a research focus. As such, we explored the role and therapeutic potential of the T cell co-stimulatory molecule inducible co-stimulatory (ICOS) in AS. METHODS: We compared the expression of ICOS in early AS lesions occurring in ApoE-deficient (ApoE-KO) rats fed a fat-diet and wild type (WT) rats fed the same diet. Eight-week old ApoE-KO and WT rats [ApoE-KO(0) and WT(0)] were fed a high-fat diet for 16 weeks [ApoE-KO(16) and WT(16)]. ICOS expression in aortic tissues was analyzed by quantitative real-time PCR, western blot, and confocal microscopy. The effect of ICOS overexpression in a transfected human T cell line on the phagocytosis and proliferation of co-cultured human aortic smooth muscle cells (HASMCs) was studied in vitro. RESULTS: Compared with WT(0), ApoE-KO(0), and WT(16) rats, ICOS expression in ApoE-KO(16) rats was significantly down-regulated both at the mRNA and protein levels. In vitro experiments indicated that ICOS overexpression reduces phagocytosis and proliferation by HASMCs, and may therefore produce an anti-atherosclerotic effect. CONCLUSIONS: The immune synaptic co-signaling molecule ICOS has an anti-atherosclerotic effect through inhibition of HASMC phagocytosis and proliferation, and can be used to delay plaque formation during the early stages of AS.