Association of tumor necrosis factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: A meta-analysis of 14 case-control studies.

Although numerous studies have suggested the association between TNF-α-308G/A polymorphism and susceptibility to obstructive sleep apnea (OSA), the results remained controversial and ambiguous. We performed the present meta-analysis to derive a more precise estimation.The PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang databases, and Weipu databases (until January 8, 2022) were accessed to retrieve relevant articles. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were calculated using the STATA statistical software.Totally, fourteen studies involving 2595 cases and 2579 controls were enrolled in this meta-analysis. Pooled results demonstrated significant association between TNF-α-308G/A polymorphism and OSA risk for the overall population(allele model:OR = 1.87 [1.47, 2.38] (n = 14), dominant model: OR = 1.88[1.48, 2.39] (n = 14), recessive model:OR = 2.83 [2.00, 4.00] (n = 11), homozygous model:OR = 3.30 [2.32, 4.68] (n = 11), and heterozygous model:OR = 1.67 [1.36, 2.06] (n = 14); P<0.001, respectively).Subgroup analysis showed that in both Caucasians and Asians, the A allele conferred increased risk to OSA compared to the G allele (Caucasians: OR = 1.40[1.03, 1.90] (n = 5), P = 0.033, Asians: OR = 2.30 [1.62, 3.26] (n = 9), P< 0.001). In subgroup analysis restricted to hospital-based individuals, significant association between TNF-α-308G/A polymorphism and OSA risk was identified under each genetic model. Whereas, in population-based individuals, increased risk of OSA were only found in homozygous model (OR = 2.19[1.23, 3.90] (n = 3), P = 0.008) and recessive model (OR = 1.77 [1.00, 3.13] (n = 3), P = 0.048). There was a substantial between-study heterogeneity (I2 = 69.10%) across studies which was explained by source of control participants (P = 0.036) by meta-regression. The results of leave-one-out meta-analysis and publication bias suggested the reliability and stability of our results.This meta-analysis suggested that TNF-α-308A allele may be a risk factor for the development of OSA. However, large scale,multi-center and well-designed case-control studies are needed in the future.

Top 100 influential manuscripts in obstructive sleep apnea: a bibliometric analysis.

OBJECTIVE: This study aimed to explore the characteristics of the top 100 influential manuscripts on obstructive sleep apnea (OSA). METHODS: All manuscripts in English were searched from the Thomson Reuters Web of Science database by using OSA-related terms and ranked based on citation frequency. The top 100 influential manuscripts were selected and further analyzed by author, subject, journal, year of publication, country of origin, and institution. RESULTS: A total of 42,878 manuscripts were searched from the Web of Science. The top 100 influential manuscripts were published from 2005 to 2017, with a total citation frequency of 38,463 and a median citation frequency of 303 (range: from 210 to 2, 707). The American Journal of Respiratory and Critical Care Medicine published the largest number of manuscripts from the top 100 (n = 18; 5340 citations), followed by Sleep (n = 11; 3516 citations) and Chest (n = 7; 1784 citations). The most cited manuscript (Marin, J.M et al., Lancet 2005; 2707 citations) mainly analyzed long-term cardiovascular outcomes in men with OSA with/without continuous positive airway pressure. The most prevalent subject was associated diseases (n = 41), followed by treatments (n = 40). Most of the manuscripts were original articles (n = 63) based on observational clinical studies and published from American institutions (n = 60). CONCLUSIONS: Our study identified the top 100 influential manuscripts on OSA and provides insights into the characteristics of the most highly cited manuscripts to improve our understanding and management of OSA.

Obstructive sleep apnea and incidence of malignant tumors: a meta-analysis.

OBJECTIVES: This paper assessed the connection between obstructive sleep apnea (OSA) and the incidence of malignant tumors. METHODS: PubMed, Cochrane, Scopus, Health Source Nursing Academic Edition, EMBASE, and Web of Sciences were searched until the date of July 25, 2020. The analysis included an assessment of the overall incidence of OSA malignancies, the incidence of OSA malignancies by age and gender, and the incidence of different types of malignancies in patients with OSA. The total rate and the corresponding 95% confidence interval (CI) of the incidence of malignant tumors in patients with OSA were calculated. Patients with OSA were classified according to age, gender, and different types of malignant tumors for meta-analysis. RESULTS: A total of 12 studies involving 862,820 participants were included in this meta-analysis. Random effect model analysis showed that the total incidence of malignant tumors in patients with OSA was 0.046% (95% CI: 0.027-0.065, P < 0.001), higher than that of malignant tumors in the general population. According to the analytical results classified by gender, the incidence of malignant tumor in female patients with OSA was 4.0% (95% CI: 0.014-0.066), higher than that in male patients at 3.5% (95% CI: 0.012-0.058). The analytical results classified by age showed that the incidence of malignant tumors in patients with OSA aged below 60 years was 1.8% (95% CI: 0.000-0.036), lower than that in patients aged above 60 years at 4.3% (95% CI: 0.002-0.084). The analytical results classified by the types of malignant tumors showed that the incidences of breast cancer, lung cancer, colorectal cancer, prostate cancer, kidney cancer, pancreatic cancer, and melanoma in patients with OSA were 0.5% (95% CI: 0.001-0.008), 0.5% (95% CI: 0.002-0.009), 0.5% (95% CI: 0.003-0.008), 1.1% (95% CI: 0.002-0.021), 0.3% (95% CI: 0.001-0.005), 0.1% (95% CI: 0.001-0.002), and 0.4% (95% CI: 0.003-0.005), respectively. Among them, the incidence of prostate cancer was the highest, followed by breast cancer, lung cancer, colorectal cancer, melanoma, and kidney cancer, whereas the incidence of pancreatic cancer was the lowest. However, the incidence of specific malignant tumors in patients with OSA did not have a significant increase compared with that in the general population. CONCLUSIONS: The analytical results of this meta-analysis suggested that OSA may be associated with an overall increase in the incidence of malignancies based on the currently available data, but the connection with specific types of malignancies was not significant. Further studies are needed to explore this association in the future.

Association between ERα gene Pvu II polymorphism and breast cancer susceptibility: A meta-analysis.

BACKGROUND: Estrogen has played an important role in the development of breast cancer. ER-α PvuII gene polymorphism is in close association with the occurrence risk of breast cancer, but no consensus has been achieved currently. METHODS: PubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang database, and VIP database were retrieved to collect the case-control studies on association between ERα gene Pvu II polymorphism and breast cancer risk published before September 1, 2017. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the literatures, Stata 14.0 software was applied for meta-analysis, and the pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The subgroup analysis was performed to assess the confounding factors, followed by assessment of publication bias and sensitivity analysis. RESULTS: A total of 26 studies were enrolled in the analysis based on inclusion criteria, which included 15,360 patients and 26,423 controls. The results demonstrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in 3 genetic models (C vs T, OR = 0.962, 95% CI = 0.933-0.992, P = .012; CC vs TT, OR = 0.911, 95% CI = 0.856-0.969, P = .003; CC vs TT/CT, OR = 0.923, 95% CI = 0.874-0.975, P = .004). Subgroup analysis was conducted on the basis of ethnicity and source of controls, whose results illustrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in Asians rather than in Caucasians (CC vs TT, OR = 0.862, 95% CI = 0.750-0.922, P = .038; CC vs TT/CT, OR = 0.851, 95% CI = 0.755-0.959, P = .008). In population-based subgroup rather than in hospital-based subgroup, ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in the allele model, homozygous model, dominant model, and recessive model (C vs T, OR = 0.943, 95% CI = 0.911-0.977, P = .001; CC vs TT, OR = 0.878, 95% CI = 0.817-0.944, P = .000; CC/CT vs TT, OR = 0.936, 95% CI = 0.881-0.994, P = .031; CC vs TT/CT, OR = 0.902, 95% CI = 0.847-0.960, P = .001). CONCLUSION: ERα gene Pvu II polymorphism exerts an important function in the progression of breast cancer.

TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway.

DNAX-activating protein of 12 kDa (DAP12) is a signaling adapter protein expressed in cells that participate in innate immune responses. By pairing with different triggering receptors expressed on myeloid cell (TREM) proteins, DAP12 can mediate both positive and negative cellular responses. In particular, TREM1 acts as an amplifier of the immune response, while TREM2 functions as a negative regulator. TREM2 has also been shown to stimulate the phagocytosis of apoptotic neurons and define the barrier function in microglia. Notably, loss-of-function mutations of either DAP12 or TREM2 result in a disorder known as Nasu-Hakola disease (NHD); and mutations of these genes have been associated with the risk for Alzheimer's disease (AD), suggesting that TREM2 and DAP12 may regulate common signaling pathways in the disease pathogenesis. In this study, we demonstrated an anti-inflammatory role of DAP12 in murine microglia that depends on the presence of TREM2. We also uncovered the JNK signaling pathway as the underlying molecular mechanism by which the TREM2/DAP12 complex suppresses the hyperactivation of microglia upon LPS stimulation. Interestingly, LPS down-regulates the expression of Trem2 via the activation of JNK and NF-κB signaling pathways, resulting in a vicious cycle that synergistically promotes the inflammatory responses. Our study provides insights into mechanism-based therapy for neuroinflammatory disorders.

Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P<0.05). The APOE ε3 group had slightly higher abnormal fasting plasma glucose values than did the APOE ε2 group (P = 0.065). Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05) and trended toward statistically significant correlation with diabetes (P = 0.082). The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052). Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of diabetes.

Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population.

Apolipoprotein E (apoE) mediates lipid metabolism both in peripheral and in the brain. The human APOE gene has three polymorphic alleles that influence the risk for various types of cancer and neurodegenerative diseases. A potential association between APOE allele and the risk for gastric cancer has been implicated, but the specific allele involved and potential associations with the subtype and the grade of cancer malignancy need further clarification. We screened the APOE genotype in 550 gastric cancer patients and 550 non-cancer control individuals and found that the presence of the APOE ε2 and lower serum total cholesterol are associated with an increased risk for gastric cancer (all P ≤ 0.0005). Interestingly, APOE ε2 is also correlated with increased risk for both intestinal and diffuse histotypes but not with TN classification or stage in gastric cancer patients, suggesting that APOE polymorphic alleles are associated with the risk of development but unlikely the progression of gastric cancer. Since ε2 carriers have lower levels of serum total cholesterol than non-ε2 carriers, our findings suggest that the increased risk for gastric cancer by APOE ε2 allele might be mediated through lowered serum total cholesterol levels.

Demographic and Lifestyle Characteristics, but Not Apolipoprotein E Genotype, Are Associated with Intelligence among Young Chinese College Students.

BACKGROUND: Intelligence is an important human feature that strongly affects many life outcomes, including health, life-span, income, educational and occupational attainments. People at all ages differ in their intelligence but the origins of these differences are much debated. A variety of environmental and genetic factors have been reported to be associated with individual intelligence, yet their nature and contribution to intelligence differences have been controversial. OBJECTIVE: To investigate the contribution of apolipoprotein E (APOE) genotype, which is associated with the risk for Alzheimer's disease, as well as demographic and lifestyle characteristics, to the variation in intelligence. METHODS: A total of 607 Chinese college students aged 18 to 25 years old were included in this prospective observational study. The Chinese revision of Wechsler Adult Intelligence Scale (the fourth edition, short version) was used to determine the intelligence level of participants. Demographic and lifestyle characteristics data were obtained from self-administered questionnaires. RESULTS: No significant association was found between APOE polymorphic alleles and different intelligence quotient (IQ) measures. Interestingly, a portion of demographic and lifestyle characteristics, including age, smoking and sleep quality were significantly associated with different IQ measures. CONCLUSIONS: Our findings indicate that demographic features and lifestyle characteristics, but not APOE genotype, are associated with intelligence measures among young Chinese college students. Thus, although APOE ε4 allele is a strong genetic risk factor for Alzheimer's disease, it does not seem to impact intelligence at young ages.

DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory Response.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a DAP12-associated receptor expressed in microglia, macrophages, and other myeloid-derived cells. Previous studies have suggested that TREM2/DAP12 signaling pathway reduces inflammatory responses and promotes phagocytosis of apoptotic neurons. Recently, TREM2 has been identified as a risk gene for Alzheimer disease (AD). Here, we show that DAP12 stabilizes the C-terminal fragment of TREM2 (TREM2-CTF), a substrate for γ-secretase. Co-expression of DAP12 with TREM2 selectively increased the level of TREM2-CTF with little effects on that of full-length TREM2. The interaction between DAP12 and TREM2 is essential for TREM2-CTF stabilization as a mutant form of DAP12 with disrupted interaction with TREM2 failed to exhibit such an effect. Silencing of either Trem2 or Dap12 gene significantly exacerbated pro-inflammatory responses induced by lipopolysaccharides (LPS). Importantly, overexpression of either full-length TREM2 or TREM2-CTF reduced LPS-induced inflammatory responses. Taken together, our results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses.