Association of the live microbe intake from foods with all-cause and cardiovascular disease-specific mortality: a prospective cohort study.

BACKGROUND: Live dietary microbes have been hypothesized to promoting human health. However, there has been lacking perceptions to crystallize nexus between consumption of foods with live microbes and mortality. OBJECTIVE: To investigate the association of consumption of foods with medium to high amounts of live microbes with all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. METHODS: The data were obtained from the National Health and Nutrition Examination Survey 1999-2018 at baseline linked to the 2019 National Death Index records. Based on consumption of foods that were categorized as either having medium or high microbial content (MedHi foods), participants were classified into three groups. Kaplan-Meier survival curves and multivariable Cox regression models were used to estimate the association of consumption of MedHi foods with mortality. Population-attributable fractions (PAFs) of consumption of MedHi foods in relation to mortality risk were also estimated. RESULTS: A total of 35,299 adults aged ≥ 20 years were included in this study. During a median follow-up of 9.67 years, compared with adults in G1, those in G3 had 16% (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.77-0.90) reduced risk of all-cause mortality, and 23% (HR, 0.77; 95% CI, 0.67-0.89) reduced risk of CVD-specific mortality. The PAF of high (G3) vs. intermediate or low consumption of MedHi foods (G1 + G2) with all-cause and CVD-specific mortality was 3.4% and 4.3%, respectively. CONCLUSIONS: Consumption of foods with higher microbial concentrations is associated with a reduced risk of all-cause and CVD-specific mortality in US adults.

Association of physical activity and dietary inflammatory index with overweight/obesity in US adults: NHANES 2007-2018.

BACKGROUND: Overweight and obesity lead to a range of noncommunicable diseases (NCDs), such as type 2 diabetes, cardiovascular disease, and stroke. Physical activity (PA) is an important lifestyle behavior for controlling body weight. Dietary inflammatory index (DII), which is associated with systemic inflammatory markers, is used to evaluate the potential of dietary inflammation. This is the first study to investigate the independent and joint associations of PA and DII with the risk of overweight/obesity among US adults. METHODS: Participants and data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007-2018, which is designed to examine the health and nutritional status of the non-institutionalized US population by a complex, multi-stage, probability sampling design. RESULTS: A total of 10723 US adults were selected. Physically active participants had lower overweight/obesity risk (total-time PA: OR = 0.756, 95% CI: 0.669-0.855; leisure-time PA: OR = 0.723, 95% CI: 0.643-0.813; and walk/bicycle-time PA: OR = 0.748, 95% CI: 0.639-0.875); however, those with work-time PA showed no significant association between PA and overweight/obesity. Compared with participants in the lowest DII group (Q1), those in the other three groups had high risks of overweight/obesity (Q2: OR = 1.218, 95% CI: 1.054-1.409; Q3: OR = 1.452, 95% CI: 1.245-1.693; Q4: OR = 1.763, 95% CI: 1.495-2.079). In joint analyses, PA was not eligible for reducing risks of weight/obesity if far more pro-inflammatory diet (Q4 of DII = 2.949-5.502) was taken in (total-time PA: OR = 1.725, 95% CI: 1.420-2.097; leisure-time PA: OR = 1.627, 95% CI: 1.258-2.105; walk/bicycle-time PA: OR = 1.583, 95% CI: 1.074-2.332; and work-time PA: OR = 1.919, 95% CI: 1.493-2.467). CONCLUSIONS: More leisure-time PA and walk/bicycle-time PA are associated with lower risk of overweight/obesity, and higher DII is associated with higher risk of overweight/obesity. In addition, higher DII impacts overweight/obesity substantially: once the DII score reached Q4, there is still risks of overweight/obesity even if PA is performed.

MiR-204-5p-targeted AP1S2 is necessary for papillary thyroid carcinoma.

MiR-204-5p, as a tumour suppressor, has been found in several cancers. However, whether miR-204-5p is involved in papillary thyroid carcinoma (PTC) has not yet been investigated. In this study, we identified miR-204-5p as a down-regulated miRNA in PTC tissues, unveiling that the levels of miR-204-5p in serum of patients with PTC were linked to PTC risk, and that the expression in patients concomitant with both PTC and benign lesions was much lower than that in patients only with PTC. Furthermore, we documented that miR-204-5p inhibited proliferation, migration, invasion, and cell cycle progression and triggered apoptosis of PTC cells via cell biology experiments. Finally, we identified that AP1S2 was a target of miR-204-5p using RNA-seq, iTRAQ, and bioinformatics prediction. Overall, miR-204-5p functions as a suppressor for PTC pathogenesis via the miR-204-5p/AP1S2 axis.

Transcription factor AP-2 gamma/Krüppel-like factor 10 axis is involved in miR-3656-related dysfunction of endothelial cells in hypertension.

BACKGROUND: Dysfunction of endothelial cells links to microvascular rarefaction, reflecting the pathogenesis of hypertension. Our previous studies found that miR-3656 reduces nitric oxide generation and von Willebrand factor (vWF) cleavage, thereby retarding blood flow and potentially increasing blood pressure. In this paper, we investigated mechanism of transcription regulation contributing to miR-3656-damaged endothelial cells in hypertension. METHODS: The effects of miR-3656 on function of endothelial cells were analyzed on the basis of proliferation, migration, tube formation, and apoptosis. The mRNA level and protein level of genes were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay was performed to confirm the binding between miR-3656 and 3' untranslated region (UTR) of transcription factor AP-2 gamma ( TFAP2C ). The binding between TFAP2C and the promoter region of Krüppel-like factor 10 ( KLF10 ) was confirmed by chromatin immunoprecipitation-qPCR assay. RESULTS: miR-3656 impaired the cell proliferation, migration, tube formation, and apoptosis of endothelial cells. miR-3656 inhibited the expression of TFAP2C by directly targeting 3'UTR of TFAP2C ; moreover, miR-3656-induced injury of endothelial cells was rescued by TFAP2C overexpression. Furthermore, downregulated TFAP2C decreased KLF10 expression by binding to KLF10 promoter region, and upregulated KLF10 reversed the effects of silencing TFAP2C on endothelial cells. These inhibitory processes led to interference of miR-3656 to KLF10-promoted function of endothelial cells. CONCLUSION: TFAP2C/KLF10 axis is involved in miR-3656-related dysfunction of endothelial cells in hypertension. The 3'UTR of TFAP2C and KLF10 promoter region are the hubs of the TFAP2C/KLF10 axis.

C1QA, C1QB, and GZMB are novel prognostic biomarkers of skin cutaneous melanoma relating tumor microenvironment.

Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancers owing to high invasiveness and high metastatic potential. Tumor microenvironment (TME) provides powerful evidences for discerning SKCM, raising the prospect to identify biomarkers of SKCM. Based on the transcriptome profiles of patients with SKCM and the corresponding clinical information from The Cancer Genome Atlas (TCGA), we used ESTIMATE algorithm to calculate ImmuneScore and StromalScore and identified the TME-Related differentially expressed genes (DEGs), than the intersected TME-Related DEGs were used for subsequent functional enrichment analysis. Protein-protein interaction (PPI) analysis was used to identify the functionality-related DEGs and univariate Cox regression analysis was used to identify the survival-related DEGs. Furthermore, SKCM-related DEGs were identified based on two Gene Expression Omnibus (GEO) datasets. Finally, we intersected functionality-related DEGs, survival-related DEGs, and SKCM-related DEGs, ascertaining that six DEGs (CCL4, CXCL10, CCL5, GZMB, C1QA, and C1QB) function as core TME-related genes (CTRGs). Significant differences of GZMB, C1QA, and C1QB expressions were found in gender and clinicopathologic staging of SKCM. High levels of GZMB, C1QA, and C1QB expressions were associated with favorable prognosis. Gene set enrichment analysis (GSEA) showed that cell-cell interaction, cell behavior, and intracellular signaling transduction may be mainly involved in both C1QA, C1QB and GZMB expressions and metabolism of phospholipid and amino acid, transcription, and translation may be implicated in low GZMB expressions. C1QA, C1QB, and GZMB are novel SKCM-relating CTRGs, providing promising immune-related prognostic biomarkers for SKCM.

Association between KCNJ11 E23K polymorphism and the risk of type 2 diabetes mellitus: A global meta-analysis.

BACKGROUND: Potassium inwardly rectifying channel, subfamily J member 11(KCNJ11) is considered to be a potential susceptible gene of type 2 diabetes mellitus (T2DM), and the association between KCNJ11 E23K polymorphism and T2DM risk is still controversial worldwide. This meta-analysis was performed to assess the association more accurately between KCNJ11 E23K polymorphism and T2DM risk. METHODS: The up-to-data meta-analysis was conducted based on studies selected from eight databases (PubMed, Web of Science, Medline, Scopus, Embase, CNKI, WanFang, and Vip). Five gene models were included in our study: allele model (K-allele vs. E-allele), heterozygous model (EK vs. EE), homozygous model (KK vs. EE), dominant genetic model (EK + KK vs. EE), and recessive genetic model (EK + EE vs. KK). Association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI), publication bias was evaluated by Begg's funnel plot and Egger's test, sensitivity analysis and trial sequential analysis (TSA) were used to evaluate the stability of the results. RESULTS: According to the inclusion and exclusion criteria, 31 eligible articles were finally selected in our meta-analysis, including 8754 T2DM cases and 7587 controls. We found that allelic model (OR = 1.25, 95%CI: 1.15-1.35, P < 0.01), heterozygous model (OR = 1.31, 95% CI: 1.18-1.44, P < 0.01), homozygous model (OR = 1.48, 95% CI: 1.24-1.76, P < 0.01), and dominant genetic model (OR = 1.35, 95% CI: 1.22-1.50, P < 0.01) were significantly associated with increased risk of T2DM, but recessive genetic model (OR = 0.78, 95% CI: 0.67-0.91, P < 0.01) was considered as a protective factor for T2DM. No significant evidence of publication bias was found. CONCLUSION: Our meta-analysis confirms the association between KCNJ11 E23K polymorphism and the risk of T2DM, highlighting that gene-gene interaction and gene-environment interaction should be investigated in future.

Meta-analysis of the association between Apolipoprotein E polymorphism and risks of myocardial infarction.

BACKGROUND: Myocardial infarction (MI) remains the leading cause of death and disability among cardiovascular diseases worldwide. Studies show that elevated low-density lipid protein cholesterol (LDL-C) levels confer the highest absolute risk of MI, and Apolipoprotein E (ApoE) is implicated in regulating levels of triglycerides (TGs), cholesterol, and LDL-C. Our study aimed to evaluate the association between APOE polymorphism and MI, and to provide evidence for the etiology of MI. METHODS: Case-control studies on the association between APOE polymorphisms and the risk of myocardial infarction were included by searching PubMed, Web of Science, and CNKI, and this meta-analysis was written in accordance with PRISMA guideline statement. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using either random-effects or fixed-effects models by R software. RESULTS: A total of 33 eligible articles involving 13,706 cases and 14,817 controls were finally selected. The pooled analysis based on the total eligible articles showed that the risk of MI was associated with ApoE epsilon 2 and epsilon 4 alleles. The results showed that patients with MI had a low frequency of the ε2 allele (OR 0.74, 95% CI 0.64-0.86) and a high frequency of the ε4 allele (OR 1.24, 95% CI 1.09-1.42). CONCLUSIONS: APOE ε2-involved genotypes may be protective factors for MI; in contrast, ε4-involved genotypes (ε4/ε3 vs. ε3/ε3, and ε4/ε4 vs. ε3/ε3) may be risk factors for MI.

Epidemiological status quo of hypertension in elderly population in Changchun, China: a cross-sectional study.

OBJECTIVES: To investigate the epidemiological status quo of hypertension in elderly population in Changchun, China, and provide a reference for the prevention and control strategies of hypertension of elderly population in this region. DESIGN: A cross-sectional study, as a part of a comprehensive project in Northeast China, was designed to perform in 10 districts in Changchun. PARTICIPANTS AND SETTING: A total of 6846 participants who were ≥60 years old were selected using a random sampling method. MAIN OUTCOME MEASURES: The epidemiological status quo of hypertension. RESULTS: The prevalence of hypertension in Changchun was 52.6%. Among participants with hypertension enrolled in this study, 87.6% of the participants had been diagnosed with hypertension before the study, 69.1% was taking antihypertensive medications and 66.9% had effective blood pressure control. Obesity, widower/widow, history of diseases and family history of hypertension were risk factors of hypertension (all p<0.05). Participants with obesity, a personal history of heart coronary disease, or a family history of hypertension were susceptible to realising risks of hypertension (all p<0.05). However, participants with diabetes, hyperlipidaemia, or a family history of hypertension were difficult to control blood pressure within the normal range (all p<0.05). In addition, 92.6% participants taking antihypertensive medications used a single medication, and calcium channel blockers was the most commonly used antihypertensive medications in monotherapy. CONCLUSION: The rates of awareness, treatment and control of hypertension are greater in Changchun than those in China, indicating that the prevention and control of hypertension in Changchun are effective. However, the prevalence of hypertension in the elderly population in China is lower than that in Changchun, also rendering Changchun a substantial challenge for the supervision of hypertension.

Sociodemographic and behavioral influences on multimorbidity among adult residents of northeastern China.

BACKGROUND: Multimorbidity is defined as two or more chronic health conditions existing in an individual simultaneously. Multimorbidity has been associated with poor conditions, such as higher health care costs and the poor quality of life. Thus, identifying the risk factors of the multimorbidity is required for multimorbidity prevention. METHODS: This study was based on the Comprehensive Demonstration Research Project of Major Chronic Noncommunicable Disease Prevention and Control Technology in Northeast China initiated by China Medical University. The investigation was a cross-sectional study under a multistage stratified cluster random sampling design. Associations between multimorbidity and sociodemographic and behavioral factors in adult residents were investigated using univariate analysis and multivariate logistic regression analysis. RESULTS: A total of 6706 participants were enrolled in this investigation, and the prevalence of multimorbidity was 21.2% among the adult residents of northeastern China. There existed differences of association between age and multimorbidity risks (65-69 years old: OR = 3.53, 95%CI: 2.04-6.12; 70-74 years old: OR = 5.26, 95%CI: 3.02-9.17). Participants who are overweight had significantly high multimorbidity risk (OR = 2.76, 95%CI: 1.50-5.24). Family history of hypertension and family history of diabetes were significantly associated with high multimorbidity risk (family history of hypertension: OR = 2.34, 95%CI: 1.96-2.79; family history of diabetes: OR = 1.77, 95%CI: 1.38-2.26). Compared with the frequency of fatigue (< 1 time/week or 1-2 times/week), that (≥3 times/week) was associated with high multimorbidity risk (OR = 1.39, 95%CI: 1.07-1.81). For fresh fruit consumption, compared with eating fruits regularly, eating rarely had a higher risk of multimorbidity (OR = 2.33, 95%CI: 1.90-2.85). CONCLUSIONS: Sociodemographic indices (age, BMI, family history of hypertension, and family history of diabetes) and behavioral indices (fatigue status and fresh fruit consumption) increase the risks of multimorbidity. This study provides a necessary route to prevent and control multimorbidity in northeast China.

Circulating miR-3656 induces human umbilical vein endothelial cell injury by targeting eNOS and ADAMTS13: a novel biomarker for hypertension.

BACKGROUND: Hypertension, as one of the most common chronic diseases, is a major public health issue. Previous studies have shown that there are miRNAs differentially expressed in hypertensive patients. In addition, hypertension is closely related to endothelial dysfunction, and miRNAs have been identified as important molecular mediators for endothelial function. Therefore, it is necessary to identify specific miRNAs related to hypertension and explore their molecular mechanism in the progression of hypertension. METHODS: We investigated the association of circulating levels of miR-3656 with hypertension. Furthermore, in-vitro studies were performed to investigate its possible mechanisms for hypertension in that the direct target genes of miR-3656 were confirmed using dual-luciferase reporter assay; moreover, the effects of miR-3656 on proliferation, migration, apoptosis, and microvascular rarefaction of HUVECs were investigated using MTS kit, wound-healing assay, FITC Annexin V apoptosis detection kit, and tube formation assay, correspondingly. RESULTS: Circulating miR-3656 was upregulated in patients with hypertension. MiR-3656 suppressed the proliferation, migration, and angiogenesis of HUVECs, but promoted the apoptosis of HUVECs. In addition, eNOS and ADAMTS13 were direct target genes of miR-3656, and overexpression of eNOS and ADAMTS13 abolished the effect of miR-3656 on HUVECs. CONCLUSION: MiR-3656 is a potential biomarker for hypertension. MiR-3656 is involved in endothelial cellular injury implicated in hypertension by targeting eNOS and ADAMTS13.

Poor Uncorrected Visual Acuity and Association With Sleep Duration and Screen Time: A Dose-Response Relationship Study.

BACKGROUND: We aimed to investigate the prevalence of poor uncorrected visual acuity and the difference among students with different ages and residential areas in the Northeast of China. The relationships between screen time, nighttime sleep duration, and poor uncorrected visual acuity would be explored. METHODS: It was a cross-sectional study using multi-stage stratified random sampling method to recruit participants. 2149 students have completed questionnaires and underwent visual acuity examinations. The dose-response curve method was applied to examine the non-linear associations between sleep duration and poor uncorrected visual acuity under different screen time subgroups. RESULTS: The overall prevalence of poor uncorrected visual acuity and severe poor uncorrected visual acuity was 84.7% and 63.3%, respectively. The dose-response curve showed the odds ratios (ORs) of sleep duration for the poor uncorrected visual increased relatively slowly when screen time <1 hour, then increased dramatically in screen time ≥1 hours. The ORs of sleep time and poor uncorrected visual acuity showed a U-shaped change trend among students with 2 or more hours of screen time every day. CONCLUSION: We found associations between nighttime sleep duration and poor uncorrected visual acuity in adolescents. However, these associations were not consistent across all screen time categories.

Association between eNOS rs1799983 polymorphism and hypertension: a meta-analysis involving 14,185 cases and 13,407 controls.

BACKGROUND: Essential hypertension is a complex disease determined by the interaction of genetic and environmental factors, eNOS is considered to be one of the susceptible genes for hypertension. Our study aimed to evaluate the association between eNOS rs1799983 polymorphism and hypertension, and to provide evidence for the etiology of hypertension. METHODS: Case-control studies of eNOS rs1799983 polymorphism and hypertension were included by searching PubMed, Embase, Web of Science, Medline, Scopus, WanFang datebase, Vip datebase, and CNKI database according to PRISMA guideline. Eligible data were extracted and pooled, and were analyzed using R software based on five different genetic models. RESULTS: A total of 60 eligible articles involving 14,185 cases and 13,407 controls were finally selected. We found significant association between eNOS rs1799983 polymorphism and hypertension under any genetic model (T vs G: OR = 1.44, 95% CI 1.26-1.63; GT vs GG: OR 1.34, 95% CI 1.18-1.52; TT vs GG: OR 1.80, 95% CI 1.41-2.31; GT + TT vs GG: OR 1.42, 95% CI 1.25-1.63; TT vs GG + GT: OR 1.68, 95% CI 1.35-2.08; GT vs GG + TT: OR 1.24, 95% CI 1.11-1.40). CONCLUSIONS: We found that eNOS rs1799983 polymorphism is associated with the increased risk of hypertension under any genetic model. Moreover, investigations of gene-gene and gene-environment interactions are needed to give more insight into the association between eNOS rs1799983 polymorphism and hypertension.

Down-regulated FST expression is involved in the poor prognosis of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is more commonly associated with young patients, featuring high histological grade, visceral metastasis, and distant recurrence. Follistatin (FST) is a secreted extracellular regulatory protein that antagonizes TGF-ß superfamily such as activin and TGF-ß related superfamily such as bone morphogenetic protein (BMP). The implication of FST in the proliferation, angiogenesis, and metastasis of solid tumors documents good or poor outcome of patients with BC. However, the role of FST in TNBC remains unclear. METHODS: Data of 935 patients with breast cancer (BC) were extracted from TCGA. Case-control study, Kaplan-Meier, uni-multivariate COX, and ROC curve were utilized to investigate the relationship between FST expression and the clinical characteristics and prognosis of BC. Functional studies were used to analyze the effect of FST expression on proliferation, apoptosis, migration, and invasion of TNBC cell lines. Bioinformatic methods such as volcanoplot, GO annd KEGG enrichment, and protein-protein interactions (PPI) analyses were conducted to further confirm the different roles of FST in the apoptotic pathways among mesenchymal and mesenchymal stem-like cells of TNBC. RESULTS: Data from TCGA showed that low FST expression correlated with poor prognosis (for univariate analysis, HR = 0.47, 95% CI: 0.27-0.82, p = 0.008; for multivariate analysis, HR = 0.40, 95% CI: 0.21-0.75, p = 0.004). Low FST expression provided high predicted value of poor prognosis in TNBC amongst BCs. FST knockdown promoted the proliferation, migration and invasion of BT549 and HS578T cell lines. FST inhibited the apoptosis of mesenchymal cells by targeting BMP7. CONCLUSIONS: Low FST expression is associated with poor prognosis of patients with TNBC. FST expressions exhibit the anisotropic roles of apoptosis between mesenchymal and mesenchymal stem-like cells but promote the proliferation, migration, invasion in both of two subtypes of TNBC in vitro. FST may be a subtype-heterogeneous biomarker for monitoring the progress of TNBC.

OLFML2A is necessary for anti-triple negative breast cancer effect of selective activator protein-1 inhibitor T-5224.

Previous studies have shown that expression of activator protein-1 (AP-1) family is significantly elevated in triple-negative breast cancer (TNBC), compared with that in other breast cancer subtypes. Here we investigated the anti-tumor effect and mechanism of T-5224, an inhibitor of c-Fos/AP-1, on TNBC. We identified that T-5224 inhibited the proliferation, migration, and invasion of TNBC cells and resulted in an increase in apoptosis. Furthermore, we found that OLFML2A is a key regulatory protein acting downstream of AP-1 and is involved in T-5224-targeted AP-1 action. Multiple clinical databases online have identified that high OLFML2A level is associated with poor prognosis in TNBC patients. In summary, our experimental and bioinformatic studies indicated that OLFML2A is necessary for AP-1-overexpressing TNBC. These findings demonstrate that AP-1-overexpressing TNBC dependent on OLFML2A, and targeting both AP-1 and OLFML2A through T-5224 may be a synergistic therapeutic strategy for this clinically challenging subset of breast cancer.

Circulating miR-3135b and miR-107 are potential biomarkers for severe hypertension.

Hypertension is a disease relating to multiple etiological factors. However, the molecular mechanisms of severe hypertension remain unclear. Whole-body circulatory dysregulation has been found to contribute to hypertension, documenting that circulating molecules are focused as pathological molecules implicated in hypertension. Circulating microRNAs (miRNAs) have been identified as important molecular biomarkers for hypertension. We screened and analyzed miRNAs differentially expressed in plasma in patients with severe hypertension and healthy controls using microarray profiling (six patients and six healthy controls for screening) and RT-qPCR (33 patients and 33 healthy controls for validation). We identified that miR-3135b and miR-107 are the differentially expressed miRNAs between severe hypertension and healthy controls, and the target genes independently regulated by the two miRNAs are remarkably different. MiR-3135b and miR-107 are potential biomarkers for severe hypertension.

Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is becoming increasingly prevalent of late. Methylenetetrahydrofolate reductase (MTHFR) has a significant role in folate metabolism. Owing to the inconsistencies and inconclusiveness on the association between MTHFR single nucleotide polymorphism (SNP) and ASD susceptibilities, a meta-analysis was conducted to settle the inconsistencies. METHODS: For this meta-analysis, a total of 15 manuscripts published up to January 26, 2020, were selected from PubMed, Google Scholar, Medline, WangFang, and CNKI databases using search terms "MTHFR" OR "methylenetetrahydrofolate reductase" AND "ASD" OR "Autism Spectrum Disorders" OR "Autism" AND "polymorphism" OR "susceptibility" OR "C677T" OR "A1298C". RESULTS: The findings of the meta-analysis indicated that MTHFR C677T polymorphism is remarkably associated with ASD in the five genetic models, viz., allelic, dominant, recessive, heterozygote, and homozygote. However, the MTHFR A1298C polymorphism was not found to be significantly related to ASD in the five genetic models. Subgroup analyses revealed significant associations of ASD with the MTHFR (C677T and A1298C) polymorphism. Sensitivity analysis showed that this meta-analysis was stable and reliable. No publication bias was identified in the associations between MTHFRC677T polymorphisms and ASD in the five genetic models, except for the one with regard to the associations between MTHFRA1298C polymorphisms and ASD in the five genetic models. CONCLUSION: This meta-analysis showed that MTHFR C677T polymorphism is a susceptibility factor for ASD, and MTHFR A1298C polymorphism is not associated with ASD susceptibility.

ε2 allele and ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: a meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive. METHODS: An up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database. RESULTS: A total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ε2 vs. ε3 was 1.89 (95% confidence intervals [95% CI]: 1.49-2.38, P < 0.0001). With regard to APOE genotypes, ε2/ε2, ε2/ε3, and ε2/ε4 increased the risk of T2DN (ε2/ε2 vs. ε3/ε3: OR = 2.32, 95% CI: 1.52-3.56, P = 0.0001; ε2/ε3 vs. ε3/ε3: OR = 1.97, 95% CI: 1.50-2.59, P<0.0001; ε2/ε4 vs. ε3/ε3: OR = 1.69, 95% CI: 1.18-2.44, P = 0.0046). CONCLUSIONS: This meta-analysis found that the APOE ε2 allele and the ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) are the risk factors of T2DN.

Prevalence of autism spectrum disorder in Asia: A systematic review and meta-analysis.

There has been an increased prevalence of the diagnosis of Autism Spectrum Disorder (ASD) globally during the last decade. An updated and overall estimate of ASD prevalence in Asia would assist health professionals to develop relevant public health strategies. We performed a systematic review by searching English databases (Medline, Embase, Web of Science, and Cochran Library) from inception date to August 6, 2018. Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Publication bias was evaluated using Egger's test. A total of 2,195,497 subjects in Asia from 12 eligible studies were included in this meta-analysis. The pooled estimate of ASD prevalence among the included subjects was 0.36% (95% CI: 0.16-0.79%). The pooled ASD prevalence in males (0.45%, 95% CI: 0.19-1.04%) was higher than that in females (0.18%, 95% CI: 0.079-0.49%). ASD prevalence in East Asia, South Asia, and West Asia was 0.51% (95% CI: 0.06-4.22%), 0.31% (95% CI: 0.14-0.65%), and 0.35% (95% CI: 0.07-1.80%) respectively. The prevalence of ASD is increasing in Asia. Universal and standardized diagnostic processes for ASD should be adopted for the prevention and control programs of ASD in future.

SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age.

Autism spectrum disorder (ASD) is a serious lifelong neurodevelopmental disorder. ASD is diagnosed for children at the age of two. ASD diagnosis, as early as possible, lays the foundation for treatment and much better prognosis. Notably, gene-based test is an inherent method to recognize the potential infants with ASD before the age of two. To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. We enrolled 470 subjects (229 cases and 241 healthy controls) who were northeast Chinese Han. Four tag SNPs (rs73042561, rs3745521, rs4801846, and rs12461427) of SHANK1 were selected and genotyped. We used the SNPStats online analysis program to assess the associations between the four SNPs and ASD risk. The SNP-SNP interactions among SHANK family were analyzed using multifactor dimensionality reduction method. We found that the four SHANK1 SNPs were not associated with ASD risk in northeast Chinese Han population. There existed a strong synergistic interaction between rs11236697 [SHANK2] and rs74336682 [SHANK2], and moderate synergistic interactions (rs74336682 [SHANK2]-rs73042561 [SHANK1], rs11236697 [SHANK2]-rs77716438 [SHANK2], and rs11236697 [SHANK2]-rs75357229 [SHANK2]). These SHANK1 variants may not affect the susceptibility to ASD in Chinese Han population. SNP-SNP interactions in SHANK family may confer ASD risk. Autism Res 2019, 12: 375-383 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a serious lifelong neurodevelopmental disorder with strong genetic components. We investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. Our results indicated that there exists no association between SHANK1 SNPs and ASD, and SNP-SNP interactions in SHANK family may confer ASD risk in the Northeast Han Chinese population. Future studies are needed to test more SHANK family SNPs in a large sample to demonstrate the associations.