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To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend <0.001). Compared with quartile 1, the multivariate-adjusted hazard ratios (HRs) and its 95% confidence intervals (95% CIs) for T2DM risk were 1.16 (0.97-1.38) for quartile 2, 1.28 (1.07-1.51) for quartile 3, and 1.28 (1.08-1.52) for quartile 4 (p trend = 0.005). HR for per each standard deviation increase in BUN level was 1.10 (1.04-1.16) (p trend <0.001). This association tended to be more pronounced in those with a lower body mass index at baseline (p-interaction <0.001). Our results suggested that BUN levels were positively associated with incident T2DM risk among Chinese adults. Future prospective investigations in other populations are necessary to confirm our findings.
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Nitrogênio da Ureia Sanguínea , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Povo Asiático/estatística & dados numéricos , Glicemia/análise , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case-control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
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Cálcio da Dieta/administração & dosagem , Laticínios , Dieta , Neoplasias Ovarianas/epidemiologia , Vitamina D/administração & dosagem , Animais , Cálcio/sangue , Estudos de Casos e Controles , Estudos de Coortes , Laticínios/efeitos adversos , Dieta/efeitos adversos , Feminino , Humanos , Leite/química , Risco , Vitamina D/sangueRESUMO
BACKGROUND: Patients suffering from acute kidney injury (AKI) were associated with impaired sodium and potassium homeostasis. We aimed to investigate how admission serum sodium and potassium independently and jointly modified adverse clinical outcomes among AKI patients. METHODS: Patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III. Participants were categorized into three groups according to admission serum sodium and potassium, and the cut-off values were determined using smooth curve fitting. The primary outcome was 90-day mortality in the intensive care unit (ICU). Cox proportional hazards models were used to evaluate the prognostic effects of admission serum sodium and potassium levels. RESULTS: We included 13,621 ICU patients with AKI (mean age: 65.3 years; males: 55.4%). The middle category of admission serum sodium and potassium levels were 136.0-144.9 mmol/L and 3.7-4.7 mmol/L through fitting smooth curve. In multivariable Cox models, compared with the middle category, patients with hyponatremia or hypernatremia were associated with excess mortality and the HRs and its 95%CIs were 1.38 (1.27, 1.50) and 1.56 (1.36, 1.79), and patients with either hypokalemia or hyperkalemia were associated with excess mortality and the hazard ratios (HRs) and its 95% confidential intervals (95% CIs) were 1.12 (1.02, 1.24) and 1.25 (1.14, 1.36), respectively. Significant interactions were observed between admission serum sodium and potassium levels (P interaction = 0.001), with a higher serum potassium level associated with increased risk of 90-day mortality among patients with hyponatremia, whereas the effects of higher sodium level on prognostic effects of potassium were subtle. CONCLUSIONS: Admission serum sodium and potassium were associated with survival in a U-shaped pattern among patients with AKI, and hyperkalemia predict a worse clinical outcome among patients with hyponatremia.
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Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Mortalidade Hospitalar , Potássio/sangue , Sódio/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Intervalos de Confiança , Creatinina/sangue , Estado Terminal/mortalidade , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Hiperpotassemia/mortalidade , Hipernatremia/mortalidade , Hipopotassemia/mortalidade , Hiponatremia/mortalidade , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Fatores Sexuais , Estatísticas não ParamétricasRESUMO
[This corrects the article DOI: 10.3389/fendo.2022.880683.].
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The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) (P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (pinteraction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.
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Calcinose , Calcificação Vascular , Humanos , Estudos de Coortes , Periodontite , China , Radiografia Torácica , Aorta Torácica/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Calcinose/etiologiaRESUMO
Objectives: Non-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis. Methods: This prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort. Results: Of the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0-55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02-1.38) and 1.18 (1.01-1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes. Conclusions: NAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Adulto , Colesterol , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Humanos , Lipídeos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pontuação de Propensão , Estudos ProspectivosRESUMO
This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.
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COVID-19/epidemiologia , Exercício Físico/psicologia , Tempo de Tela , Privação do Sono/epidemiologia , Estudantes/psicologia , Adolescente , COVID-19/psicologia , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Inquéritos e QuestionáriosRESUMO
AIMS/INTRODUCTION: The current literature suggests that men with diabetes have a lower prostate-specific antigen concentration than men without diabetes, but the causal association remains unclear. We aimed to investigate the association between serum prostate-specific antigen concentrations and the risk of type 2 diabetes mellitus in a cohort study of a Chinese population. MATERIALS AND METHODS: We designed a cohort study that comprised 16,811 initially non-diabetic Chinese men who received annual health checkups between 2009 and 2016. The outcome of this study was type 2 diabetes mellitus, identified by medical diagnosis, self-reportage, medication use, fasting glucose, 2-h post oral glucose or glycated hemoglobin measurements. Cox proportional hazards models were carried out to evaluate the association. RESULTS: During a median follow-up period of 3.8 years (interquartile range 1.91-5.73 years), 1,260 participants developed incident type 2 diabetes mellitus. The multivariable model, adjusted for various potential confounders, showed that serum prostate-specific antigen concentrations were inversely related to type 2 diabetes mellitus risk (P for trend = 0.014). Compared with the lowest quartile of serum prostate-specific antigen, the hazard ratio and 95% confidence intervals of type 2 diabetes mellitus risk for quartile 2-4 were 0.84 (0.66-1.07), 0.75 (0.59-0.94) and 0.77 (0.62-0.96), respectively. Subgroup analyses suggested the inverse relationship was more prominent in overweight or obese participants (P for interaction = 0.013). CONCLUSIONS: High serum prostate-specific antigen concentration was associated with a low risk of type 2 diabetes mellitus in Chinese men. Future studies are required to confirm these findings and investigate underlying mechanisms.
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Biomarcadores/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/epidemiologia , Antígeno Prostático Específico/sangue , Adulto , Idoso , China/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To explore the value of color Doppler ultrasound in evaluating the therapeutic effects on ankylosing spondylitis (AS) patients. METHODS: Color Doppler high-frequency ultrasound images and blood flow in 30 healthy volunteers and 50 AS patients, changes of high-frequency ultrasound images and blood flow of involved sites in AS patients pre- and after-Etanercept treatments, as well as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity indices pre- and post-treatment were compared. RESULTS: Positive rates were significantly different between healthy volunteers and AS patients in terms of sacroiliac joints, Achilles tendon attachments, patellar ligament attachments, and rectus femoris tendon attachments by ultrasonograph (P < 0.05); and the fibular collateral ligament attachments positive rates had no significant difference with those at pre-treatment (P > 0.05). There was significant difference between patients with Bath AS disease activity index (BASDAI) ≥ 4 and those with BASDAI < 4 with respects to peripheral enthesis positive rate, Bath AS functional index (BASFI), patient's global assessment VAS (PGA), nocturnal back pain and general back pain VAS, morning stiffness duration, ESR and CRP (P < 0.05). Positive rates of sacroiliac joints, Achilles tendon attachments, patellar ligament attachments and rectus femoris tendon by ultrasonograph significantly decreased at Weeks 12 and 24 at post-treatment compared to that at pre-treatment (P < 0.05); there was significant difference for patient's BASDAI, BASFI, ESR and CRP at pre-treatment and weeks 12 and 24 post-treatment (P < 0.05). CONCLUSION: Ultrasound can sensitively detect the pathological changes of joint synovium and entheses so that it may be used as a routine method of monitoring diseases in these soft tissues, following up AS patients and evaluating clinical efficacy.
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Doenças Reumáticas/terapia , Sacroileíte/terapia , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/terapia , Ultrassonografia Doppler em Cores , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tendões/diagnóstico por imagem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Previous studies have examined the role of the KQT-like subfamily Q member1 (KCNQ1) gene polymorphisms on the risk of type 2 diabetes mellitus (T2DM), but the findings are inconclusive. OBJECTIVE: To examine the association between the KCNQ1 gene polymorphisms and the risk of T2DM using an updated meta-analysis with an almost tripled number of studies. METHODS: Five electronic databases, such as PubMed and Embase, were searched thoroughly for relevant studies on the associations between seven most studied KCNQ1 gene polymorphisms, including rs2237892, rs2237897, rs2237895, rs2283228, rs231362, rs151290, and rs2074196, and T2DM risk up to September 14, 2019. The summary odds ratios (ORs) with their 95% confidence intervals (CIs) were applied to assess the strength of associations in the random-effects models. We used the trial sequential analysis (TSA) to measure the robustness of the evidence. RESULTS: 49 publications including 55 case-control studies (68,378 cases and 66,673 controls) were finally enrolled. In overall analyses, generally, increased T2DM risk was detected for rs2237892, rs2237895, rs2283228, rs151290, and rs2074196, but not for rs231362 under all genetic models. The ORs and 95% CIs for allelic comparison were 1.23 (1.14-1.33) for rs2237892, 1.21 (1.16-1.27) for rs2237895, 1.27 (1.11-1.46) for rs2237897, 1.25 (1.09-1.42) for rs2283228, 1.14 (1.03-1.27) for rs151290, 1.31 (1.23-1.39) for rs2074196, and 1.16 (0.83, 1.61) for rs231362. Stratified analyses showed that associations for rs2237892, rs2237895, rs2283228, and rs151290 were more evident among Asians than Caucasians. TSA demonstrated that the evidence was sufficient for all polymorphisms in this study. The genotypes of the three SNPs (rs2237892, rs2283228, and rs231362) were significantly correlated with altered KCNQ1 gene expression. CONCLUSION: This meta-analysis suggested that KCNQ1 gene polymorphisms (rs2237892, rs2283228, rs2237895, rs151290, and rs2074196) might be the susceptible factors for T2DM, especially among Asian population.
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Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Canal de Potássio KCNQ1/genética , Polimorfismo de Nucleotídeo Único , Alelos , Frequência do Gene , Estudos de Associação Genética , Genótipo , HumanosRESUMO
INTRODUCTION: Brachial-ankle pulse wave velocity (ba-PWV), as a simple and easily measured marker of arterial stiffness, has not been prospectively explored for its role in type 2 diabetes mellitus (T2DM) risk among the general population. This study aimed to explore the association between baseline ba-PWV value and new-onset T2DM among Chinese adults. RESEARCH DESIGN AND METHODS: Using data from Xiaotangshan Hospital, we conducted a prospective cohort study among those who underwent annual or biennial health check-up examinations and who had their ba-PWV measured from 2009 to 2016. We explored the risk of new-onset T2DM across ba-PWV tertiles using Cox proportional-hazards regression analysis. RESULTS: Of 6122 adults (68.9% male; mean age: 51.0 (SD 13.0) years) without T2DM and with ba-PWV measured at baseline, 599 participants developed T2DM during an average of 3.8 (SD 2.3) years of follow-up. After multivariable adjustment, ba-PWV was positively related to T2DM risk (p for trend=0.008). Compared with the lowest ba-PWV tertile, the HRs and their 95% CIs were 1.57 (1.18 to 2.10) for the second and 1.66 (1.24 to 2.22) for the third tertile. The risk across ba-PWV tertiles increased steadily from 1000 cm/s to 1400 cm/s and then reached a plateau. Subgroup analyses indicated a significantly higher risk among those aged <65 years and current smokers (p for interactions: <0.001 and 0.006). CONCLUSIONS: Our findings suggest that ba-PWV might be a useful and independent predictor of new-onset T2DM with ba-PWV ranging between 1000 cm/s and 1400 cm/s, especially among younger individuals and current smokers.
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Índice Tornozelo-Braço , Diabetes Mellitus Tipo 2 , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Fatores de RiscoRESUMO
INTRODUCTION: In this meta-analysis, we analyzed retrospective cohort studies that assessed the prognostic potential of the pretreatment lymphocyte-to-monocyte ratio (LMR) among patients with ovarian cancer (OC). MATERIALS AND METHODS: We comprehensively searched electronic databases, including PubMed and Embase, from inception through October 2018. A random-effects model was used to calculate pooled HRs and their 95% CIs for overall survival (OS) and progression-free survival (PFS). The low LMR group was treated as the reference group. RESULTS: Twelve studies, including 3,346 OC cases at baseline, were included. Overall, our results indicated that LMR was positively associated with both OS (HR: 1.85, 95% CI: 1.50-2.28, P<0.001; I 2=76.5%) and PFS (HR: 1.70, 95% CI: 1.49-1.94, P<0.001; I 2=24.4%) among OC patients. Stratified analyses indicated that, for OS, the LMR's protective effect was more evident in studies conducted among younger patients (<55 years) than in those conducted among older patients (≥55 years; P for interaction =0.017), which was confirmed by meta-regression analysis (P=0.004). CONCLUSION: This study suggested that a higher pretreatment LMR level was associated with a favorable prognosis among OC patients. Future large-scale prospective clinical trials are needed to confirm the prognostic value of LMR among OC patients.
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OBJECTIVE: There has been growing body of literatures showing that chronic inflammation might play an important role in cancer development. This meta-analysis aimed to assess the association between the dietary inflammation index (DII) score and gynecological cancers. METHODS: A systematic search of PubMed, EMBASE and Web of Science up until October 20, 2018 was carried out to retrieve all related cohort and case-control studies. The summary risk assessments were pooled using random-effects models. The dose-response relationship was estimated by linear relationship model. RESULTS: Twelve case-control studies (10,774 cases/15,958 controls) and six prospective cohort studies (330,363 participants/23,133 incident cases) were included in this meta-analysis. The pooled adjusted relative risk (RR) of gynecological cancers for the highest DII category compared to the lowest category was 1.38, (95% confidence intervals [CIs], 1.21-1.56, p<0.001]. A positive dose-response relationship was also noticed. Stratified by study design indicated that, the pooled RRs was significantly higher for case-control studies than cohort studies (p for interaction<0.001), for studies conducted among participants with body mass index (BMI) ≥25 kg/m² than participants with BMI <25 kg/m² (p for interaction=0.026), among participants with ovarian cancer and endometrial cancer than participants with breast cancer (p for interaction = 0.038). Meta-regression analysis further confirmed that study design significantly contributed to inter-study heterogeneity (p<0.001). CONCLUSION: This meta-analysis suggests that elevated DII is independently associated with a higher risk of gynecological cancers, especially patients with ovarian cancer and endometrial cancer and among obese participants.
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Dieta/efeitos adversos , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/etiologia , Inflamação/epidemiologia , Inflamação/etiologia , Estudos Observacionais como Assunto/estatística & dados numéricos , Estudos de Casos e Controles , China/epidemiologia , Doença Crônica , Estudos de Coortes , Feminino , Indicadores Básicos de Saúde , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Previous studies have examined the roles of three polymorphisms (rs3851179, rs541458, and rs592297) of the PICALM gene in susceptibility to Alzheimer's disease (AD) with inconclusive findings. OBJECTIVE: We performed a meta-analysis to explore whether these three polymorphisms in the PICALM gene were associated with susceptibility to AD. METHODS: Bibliographical searches were conducted in the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. Summary Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were used to assess the strength of association in a random effects model. Potential sources of heterogeneity were identified by subgroup and meta-regression analyses. RESULTS: Twenty studies (9,017 cases and 15,448 controls) on rs3851179, 12 studies (8,077 cases and 12,022 controls) on rs541458, and 4 studies (2,106 cases and 2,234 controls) on rs592297 were considered eligible for meta-analyses. For both rs3851179 and rs541458, the overall ORs were significant under all genetic models with mild heterogeneity. Compared with G carriers, A carriers of rs3851179 were associated with a decreased risk of AD (OR = 0.88; 95% CI 0.84, 0.91, P for Z-test <0.001, I2 = 0.0%). Compared with T carriers, C carriers of rs541458 were inversely associated with AD risk (OR = 0.86; 95% CI 0.81, 0.92, P for Z-test <0.001, I2 = 39.5%). No association was observed for rs592297. Subgroup and meta-regression analyses indicated that the protective effect of the rs541458 C allele was observed only among Caucasians, not among Asians (P for interaction: 0.021~<0.001). CONCLUSION: rs3851179 and rs541458 appear to be associated with decreased AD risk. The null associations for rs592297 with AD risk need further confirmation with a larger number of participants.