Comprehensive assessment of protein loop modeling programs on large-scale datasets: prediction accuracy and efficiency.

Protein loops play a critical role in the dynamics of proteins and are essential for numerous biological functions, and various computational approaches to loop modeling have been proposed over the past decades. However, a comprehensive understanding of the strengths and weaknesses of each method is lacking. In this work, we constructed two high-quality datasets (i.e. the General dataset and the CASP dataset) and systematically evaluated the accuracy and efficiency of 13 commonly used loop modeling approaches from the perspective of loop lengths, protein classes and residue types. The results indicate that the knowledge-based method FREAD generally outperforms the other tested programs in most cases, but encountered challenges when predicting loops longer than 15 and 30 residues on the CASP and General datasets, respectively. The ab initio method Rosetta NGK demonstrated exceptional modeling accuracy for short loops with four to eight residues and achieved the highest success rate on the CASP dataset. The well-known AlphaFold2 and RoseTTAFold require more resources for better performance, but they exhibit promise for predicting loops longer than 16 and 30 residues in the CASP and General datasets. These observations can provide valuable insights for selecting suitable methods for specific loop modeling tasks and contribute to future advancements in the field.

Fast drug rotation reduces bacterial resistance evolution in a microcosm experiment.

Drug rotation (cycling), in which multiple drugs are administrated alternatively, has the potential for limiting resistance evolution in pathogens. The frequency of drug alternation could be a major factor to determine the effectiveness of drug rotation. Drug rotation practices often have low frequency of drug alternation, with an expectation of resistance reversion. Here we, based on evolutionary rescue and compensatory evolution theories, suggest that fast drug rotation can limit resistance evolution in the first place. This is because fast drug rotation would give little time for the evolutionarily rescued populations to recover in population size and genetic diversity, and thus decrease the chance of future evolutionary rescue under alternate environmental stresses. We experimentally tested this hypothesis using the bacterium Pseudomonas fluorescens and two antibiotics (chloramphenicol and rifampin). Increasing drug rotation frequency reduced the chance of evolutionary rescue, and most of the finally surviving bacterial populations were resistant to both drugs. Drug resistance incurred significant fitness costs, which did not differ among the drug treatment histories. A link between population sizes during the early stages of drug treatment and the end-point fates of populations (extinction vs survival) suggested that population size recovery and compensatory evolution before drug shift increase the chance of population survival. Our results therefore advocate fast drug rotation as a promising approach to reduce bacterial resistance evolution, which in particular could be a substitute for drug combination when the latter has safety risks.

Sugar-sweetened beverages and risk of hypertension and CVD: a dose-response meta-analysis.

A number of prospective cohort studies have investigated the associations between consumption of sugar-sweetened beverages (SSB) and the risk of hypertension, CHD and stroke, but revealed mixed results. In the present study, we aimed to perform a dose-response meta-analysis of these prospective studies to clarify these associations. A systematic literature search was conducted using the PubMed and Embase databases up to 5 May 2014. Random- or fixed-effects models were used to calculate the pooled relative risks (RR) with 95 % CI for the highest compared with the lowest category of SSB consumption, and to conduct a dose-response analysis. A total of six prospective studies (240 726 participants and 80 411 incident cases of hypertension) from four publications on hypertension were identified. A total of four prospective studies (194 664 participants and 7396 incident cases of CHD) from four publications on CHD were identified. A total of four prospective studies (259 176 participants and 10 011 incident cases of stroke) from four publications on stroke were identified. The summary RR for incident hypertension was 1·08 (95 % CI 1·04, 1·12) for every additional one serving/d increase in SSB consumption. The summary RR for incident CHD was 1·17 (95 % CI 1·10, 1·24) for every serving/d increase in SSB consumption. There was no significant association between SSB consumption and total stroke (summary RR 1·06, 95 % CI 0·97, 1·15) for every serving/d increase in SSB consumption. The present meta-analysis suggested that a higher consumption of SSB was associated with a higher risk of hypertension and CHD, but not with a higher risk of stroke.

Associations of genetic variants in/near body mass index-associated genes with type 2 diabetes: a systematic meta-analysis.

OBJECTIVE: Genome-wide association studies have identified many obesity/body mass index (BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/BMI loci with T2D risk and explore how BMI influences this risk. METHODS: We retrieved published literature from PubMed and Embase. The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed- or random-effect models. RESULTS: In the meta-analysis of 42 studies for 11 obesity/BMI-associated loci, we observed a statistically significant association of the FTO rs9939609 polymorphism (66 425 T2D cases/239 689 normoglycaemic subjects; P = 1·00 × 10(-41) ) and six other variants with T2D risk (17 915 T2D cases/27 531 normoglycaemic individuals: n = 40 629-130 001; all P < 0·001 for SH2B1 rs7498665, FAIM2 rs7138803, TMEM18 rs7561317, GNPDA2 rs10938397, BDNF rs925946 and NEGR1 rs2568958). After adjustment for BMI, the association remained statistically significant for four of the seven variants (all P < 0·05 for FTO rs9939609, SH2B1 rs7498665, FAIM2 rs7138803, GNPDA2 rs10938397). Subgroup analysis by ethnicity demonstrated similar results. CONCLUSIONS: This meta-analysis indicates that several BMI-associated variants are significantly associated with T2D risk. Some variants increase the T2D risk independent of obesity, while others mediate this risk through obesity.

Loss and recovery of ecological diversity associated with evolutionary rescue in abruptly and gradually deteriorating environments.

Populations may survive environmental deterioration by evolutionary adaptation. However, such evolutionary rescue events may be associated with ecological costs, such as reduction in growth performance and loss of ecologically important genetic diversity. Those negative ecological consequences may be mitigated by additional adaptive evolution. Both the ecological costs and the opportunities for additional evolution are contingent on the severity of environmental deterioration. Here, we hypothesize that populations evolutionarily rescued from faster, relative to slow, environmental deterioration suffer more severe long-term fitness decline and diversity loss. An experiment with the model adaptive radiation of bacterium Pseudomonas fluorescens exposed to abruptly or gradually increased antibiotic stress supported our hypothesis. The effect of additional adaptive evolution in recovering population size and ecological diversity was far from perfect. Cautions are therefore needed in predicting the role of rapid evolution for mitigating the impacts of environmental changes, in particular very fast environmental deterioration. We also found that bacterial populations rescued from gradually increased antibiotic stress evolved higher levels of antibiotic resistance, lending more support to aggressive chemotherapy in pathogen control.

Prevalence of metabolic syndrome and its influencing factors among the Chinese adults: the China Health and Nutrition Survey in 2009.

OBJECTIVE: We aimed to estimate the up-to-date prevalence of metabolic syndrome (MS) and its influencing factors among the Chinese adults. METHODS: Data were obtained from the China Health and Nutrition Survey conducted in 2009, which was a cross-sectional and partially nationally representative study including a total of 7488 Chinese adults (age ≥18 years). RESULTS: The overall age-standardized prevalence estimates of the MS were 21.3% (95%confidence interval (CI): 20.4%-22.2%), 18.2% (95%CI: 17.3%-19.1%) and 10.5% (95%CI: 9.8%-11.2%) based on definitions of revised NCEP ATPIII, IDF and CDS criteria, respectively. Individuals who were women (compared to men: odds ratio [OR]=1.37, 95% CI=1.16-1.61), 40 years or older (compared to less than 40 years old: OR=2.82, 95%CI=2.37-3.34 for 40-59 years; OR=4.41, 95%CI=3.68-5.29 for 60 years or older), overweight/obese (compared to normal weight: OR=4.32, 95%CI=3.77-4.95 for overweight; OR=11.24, 95%CI=9.53-13.26 for obese), and living in urban area (compared to living in rural area: OR=1.27, 95%CI=1.12-1.43) were more likely to have a higher prevalence estimate of MS. In addition, frequency of alcohol consumption and cigarette intake were also found to be significantly associated with probability of MS. CONCLUSIONS: Our results suggest an urgent need to develop national strategies for the prevention, detection, treatment and control of obesity and MS in China.

Common variant (rs9939609) in the FTO gene is associated with metabolic syndrome.

Recent genome-wide association studies have showed that common variant (rs9939609) in fat mass and obesity associated (FTO) gene was significantly associated with type 2 diabetes through an effect on human body mass index/obesity. Further studies have suggested that this variant was also involved in the development of metabolic syndrome (MetS). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association between rs9939609 polymorphism and the risk of MetS. Published literature from PubMed, EMBASE and other databases were searched. All studies assessing the association between rs9939609 polymorphism and the risk of MetS were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed-effects model. Thirteen studies (8,370 cases and 23,156 controls) using NCEP ATPIII criteria for MetS were pooled with a meta-analysis. The overall result showed that there was a statistically significant association between rs9939609 polymorphism and MetS risk (OR = 1.11, 95% CI = 1.06-1.17). Subgroup analysis based on ethnicity showed that effect size was only statistically significant in Europeans (OR = 1.11, 95% CI = 1.05-1.16). Eight studies (1,256 cases and 2,551 controls) using IDF criteria for MetS were pooled with a meta-analysis. The overall analysis suggested that rs9939609 polymorphism was significantly associated with MetS risk (OR = 1.32, 95% CI = 1.13-1.54). Subgroup analysis stratified by ethnicity suggested that effect size was only statistically significant in Asians (OR = 1.33, 95% CI = 1.10-1.61). Our results suggested that FTO rs9939609 polymorphism was significantly associated with the increased risk of MetS in European and Asian populations. Mechanistic investigation is also needed to clarify the effect of FTO gene in the predisposition to MetS.

Effects of 25-hydroxy vitamin D on T lymphocyte subsets and sputum smear conversion during antituberculosis treatment.

OBJECTIVES: This study aimed to explore the effects of 25-hydroxy vitamin D (25[OH]D) on T lymphocyte subsets and sputum smear conversion during antituberculosis (TB) treatment. METHODS: A total of 120 newly diagnosed patients with active pulmonary TB were collected and classified into vitamin D sufficiency group, vitamin D insufficiency group, and vitamin D deficiency group according to serum 25(OH)D levels. The clinical data and sputum smear conversion were collected and serum 25(OH)D and T lymphocyte subsets were also measured and compared. RESULTS: Our data showed that 25(OH)D levels reached the lowest point at two months of anti-TB treatment. Significant differences existed in the increase of CD4+ and CD8+ T cells on the basis of vitamin D levels. The vitamin D sufficiency group had a significantly higher increase of CD4+ T cells during six months of anti-TB treatment and CD8+ T cells after four months of anti-TB treatment than the other groups. Vitamin D had no effect on the time-to-sputum smear conversion (vitamin D sufficiency group: adjusted hazard ratio: 1.27, 95% confidence interval [CI]: 0.78-2.06); vitamin D insufficiency group: adjusted hazard ratio: 1.05, 95% CI: 0.63-1.75)]. CONCLUSION: Through null effects on sputum smear conversion, vitamin D may have a beneficial effect on the increase of CD4+ and CD8+ T cells during anti-TB treatment.

ENPP1/PC-1 gene K121Q polymorphism is associated with obesity in European adult populations: evidence from a meta-analysis involving 24,324 subjects.

OBJECTIVE: Findings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP-1) or plasma cell membrane glycoprotein 1 (PC-1) gene single nucleotide polymorphism (K121Q, rs1044498) and genetic susceptibility to obesity. However, such relationship is not reproduced by some currently available studies. In this context, the present study is aimed to quantitatively analyze the association of K121Q variant with obesity in all published case-control studies in European adult populations. METHODS: Published literature from PubMed, EMBASE, and ISI web of science databases were retrieved. The studies evaluating the association of ENPP1/PC1 gene K121Q polymorphism with obesity were included, in which sufficient data were presented to calculate the odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Ten case-control studies meeting the inclusion criteria identified a total of 24,324 subjects including 11,372 obese and 12,952 control subjects. The meta-analysis results showed a statistically significant association of K121Q with obesity [OR (95%CI): 1.25 (1.04-1.52) P=0.021] under a recessive model of inheritance (QQ vs. KK+KQ) without heterogeneity or publication bias. CONCLUSIONS: The results from the present study have indicated that ENPP1/PC1 Q121 variant may increase the risk of obesity and that more well-designed studies based on a larger population will be required to further evaluate the role of ENPP1/PC1 gene K121Q polymorphism in obesity and other related metabolic syndromes.

Compensatory adaptation and diversification subsequent to evolutionary rescue in a model adaptive radiation.

Biological populations may survive lethal environmental stress through evolutionary rescue. The rescued populations typically suffer a reduction in growth performance and harbor very low genetic diversity compared with their parental populations. The present study addresses how population size and within-population diversity may recover through compensatory evolution, using the experimental adaptive radiation of bacterium Pseudomonas fluorescens. We exposed bacterial populations to an antibiotic treatment and then imposed a one-individual-size population bottleneck on those surviving the antibiotic stress. During the subsequent compensatory evolution, population size increased and leveled off very rapidly. The increase of diversity was of slower paces and persisted longer. In the very early stage of compensatory evolution, populations of large sizes had a greater chance to diversify; however, this productivity-diversification relationship was not observed in later stages. Population size and diversity from the end of the compensatory evolution was not contingent on initial population growth performance. We discussed the possibility that our results be explained by the emergence of a "holey" fitness landscape under the antibiotic stress.

Uncontrolled hypertension increases risk of all-cause and cardiovascular disease mortality in US adults: the NHANES III Linked Mortality Study.

Clinical trials had provided evidence for the benefit effect of antihypertensive treatments in preventing future cardiovascular disease (CVD) events; however, the association between hypertension, whether treated/untreated or controlled/uncontrolled and risk of mortality in US population has been poorly understood. A total of 13,947 US adults aged ≥18 years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used to conduct this study. Mortality outcome events included all-cause, CVD-specific, heart disease-specific and cerebrovascular disease-specific deaths, which were obtained from linked 2011 National Death Index (NDI) files. During a median follow-up of 19.1 years, there were 3,550 all-cause deaths, including 1,027 CVD deaths. Compared with normotensives, treated but uncontrolled hypertensive patients were at higher risk of all-cause (HR = 1.62, 95%CI = 1.35-1.95), CVD-specific (HR = 2.23, 95%CI = 1.66-2.99), heart disease-specific (HR = 2.19, 95%CI = 1.57-3.05) and cerebrovascular disease-specific (HR = 3.01, 95%CI = 1.91-4.73) mortality. Additionally, untreated hypertensive patients had increased risk of all-cause (HR = 1.40, 95%CI = 1.21-1.62), CVD-specific (HR = 1.77, 95%CI = 1.34-2.35), heart disease-specific (HR = 1.69, 95%CI = 1.23-2.32) and cerebrovascular disease-specific death (HR = 2.53, 95%CI = 1.52-4.23). No significant differences were identified between normotensives, and treated and controlled hypertensives (all p > 0.05). Our study findings emphasize the benefit of secondary prevention in hypertensive patients and primary prevention in general population to prevent risk of mortality later in life.

Cognition, serum BDNF levels, and BDNF Val66Met polymorphism in type 2 diabetes patients and healthy controls.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is associated with cognitive deficits. However, their pathophysiological mechanisms are still unknown. Recent study suggests that brain-derived neurotrophic factor (BDNF) is correlated with cognitive deficits in T2DM patients. This study was to determine whether altered serum BDNF levels and cognitive deficits depended on the BDNF Val66Met polymorphism in T2DM. RESULTS: The BDNF Val66Met polymorphism may not contribute directly to the susceptibility to T2DM. The total and nearly all index scores (all p < 0.01) except for the attention and visuospatial/constructional indexes (both p > 0.05) of RBANS were markedly decreased in T2DM compared with healthy controls. Serum BDNF levels were significantly lower in patients than that in controls (p < 0.001), and BDNF was positively associated with delayed memory in patients (p < 0.05). The Met variant was associated with worse delayed memory performance among T2DM patients but not among normal controls. Moreover, serum BDNF was positively associated with delayed memory among Met homozygote patients (ß = 0.29, t = 2.21, p = 0.033), while serum BDNF was negatively associated the RBANS total score (ß = -0.92, t = -3.40, p = 0.002) and language index (ß = -1.17, t = -3.54, p = 0.001) among Val homozygote T2DM patients. CONCLUSIONS: BDNF gene Val66Met variation may be associated with cognitive deficits in T2DM, especially with delayed memory. The association between lower BDNF serum levels and cognitive impairment in T2DM is dependent on the BDNF Val66Met polymorphism. METHODS: We recruited 311 T2DM patients and 346 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), serum BDNF levels, and the BDNF Val66Met polymorphism.

Sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway: An experimental study.

OBJECTIVE: To study whether sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway. METHODS: H9c2 myocardial cell lines were cultured and divided into control group (C group), hypoxia reoxygenation group (H/R group), sevoflurane pretreatment + hypoxia reoxygenation group (SP group) and sevoflurane combined with Compound C pretreatment + hypoxia reoxygenation group (ComC group), and the cell proliferation activity and apoptosis rate, myocardial enzyme levels in culture medium as well as the expression of apoptosis genes and p-AMPK in cells were determined. RESULTS: p-AMPK expression in cells of H/R group was significantly lower than that of C group, SP group was significantly higher than that of H/R group; cell proliferation activity value and Bcl-2 expression in cells of H/R group were significantly lower than those of C group, SP group were significantly higher than those of H/R group, ComC group were significantly lower than those of SP group; apoptosis rate, LDH, CK and AST levels as well as the Bax and Caspase-3 expression in cells of H/R group were significantly higher than those of C group, SP group were significantly lower than those of H/R group, ComC group were significantly higher than those of SP group. CONCLUSIONS: Sevoflurane pretreatment can activate AMPK signaling pathway to inhibit the myocardial apoptosis caused by hypoxia reoxygenation.

Short sleep duration predicts risk of metabolic syndrome: a systematic review and meta-analysis.

Sleep duration has been suggested to play a key role in the development of metabolic syndrome (MS). However, the results have been inconsistent. The objective of this study was to clarify the association between sleep duration and MS risk. PubMed and Embase databases were searched for eligible publications. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using random- or fixed-model. A total of 12 studies (18,720 MS cases and 70,833 controls) were included in the meta-analysis. Short sleep duration was significantly associated with increased risk of MS (OR = 1.27, 95%CI = 1.09-1.47, p = 0.002). Long sleep duration was not associated with increased risk of MS (OR = 1.07, 95%CI = 0.87-1.32, p = 0.535). Similar results were found in both men and women. The sensitivity analysis confirmed the stability of the results and no publication bias was detected. The present meta-analysis suggests that short rather than long sleep duration is significantly associated with risk of MS. Large-scale well-design prospective studies are required to further investigate the association between sleep duration and MS risk.

Nut consumption in relation to cardiovascular disease risk and type 2 diabetes: a systematic review and meta-analysis of prospective studies.

BACKGROUND: Many prospective cohort studies have investigated the association between nut consumption and risk of coronary artery disease (CAD), stroke, hypertension, and type 2 diabetes (T2D). However, results have been inconsistent. OBJECTIVE: We aimed to investigate the association between nut consumption and risk of CAD, stroke, hypertension, and T2D. DESIGN: PubMed and EMBASE databases were searched up to October 2013. All prospective cohort studies of nut consumption and risk of CAD, stroke, hypertension, and T2D were included. Summary RRs with 95% CIs were estimated by using a fixed- or random-effects model. RESULTS: A total of 23 prospective studies (9 studies for CAD, 4 studies for stroke, 4 studies for hypertension, and 6 studies for T2D) from 19 publications were included in the meta-analysis. There were 179,885 participants and 7236 CAD cases, 182,730 participants and 5669 stroke cases, 40,102 participants and 12,814 hypertension cases, and 342,213 participants and 14,400 T2D cases. The consumption of each 1 serving of nuts/d was significantly associated with incident CAD (RR: 0.81; 95% CI: 0.72, 0.91; P < 0.001) and hypertension (RR: 0.66; 95% CI: 0.44, 1.00; P = 0.049). However, there was no association between the consumption of each 1 serving of nuts/d and risk of stroke (RR: 0.90; 95% CI: 0.71, 1.14) or T2D (RR: 0.80; 95% CI: 0.57, 1.14). CONCLUSIONS: A higher consumption of nuts was associated with reduced risk of CAD and hypertension but not stroke or T2D. Large randomized controlled trials are warranted to confirm the observed associations.

Intake of fruit juice and incidence of type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Several prospective studies have been conducted to examine the relationship between fruit juice intake and risk of incident type 2 diabetes, but results have been mixed. In the present study, we aimed to estimate the association between fruit juice intake and risk of type 2 diabetes. METHODS: PubMed and Embase databases were searched up to December 2013. All prospective cohort studies of fruit juice intake with risk of type 2 diabetes were included. The pooled relative risks (RRs) with 95% confidence intervals (CIs) for highest vs. lowest category of fruit juice intake were estimated using a random-effects model. RESULTS: A total of four studies (191,686 participants, including 12,375 with type 2 diabetes) investigated the association between sugar-sweetened fruit juice and risk of incident type 2 diabetes, and four studies (137,663 participants and 4,906 cases) investigated the association between 100% fruit juice and risk of incident type 2 diabetes. A higher intake of sugar-sweetened fruit juice was significantly associated with risk of type 2 diabetes (RR = 1.28, 95%CI = 1.04-1.59, p = 0.02), while intake of 100% fruit juice was not associated with risk of developing type 2 diabetes (RR = 1.03, 95% CI = 0.91-1.18, p = 0.62). CONCLUSIONS: Our findings support dietary recommendations to limit sugar-sweetened beverages, such as fruit juice with added sugar, to prevent the development of type 2 diabetes.

Association between common polymorphism near the MC4R gene and obesity risk: a systematic review and meta-analysis.

BACKGROUND: Genome-wide association studies on Europeans have shown that two polymorphisms (rs17782313, rs12970134) near the melanocortin 4 receptor (MC4R) gene were associated with increased risk of obesity. Subsequently studies among different ethnic populations have shown mixed results with some confirming and others showing inconsistent results, especially among East Asians and Africans. We performed a comprehensive meta-analysis of various studies from different ethnic populations to assess the association of the MC4R polymorphism with obesity risk. METHODS: We retrieved all published literature that investigated association of MC4R variants with obesity from PubMed and Embase. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. RESULTS: A total of 61 studies (80,957 cases/220,223 controls) for rs17782313 polymorphism (or proxy) were included in the meta-analysis. The results suggested that rs17782313 polymorphism was significantly associated with obesity risk (OR=1.18, 95%CI=1.15-1.21, p<0.001). Similar trends were observed among subgroups of Europeans and East Asians, adults and children, studies with high quality score, and for each five MC4R polymorphisms independently. CONCLUSIONS: The present meta-analysis confirms the significant association of MC4R polymorphism with risk of obesity. Further studies should be conducted to identify the causal variant and the underlying mechanisms of the identified association.

Angiotensin-converting enzyme I/D polymorphism is not associated with type 2 diabetes in a Chinese population.

OBJECTIVE: A role for the angiotensin-converting enzyme (ACE) gene has been suggested in the aetiology of type 2 diabetes (T2DM). However, results have been inconsistent. In this study, we performed a meta-analysis to further clarify the association between ACE I/D polymorphism and T2DM risk in a Chinese population. METHODS: PubMed, EMBASE, CNKI and Wan Fang Data were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a fixed-effects model or random-effects model. RESULTS: : A total of 41 studies (4708 cases and 5368 controls) for the association between ACE I/D polymorphism and T2DM in a Chinese population were identified. The pooled ORs for the association between ACE I/D polymorphism and T2DM risk were not statistically significant under all genetic models (co-dominant model: DD vs. II: OR = 1.17, 95% CI 0.97-1.42 and ID vs. II: OR = 1.01, 95% CI 0.93-1.10; dominant model: OR = 1.06, 95% CI 0.94-1.19; multiplicative model: OR = 1.08, 95% CI 0.98-1.18). Although a marginally significant association was observed under a recessive model (OR = 1.17, 95% CI 1.00-1.36), robustness of this estimate could not be established under additional sensitivity analyses. CONCLUSIONS: : The meta-analysis presented in this study indicated that ACE I/D polymorphism may not be associated with the risk of T2DM in the Chinese population.