Characteristics of culprit intracranial plaque without substantial stenosis in ischemic stroke using three-dimensional high-resolution vessel wall magnetic resonance imaging.

Background and aims: We aim to analyze the difference in quantitative features between culprit and non-culprit intracranial plaque without substantial stenosis using three-dimensional high-resolution vessel wall MRI (3D hr-vw-MRI). Methods: The patients with cerebral ischemic symptoms of the unilateral anterior circulation were recruited who had non-stenotic intracranial atherosclerosis (<50%) confirmed by computed tomographic angiographic (CTA) or magnetic resonance angiography (MRA). All patients underwent 3D hr-vw MRI within 1 month after symptom onset. 3D hr-vw-MRI characteristics, including wall thickness, plaque burden, enhancement ratio, plaque volume and intraplaque hemorrhage, and histogram features were analyzed based on T2-, precontrast T1-, and post-contrast T1-weighted images. Univariate and multivariate logistic regression analysis were used to identify key determinates differentiating culprit and non-culprit plaques and to calculate the odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 150 plaques were identified, of which 133 plaques (97 culprit and 36 non-culprit) were in the middle cerebral artery, three plaques (all culprit) were in the anterior cerebral artery (ACA) and 14 (11 culprit and three non-culprit) were in the internal carotid artery (ICA). Of all the quantitative parameters analyzed, plaque volume, maximum wall thickness, minimum wall thickness, plaque burden, enhancement ratio, coefficient of variation of the most stenotic site, enhancement ratio of whole culprit plaque in culprit plaques were significantly higher than those in non-culprit plaques. Multivariate logistic regression analysis found that plaque volume [OR, 1.527 (95% CI, 1.231-1.894); P < 0.001] and enhancement ratio of whole plaque [OR, 1.095 (95% CI, 1.021-1.175); P = 0.011] were significantly associated with culprit plaque. The combination of the two features obtained a better diagnostic efficacy for culprit plaque with sensitivity and specificity (0.910 and 0.897, respectively) than each of the two parameters alone. Conclusion: 3D hr-vw MRI features of intracranial atherosclerotic plaques provided potential values over prediction of ischemic stroke patients with non-stenotic arteries. The plaque volume and enhancement ratio of whole plaque of stenosis site were found to be effective predictive parameters.

Regional differences and the driving mechanism of relationships between rural household livelihood and ecosystem services:A case study in upstream watershed of Miyun Reservoir, China.

It is of great significance to link ecosystem and rural household welfare, with the aim to develop different strategies of rural household livelihood management and regional sustainable deve-lopment. Based on 1754 questionnaires of rural households in Beijing and Hebei within the upstream watershed of Miyun Reservoir, we analyzed the relationships between rural household welfare (defined by total income per rural household) and ecosystem reliance (expressed by an index of dependence on ecosystem services) by statistical and econometric methods. The relationships between rural household welfare and ecosystem reliance could be classified into four types, but with significant differences between Beijing and Hebei within the watershed. The rural household type of high welfare and low dependence had the highest proportion (33.9%) in Beijing. The average annual income and livelihood capitals of rural households in Beijing was significantly higher than that of Hebei Province. In Hebei Province, the dominant type was low welfare and high dependency (39.1%) that was the least popular one. The quality of human capital quality, social capital, and financial capital, which were crucial to human well-being, were significantly lower than that of Beijing households. The income of rural households in Hebei mainly depended on agricultural production (41.2%), which led to higher land utilization intensity. The natural resource and human capital quality significantly influenced rural household livelihood in Hebei. Maintaining suitable family size and age structure, improving education and skill levels, and strengthening payment for ecosystem services within low welfare households would be the key to form a good relationship between ecosystems and household welfare (the type of high welfare and low dependency).

Aneurysms in Takayasu's arteritis: a retrospective study of Chinese patients.

OBJECTIVES: Aneurysm formation can cause life-threatening complications in Takayasu's arteritis (TAK). The objective of this study was to evaluate the demographic, clinical and angiographic features, and outcomes of aneurysm secondary to TAK in Chinese patients. METHODS: The medical charts of patients diagnosed with TAK in Changhai Hospital between 2001 and 2017 were retrospectively reviewed. RESULTS: Aneurysms were identified in 66 (16.6%) of 397 patients with TAK. The mean age at onset was 30.4±11.5 years, with a male:female ratio of 1:2.7. Patients with aneurysm had a higher proportion of male (p<0.01), higher incidences of bruit, chest tightness and aortic regurgitation (all p<0.001), and a lower incidence of visual disturbances (p<0.01) as compared with patients without aneurysm. The prevalence of elevated ESR and CRP and ITAS2010 score were higher in patients with than without aneurysm (all p<0.01). Angiographic classification showed that type V (30.3%) was the most frequent pattern in patients with aneurysm though Type I was dominant in patients without aneurysm. Multiple aneurysms were found in 30.3% of patients and the most common site of aneurysms was abdominal aorta (22.1%). Glucocorticoids were prescribed in 86.4% of patients with aneurysm, and surgical procedures were performed in 80.3%. Five of 52 patients died during the median 3-year follow-up period. CONCLUSIONS: These findings could provide useful information on the demographical, clinical and angiographic features of TAK patients with aneurysm. Aneurysm formation in TAK may be associated with male gender and active vascular inflammation.

HIST1H3D: A promising therapeutic target for lung cancer.

HIST1H3D gene encodes histone H3.1 and is involved in gene-silencing and heterochromatin formation. HIST1H3D expression is upregulated in primary gastric cancer tissue. In this study, we explored the effects of HIST1H3D expression on lung cancer, and its mechanisms. HIST1H3D expression was measured by immunohistochemistry and RT-PCR in lung cancer tissues and human lung cancer cell lines. Cell proliferation was assessed by MTT assay. Flow cytometric analysis was used to determine cell cycle distribution and apoptosis. Levels of related proteins were detected by western blotting. Bioinformatics analysis was performed to investigate related signaling pathways. cDNA microarray analysis was performed to identify differentially expressed genes following HIST1H3D knockdown. HIST1H3D expression was upregulated in lung cancer tissue samples and the H1299 human lung cancer cell line (P<0.01). Regulation of HIST1H3D expression in nucleus of cells in lung cancer tissues was significant associated with tumor stage (P=0.02) and lymph node metastases (P=0.04). Downregulation of HIST1H3D expression led to suppression of proliferation and colony forming ability, cell cycle arrest at the G0/G1 phase, and promotion of cell apoptosis. The microarray data revealed 522 genes that were differentially expressed after HIST1H3D knockdown in H1299 cells. These genes were shown to be linked to numerous pathways, including the cell cycle, p53 signaling, and MCM. Western blot analysis confirmed upregulated expression of the THBS1 and TP53I3 genes, and downregulated expression of the CDK6, CDKN1 and CCNE2 genes. In conclusion, our results suggest that HIST1H3D is highly expressed in lung cancer cell lines and tissues. Furthermore, HIST1H3D may be important in cell proliferation, apoptosis and cell cycle progression, and is implicated as a potential therapeutic target for lung cancer.

Testin is a tumor suppressor in non-small cell lung cancer.

The Testin gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. It has been implicated in several types of cancers including prostate, ovarian, breast and gastric cancer. In the present study, we investigated the function of the candidate tumor-suppressor Testin gene in non-small cell lung cancer (NSCLC). In NSCLC cell lines, we observed lower expression of Testin compared to that noted in normal human bronchial epithelial cells. MTT assays, flow cytometry, clonogenic assay and invasion assay showed that the overexpression of the Testin gene inhibited cancer cell proliferation, invasion and colony formation. In tumor xenograft models, Testin markedly inhibited lung cancer cell xenograft formation and growth in athymic nude mice. Taken together, these data suggest that Testin plays an important role in the development and progression of NSCLC. Testin may be an effective novel target in NSCLC prevention and treatment.

Asbestos exposure and laryngeal cancer mortality.

OBJECTIVES/HYPOTHESIS: Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma. However, the link between asbestos exposure and other malignancies was not confirmed. The aim of the current meta-analysis was to provide a summary measure of risk for laryngeal cancer associated with occupational asbestos exposure. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases were searched for studies characterizing the association between asbestos and laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence interval (CI) of each study was combined using a fixed or random effect model. RESULTS: Significantly increased SMR for laryngeal cancer was observed when subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45-1.97, P < .001), with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I(2) = 0.0%). Effect estimates were larger for cohorts controlling for male subjects, Europe and Oceania, mining and textile industries, exposure to crocidolite, long study follow-up (>25 years), and SMR for lung cancer > 2.0. Publication bias was not detect by Begg test (P = .910) and Egger test (P = .340). CONCLUSIONS: Our study supports the association of exposure to asbestos with an increased risk of laryngeal cancer mortality among male workers. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1169-1174, 2016.

Meta-analysis for the Association of Apolipoprotein E ε2/ε3/ε4 Polymorphism with Coronary Heart Disease.

BACKGROUND: Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis. Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD. In recent years, numerous case-control studies have investigated the relationship of APOE polymorphism with CHD risk. However, the results are confusing. METHODS: To clarify this point, we undertook a meta-analysis based on 14 published studies including 5746 CHD cases and 19,120 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP, College Station, TX, USA). RESULTS: Overall, the analysis showed that carriers of APOE ε2 allele decreased risk for CHD (ε2 allele vs. ε3 allele: OR = 0.82, 95% CI: 0.75-0.90, P < 0.001; ε2 carriers vs. ε3 carriers: OR = 0.81, 95% CI: 0.73-0.89, P < 0.001), compared with those carrying ε3 allele, especially in Caucasian population. However, those with ε4 allele had a significant increased risk for CHD (ε4 allele vs. ε3 allele: OR = 1.34, 95% CI: 1.15-1.57, P < 0.001), especially in Mongoloid population. Potential publication bias was observed in the genetic model of ε4 versus ε3, but the results might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results were not materially alerted, suggesting the stability of our results. CONCLUSIONS: Taken together, our meta-analysis supported a genetic association between APOE gene and CHD. ε4 increased the risk of CHD, whereas ε2 decreased the risk of CHD.

Stomach cancer mortality among workers exposed to asbestos: a meta-analysis.

BACKGROUND: The relationship between asbestos and stomach cancer is not well understood because of small number of cases. This study aimed to determine the incidence and mortality of stomach cancer among workers exposed to asbestos based on a systematic review and meta-analysis approach. METHODS: Relevant English electronic databases were systematically searched for published studies characterizing the risk of developing stomach cancer as a result of asbestos exposure. Standardized mortality rate (SMR) for stomach cancer with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA. RESULTS: A total of 32 independent studies were included for the analysis. The overall SMR for stomach cancer was 1.19 (95% CI 1.06-1.34), with a moderate degree of heterogeneity across the studies (I(2) = 37.6%, P = 0.011). Being male, exposure to crocidolite, miners, studies conducted in Europe and Oceania, and long study follow-up (≥ 25 years) all contribute to significantly higher SMR. Significant publication bias was observed. CONCLUSION: Elevated risk of stomach cancer mortality was evidenced among workers exposed to crocidolite, especially male miners.

Micronutrients, their potential effect on patients with systemic sclerosis.

Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases.

INTRODUCTION: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. AREAS COVERED: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. EXPERT OPINION: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.

Epidemiology of syphilis infection among drug users at methadone maintenance treatment clinics in China: systematic review and meta-analysis.

Illicit drug trade has re-emerged in China since 1979 and the number of drug addicts had increased. Syphilis is mainly spread through sexual contact and blood. The incidence of syphilis is high among drug users. Methadone maintenance treatment (MMT) clinics have been implemented in China since 2004. The aim of this study was to estimate the prevalence and risk factors of syphilis among drug users at MMT clinics in China between 2004 and 2013. Chinese and English databases (CBM, CNKI, Weipu, Pubmed) of literature were searched for studies reporting syphilis among drug users in MMT clinics from 2004 to 2013. The prevalence estimates and risk factors were summarized through a systematic review and meta-analysis of published literatures. In all, 29 eligible articles with a total of 8899 drug users, were selected in this review. The pooled prevalence of syphilis infection was 7.78% (95%CI: 5.83%-9.99%). The meta-analyses demonstrated significant differences in syphilis infection rates between men and women (OR = 0.34 [95%CI: 0.26-0.45]) but not between drug users and non-intravenous drug users (OR = 0.82 [95%CI: 0.51-1.32]). Enhanced detection of syphilis and health promotion is warranted in MMT clinics in China.

The effectiveness of propranolol in treating infantile haemangiomas: a meta-analysis including 35 studies.

AIMS: Propranolol may have shown excellent results as a first line therapy in infantile haemangiomas (IHs) at all sites in the body, but this conclusion remains controversial. In an attempt to resolve this issue, we performed a meta-analysis. METHODS: A search of the literature using PubMed, MEDLINE, Cochrane Library databases and China National Knowledge Infrastructure (CNKI) was performed to identify studies which estimated the efficacy of propranolol therapy in infants with haemangiomas all sites of the body. The pooled odds ratio (OR) along with the corresponding 95% confidence intervals (CI) were assessed using a fixed effects model. RESULTS: Thirty-five studies involving 324 infantile haemangioma(IH) patients and 248 controls were retrieved and analyzed. The efficacy of propranolol was greater than other therapies in treating IHs (OR = 9.67, 95% CI 6.62, 14.12, P < 0.001). In a stratified analysis by sites of tumour, propranolol was a more effective therapy when compared with steroids (OR = 9.67, 95% CI 6.61, 14.15, P < 0.001), vincristine (OR = 9.00, 95% CI 2.15, 37.66, P = 0.003) and laser treatment (OR = 9.00, 95% CI 1.42, 57.12, P = 0.020) in treating cutaneous IHs (OR = 24.95, 95% CI 9.48, 65.64, P < 0.001), peri-ocular IHs (OR = 9.39, 95% CI 3.88, 22.71, P < 0.001), infantile airway haemangiomas (OR = 20.91, 95% CI 7.81, 55.96, P < 0.001) and infantile hepatic haemangiomas (OR = 9.89, 95% CI 1.20, 81.54, P = 0.033). CONCLUSION: The current meta-analysis provided strong evidence for propranolol as a first line therapy for IHs.

DNA repair gene XRCC1 polymorphisms and head and neck cancer risk: an updated meta-analysis including 16344 subjects.

BACKGROUND: DNA repair gene X-ray repair cross complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity and protection of cells from DNA damage. Sequence variation in XRCC1 gene may alter head and neck cancer (HNC) susceptibility. However, these results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 polymorphism and HNC risk, we undertook a meta-analysis involving 16,344 subjects. METHODS: A search of the literature by PubMed, Embase, Web of Science and China National Knowledge Infrastructure was performed to identify studies based on the predetermined inclusion criteria. The odds ratio (OR) with 95% confidence interval (CI) was combined using a random-effects model or a fixed-effects model. RESULTS: Twenty-nine studies consisting of 6,719 cases and 9,627 controls were identified and analyzed. Overall, no evidence of significant association was observed between XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln genotypes and the risk of HNC in any genetic models. Subgroup analyses according to ethnicity, tumor site, publication year, genotyping method also detected no significant association in any subgroup, except that oral cancer was associated with Arg194Trp variant in recessive model. Furthermore, no significant effect of these polymorphisms interacted with smoking on HNC risk was detected but Arg194Trp homozygous variant. CONCLUSION: In conclusion, this meta-analysis suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not involve in HNC susceptibility. Further studies about gene-gene and gene-environment interactions in different populations are required.

The effect of TGF-ß1 polymorphism on systemic sclerosis: a systematic review and pooled analysis of available literature.

Transforming growth factor-ß1 (TGF-ß1) plays an important role in the pathogenesis of systemic sclerosis (SSc). To investigate whether TGF-ß1 gene promoter polymorphisms were associated with the susceptibility of SSc, we performed a meta-analysis based on all available studies through PubMed, Elsevier Science Direct, Embase, and Chinese Biomedical, China National Knowledge Infrastructure and Google Scholar with the last report up to March 15, 2013. Crude odds ratios with 95% confidence intervals were used to estimate the strength of the association. A fixed or random effects model was adopted according to heterogeneity test. Heterogeneity among studies was evaluated using I (2) . Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Begg's and Egger's test. Totally, seven papers with 663 SSc patients and 908 healthy controls were subjected to the final analysis. These studies encompass seven for TGF-ß1 codon 10, three for codon 25 and three for -509C/T. We failed to detect any association of these promoter polymorphism with SSc susceptibility. For TGF-ß1 codon 10 polymorphism, subgroup analyses by race, genotype testing method and classification of SSc were further performed. Similarly, no association was observed. Significant heterogeneity was detected among the studies in all genetic models of TGF-ß1 codon 10 polymorphism. Publication bias was absent. Taken together, our meta-analysis did not provided an evidence of confirming association between TGF-ß1 (codon 10, codon 25, -509C/T) gene polymorphism and SSc. Nevertheless, due to smaller sample sizes, larger sample studies including different ethnic groups should be considered in future to confirm our results.

The risk of cancer development in systemic sclerosis: a meta-analysis.

OBJECTIVES: Systemic sclerosis is a multi-system disorder of connective tissue characterized by Raynaud's phenomenon and fibrosis of various organs. The risk of development of cancer in systemic sclerosis (SSc) has been extensively investigated with inconclusive results. To shed some light on the controversy, we conducted a meta-analysis of all published articles linking SSc to the risk of cancer development. METHODS: Relevant electronic databases were searched for English-language studies characterizing the association of cancers in patients with SSc. Standardized incidence rate (SIR) with its 95% confidence interval (CI) of each study was combined using a fixed/random effect model. RESULTS: A total of seven papers including 7183 SSc patients were identified, of which 7 reported the SIR for lung cancer, 4 for non-Hodgkin's lymphoma (NHL) and 4 for hematopoietic cancer and 7 for breast cancer. Compared with the general population, the combined SIR was 3.14 (95% CI: 2.02-4.89), 2.68 (95% CI: 1.58-4.56), 2.57 (95% CI: 1.79-3.68) and 1.09 (95% CI: 0.86-1.38), respectively. Significant heterogeneity was observed in lung cancer group (Q=26.13, P<0.001, I(2)=77%). Potential publication bias was absent. CONCLUSIONS: This present meta-analysis demonstrated an increased risk of lung, non-Hodgkin's lymphoma and hematopoietic cancers among patients with SSc, but not for breast cancer. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

Association of TGF-ß1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

Many case-control studies have investigated the role of TGF-ß1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95% confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-ß1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR=0.65, 95% CI=0.48-0.88, P=0.005; CC vs. CT+TT: OR=0.56, 95% CI=0.45-0.69, P=0.000; C vs. T: OR=0.81, 95% CI=0.71-0.93, P=0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-ß1 +869C/T promoter polymorphism and RA, especially in Asian population.

PADI4 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis.

The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg's test, and Egger's test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05-1.12), 1.17 (1.12-1.23), 1.26 (1.18-1.36), 1.17 (1.10-1.24), 1.30 (1.17-1.44), and 1.25 (1.11-1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose-response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.

Polymorphism M55V in gene encoding small ubiquitin-like modifier 4 (SUMO4) protein associates with susceptibility to type 1 (and type 2) diabetes.

BACKGROUND: The association between small ubiquitin-like modifier 4 (SUMO4) gene polymorphism and type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) has been investigated in several studies. We conducted a meta-analysis to evaluate the association of SUMO4 gene polymorphism with T1DM and T2DM susceptibility. METHODS: A meta-analysis was performed on the published studies before August 2011. The association of SUMO4 M55V polymorphism with T1DM and T2DM was evaluated. Meta-analysis was performed for genotypes AA versus GG, AA versus AG, AA versus AG + GG and A allele versus G allele in a fixed/random effect model. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association. RESULTS: Sixteen case-control studies including 9190 cases and 10 456 healthy controls were included. T1DM patients were divided into Asian and Caucasian subgroup. We detected a significant association of SUMO4 M55V polymorphism with T1DM in Asian population (A versus G: OR = 0.79, 95%CI = 0.72-0.86, p = 0.000) and a significant association of SUMO4 M55V polymorphism with T1DM in Caucasian population (A versus G: OR = 0.84, 95%CI = 0.73-0.97, p = 0.007). Included T2DM patients were all Asian. Meanwhile, a significant association of SUMO4 M55V polymorphism with T2DM was also found (A versus G: OR = 0.86, 95%CI = 0.79-0.94, p = 0.001). CONCLUSIONS: Our study demonstrates significant associations of SUMO4 M55V polymorphism with T1DM in Asian and Caucasian population and with T2DM in Asian population.

Association of cytotoxic T-lymphocyte associated antigen 4 gene polymorphism with type 1 diabetes mellitus: a meta-analysis.

To evaluate the association between costimulatory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus(T1DM), sixty-three published studies before December, 2011 were included. Meta-analysis was performed for each genotype in a random/fixed effect model. The combined odds ratio (OR) with 95% confidence interval (95%CI) was calculated to estimate the strength of the association. Overall, significant correlation was noted between CTLA-4 gene polymorphism (i.e. +49A/G, CT60A/G in a per-allele model) and the risk of T1DM (for +49A/G: OR=1.47, 95%CI=1.36-1.60, P<0.001; for CT60A/G: OR=1.31, 95%CI=1.18-1.45, P<0.001). However, no significant association was noted between C(-318)T polymorphism and T1DM. In the subgroup analysis, for +49A/G and CT60A/G, the statistically significant associations were also demonstrated in diverse racial descents (Caucasian and Asian) and age of onset (<20 years and >20 years). In conclusion, our results suggest that CTLA-4 polymorphism contributes to the susceptibility of T1DM.