The Influence of SLC22A3 Genetic Polymorphisms on Susceptibility to Type 2 Diabetes Mellitus in Chinese Population.

Background: Solute carrier family 22 member 3 (SLC22A3) gene had been reported to be associated with the efficacy of metformin in type 2 diabetes mellitus (T2DM). However, few studies reported the relationship between SLC22A3 polymorphism and T2DM. The aim of this study was to investigate the association of SLC22A3 polymorphism and susceptibility to T2DM in Chinese population. Methods: We identified SLC22A3 rs555754, rs3123636, rs3088442 genotypes of 450 T2DM patients and 220 healthy controls from the Chinese population. The association between SNPs of SLC22A3 and susceptibility of T2DM was evaluated. Results: The clinical characteristics were significantly different between T2DM patients and healthy controls. The polymorphisms of SLC22A3 rs555754 and rs3123636 were obviously associated with the susceptibility of T2DM which was adjusted for age, sex and BMI, while rs3088442 did not. And there was haplotype association of SLC22A3 rs3088442-rs3123636 with T2DM susceptibility. Conclusion: SLC22A3 rs555754 and rs3123636 polymorphisms were associated with the susceptibility to T2DM in Chinese Han population. Large sample size studies would be required to verify this association.

The Effect of Pretreatment Potential Resistance to NNRTIs on Antiviral Therapy in Patients With HIV/AIDS.

BACKGROUND: With the increasing coverage of antiretroviral therapy, concerns for the emergence and transmission of HIV drug resistance (HIVDR) are arising. HIVDR was divided into 5 levels: sensitive, potentially resistant, low resistant, intermediate resistant, and high resistant. Most of the articles on HIVDR involved low-level, intermediate-level, and high-level drug resistance to antiretroviral drug, and few articles deal with potential drug resistance. Treatment failure associated with the level of low-level, intermediate-level, and high-level resistance to antiretroviral drug has been reported. However, whether virological failure (VF) is related to potential resistance remains unclear. In this study, we aimed to describe the situation of potential resistance to antiretroviral drug and whether it is related to VF. METHODS: We analyzed the demographic, behavioral information, medical history, and drug resistance-associated mutation data from subjects. Drug resistance mutations at baseline and time of failure in patients suffering VF were detected by using the Vela automated next-generation sequencing platform. The χ2 test or Fisher exact test and logistic regression were used to assess the risk factors that contribute to VF in the potential drug-resistant people. RESULTS: The prevalence of overall pretreatment drug resistance was 7.06% (233/3300), and the prevalence of pretreatment potential resistance was 8.79% (290/3300). All these patients with pretreatment potential first-line drugs resistance showed potential resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and some of them had potential drug resistance to NNRTIs and NRTIs or NNRTIs and PIs; among these patients, 94.71% (179/189) had V179 D/E mutations. The VF rate of first-line treatment for potentially resistant people is 17.99%. CD4+ T-cell count ≤200 cells/L at antiretroviral therapy initiation are risk factors for the failure of first-line treatment. CONCLUSIONS: The prevalence of potential drug resistance among individuals with HIV and the VF rate of first-line treatment for potential drug-resistant people were high. To better optimize clinical management, prevention, and control of HIV, attention should be devoted to the potential resistance of nonnucleoside drugs.

A novel prediction model to evaluate the probability of CD4+/CD8+ cell ratio restoration in HIV-infected individuals.

BACKGROUND: Our study aimed to develop a clinical prediction model to evaluate the possibility of CD4+/CD8+ ratio restoration in HIV-positive individuals. METHODS: About 1980, HIV/AIDS patients initiated with antiretroviral treatment from 1 January 2013, to 30 December 2016, at Beijing Ditan Hospital and achieved persistent virological suppression during the 4 years follow-up were included in this study. Multivariate Cox proportional regression analysis was used to identify the independent risk factors and establish a predictive model. The model's performance was assessed using the area under the receiver operating characteristic and calibration plots. RESULTS: Overall, after 4 years of treatment, a total of 455 individuals (22.98%) restored their CD4+/CD8+ ratio (≥1). The area under the receiver operating characteristic was 0.782 and 0.743 in the deriving and validation cohort, respectively. The ultimate model included five indexes: age at AIDS diagnosis, albumin, and syphilis status, and baseline CD4+ and CD8+ values. A nomogram further visualized the model, and the calibration plots indicated high agreement of predicted and observed outcomes. CONCLUSION: Our prediction model might be practical and easily applied to recognize HIV/AIDS individuals most likely to benefit from modern antiretroviral therapy.

Prevalence of transmitted drug resistance among ART-naïve HIV-infected individuals, Beijing, 2015-2018.

OBJECTIVES: Transmitted drug resistance (TDR) is a critical ongoing public health challenge in HIV/AIDS therapy. We explore the prevalence of TDR, its patterns, its associated risk factors, and predicted drug sensitivity in Beijing between 2015 and 2018. METHODS: Retrospective data on TDR from 3265 antiretroviral therapy (ART)-naïve patients were collected at Beijing Ditan Hospital from 1 August 2014 to 31 July 2018. TDR was defined according to the Stanford Drug Resistance Mutations Database. TDR prevalence, pattern, risk factors, and predicted drug sensitivity were analysed. RESULTS: The overall prevalence of HIV-1 TDR was 6.68% (218 of 3265), including 0.77%, 3.64%, and 2.36% resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors, respectively. The thymidine analogue mutations (TAMs) M41L/LM (4, 0.12%) and non-TAMs mutations M184V/MV/MI (8; 0.24%) were the primary NRTI-associated resistance mutations. K103N/KN (NNRTI associated) and M46L/I/IMV/IM/ML (protease inhibitor associated) were the other major resistance mutations. Patients 40-59 years old who had the CRF08_BC subtype were identified as having higher risk for drug resistance mutation. CONCLUSIONS: The prevalence of TDR among ART-naïve individuals with HIV-1 in Beijing was at a moderate level. Long-time and continuous surveillance of HIV TDR is necessary step in the therapy of ART-naive patients.

Altered T-Cell Subsets are Associated with Dysregulated Cytokine Secretion of CD4+ T Cells During HIV Infection.

BACKGROUND: CD4+ T cells play a critical role in the regulation of immunopathogenesis in HIV infection. Previous studies have shown contradictory results of the CD4+ T-cell responses in people living with HIV (PLHIV). METHODS: A cross-sectional study was performed on 40 healthy controls, 134 ART-naïve PLHIV, and 34 individuals who experienced 3-year ART with low baseline CD4 count from 4 August 2016 to 23 January 2019. We determined the frequencies of CD4+ T-cell subsets and described the cytokine secretion pattern of total and subsets of CD4+ T cells in these individuals. RESULTS: We found that CD4+ T cells in PLHIV displayed enhanced secretion of pro-inflammation cytokines and polyfunctionality due to HIV disease progression (r = -0.282, P = 0.0035 for IFN-γ; r = -0.412, P = 0.0002 for TNF-α; r = -0.243, P < 0.0001 for GM-CSF; r = -0.252, P = 0.0093 for IFN-γ+ TNF-α+ cells). However, the altered T-cell subsets, as presented by the loss of naïve cells and expansion of memory/effector population in PLHIV, were associated with discordant results in total and subsets of CD4+ T cells. As major cytokine-producing T subsets, effector/memory CD4 subsets showed impaired cytokine production (P < 0.05). We further demonstrated that 3-year ART treatment could improve CD4 counts by increasing the pool of naïve T cells but could not restore cytokine secretion in CD4+ T-cell subsets (P < 0.05). CONCLUSION: These data identified the impaired capacity of cytokine secretion in CD4+ T-cell subsets due to HIV disease progression, and the altered T-cell subsets were associated with pseudo-elevation of cytokine production in total CD4+ T cells. This study collectively suggested the importance of therapies that can preserve and/or enhance the function of CD4+ T cells in strategies of HIV remission.

Glucose metabolism-related gene polymorphisms as the risk predictors of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a complex polygenic metabolic disease characterized by elevated blood glucose. Multiple environmental and genetic factors can increase the risk of T2DM and its complications, and genetic polymorphisms are no exception. This review is mainly focused on the related genes involved in glucose metabolic, including G6PC2, GCK, GCKR and OCT3. In this review, we have summarized the results reported globally and found that the genetic variants of GCK and OCT3 genes is a risk factor for T2DM while G6PC2 and GCKR genes are controversial in different ethnic groups. Hopefully, this summary could possibly help researchers and physicians understand the mechanism of T2DM so as to diagnose and even prevent T2DM at early time.

Prevalence and risk factors for bone mineral density changes in antiretroviral therapy-naive human immunodeficiency virus-infected adults: a Chinese cohort study.

BACKGROUND: Studies have reported that low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected patients; however, the factors that contribute to HIV-related BMD changes are yet to be fully understood. Due to the application of dual X-ray absorptiometry (DXA) among a select group of hospitals only, the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China. Thus, the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy (ART)-naive HIV-positive patients in China. METHODS: The assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients. Demographic and clinical data, as well as results of fasting blood tests were obtained from patients. Further, all patients underwent DXA scans to determine BMD, which was then used to classify patients with osteopenia/osteoporosis. The risk factors of reduced BMD were then evaluated using binary logistic regression. RESULTS: Among the 156 ART-naive HIV-infected participants, osteopenia and osteoporosis were diagnosed in 48.7% (76/156) and 4.5% (7/156) of patients, respectively. The lumbar spine was most likely to have reduced BMD (49.4% [77/156]), and the proportion of osteopenia in the left hip (32.7% [51/156]) was higher than in the right hip (24.4% [38/156]). In the lumbar spine, bone loss rate in the L1 section (60.9% [95/156]) was the most significant (L2, 53.2% [83/156]; L3, 45.5% [71/156]; L4, 52.6% [82/156]). Further analysis showed that, compared with the neck (26.9% [42/156] in the left, 18.6% [29/156] in the right) and the interior (15.4% [24/156] in the left, 13.5% [21/156] in the right), the trochanter had the greatest probability of reduced BMD (46.2% [72/156] in the left, 28.8% [45/156] in the right). In the risk factor analysis, low body mass index (BMI: <18.5 kg/m2) was positively associated with reduced BMD (Exp (B) = 39.743, 95% confidence interval: 3.234-488.399, P = 0.004), and was specifically positively correlated with BMD values at three sites (r = 0.335 at right hip, r = 0.327 at left hip, r = 0.311 at lumbar spine). CONCLUSION: Reduced BMD was found in the majority of ART-naive HIV-infected patients and BMI was identified as an additional risk factor for reduced BMD. Our results show that BMD reduction was simultaneously present in the left hip, right hip, and lumbar spine among nearly one fifth of patients. Our work highlights the importance of closely monitoring BMD in ART-naive patients and provides a foundation for the clinical intervention of bone demineralization in them.

Prevalence and Risk Factors of Cytopenia in HIV-Infected Patients before and after the Initiation of HAART.

BACKGROUND: Cytopenia is a frequent hematological disorder in patients with human immunodeficiency virus (HIV) infection. However, the distribution and risk factors of cytopenia in patients starting highly active anti-retrovirus treatment (HAART) and the effect of HAART on cytopenia were not fully investigated. METHODS: From November 2004 to August 2016, a retrospective study was conducted to evaluate the prevalence of cytopenia in 4325 HAART-naïve patients. Risk factors of cytopenia at baseline and on recovery from cytopenia were analyzed using logistic regression analysis after 24 months of HAART in Beijing Ditan Hospital. RESULTS: The prevalence of cytopenia was 19.1% in HIV-naïve patients. Risk factors for cytopenia in HAART-naïve patients were a CD4 cell count<200 cells/µL, femaleness, WHO stage IV, coinfection with hepatitis B virus (HBV), BMI <18.5 kg/m2, a viral load ≥100,000 copies/ml, and age ≥40 years. In total, 70.2% and 76.4% of patients with cytopenia recovered after 6 and 24 months of HAART, respectively. The predictors of patients without normal blood cells after 24 months HAART were a CD4 cell count of <200 cells/µL, femaleness, WHO stage IV, coinfection with hepatitis B virus (HBV), BMI <18.5 kg/m2, a viral load ≥100,000 copies/ml, and age ≥40 years. In total, 70.2% and 76.4% of patients with cytopenia recovered after 6 and 24 months of HAART, respectively. The predictors of patients without normal blood cells after 24 months HAART were a CD4 cell count of <200 cells/. CONCLUSION: Early detection could decrease the prevalence of HIV-related cytopenia, while starting HAART as early as possible seems to be effective for normalization of the blood cells in HIV-infected patients.

SREBP1 as a potential biomarker predicts levothyroxine efficacy of differentiated thyroid cancer.

BACKGROUND: SREBP1 is a well-known transcript factor regulating lipogenesis. It has been reported to play an important role in tumor progress in recent years. However, the roles of SREBP1 in differentiated thyroid cancer (DTC) are uncertain. Based on this, we aimed to investigate the expression of SREBP1 and the influence of SREBP1 on DTC patients. METHODS: qRT-PCR and immunohistochemistry were used to detect the expression of SREBPs in DTC tissues and the adjacent normal tissues. The following methods, including the MTS, colony-forming assay, flow cytometry and Hoechst staining were used to detect the biological function of thyroid cancer cells based on SREBP1 interference or not. RESULTS: the expression of SREBP1 was significantly different among DTCs, thyroid nodules and the adjacent normal tissues. Briefly, SREBP1 was upregulated follow with the malignancy, but there was no significant difference of SREBP2 between thyroid nodules and the adjacent normal tissues. Further, the ROC curve showed that SREBP1 has higher diagnostic value than SREBP2. SREBP1 expression was significantly related to the tumor size and lymph node metastasis in DTCs. In vitro, the proliferation of thyroid cancer cells was suppressed obviously after interfered with SREBP1, and the apoptotic cells was increased. Further, SREBP1 expression was also associated with the short-term efficacy of levothyroxine in DTC patients. CONCLUSION: this is the first time to report that SREBP1 is an oncogene and a pro-proliferation factor in thyroid cancer, indicating that SREBP1 may serve as a potential biomarker and therapeutic target in thyroid cancer.

Down-Regulation of APTR and it's Diagnostic Value in Papillary and Anaplastic Thyroid Cancer.

APTR has been employed as a potential biomarker attributing to it was involved in carcinogenesis and malignancy's progression. However, the roles of APTR in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) are unclear. In the present study, we aimed to explore the relative expression of APTR in PTC and ATC tissues and the relation between APTR expression and PTC clinicopathological features. We analyzed APTR expression in PTC and ATC by investigating data obtained from the Gene Expression Omnibus (GEO) database. Then, we tested 76-pair PTC and adjacent normal samples by qRT-PCR, and the result was in accordance with the analysis in GEO datasets. Chi-square (χ2) analysis was employed to evaluate the association between APTR and PTC clinical features. These results showed that APTR was negatively related to TNM stages, distant metastasis. In addition, we further evaluated the feasibility of using APTR to detect PTC and ATC patients by the receiver operating characteristic (ROC) and the area under curve (AUC). These findings implied that down-regulation of APTR is correlated with tumorigenesis, also indicated that the potential diagnostic value of APTR for detecting PTC and ATC patients.

LncRNAs SNHG12 and LINC00152 were associated with progression of patients with papillary thyroid carcinoma.

Aim: To investigate the clinical roles of LINC00152 and SNHG12 in papillary thyroid carcinoma (PTC). Methods: LINC00152 and SNHG12 expression was sought and analysis in gene expression omnibus, The Cancer Genome Atlas and GEPIA datasets. Tumor and adjacent normal tissues were collected from 97 PTC and 44 benign thyroid nodules patients. The expression was evaluated by quantitative real-time polymerase chain reaction. The association between the expression level and clinicopathologic characteristics was analyzed by χ2 test. Receiver operating characteristic curves were plotted to evaluate the diagnostic value. Results: The expression of SNHG12 and LINC00152 were significantly higher in PTC tissues than in adjacent normal tissues not only in gene expression omnibus database but the validated samples. More interesting, LINC00152 expression level was also significantly higher in PTC tissues than that in benign thyroid nodules. The upregulation of LINC00152 and SNHG12 was associated with the malignant progression of PTC. Receiver operating characteristic curve analysis also demonstrated that there was a good trend, which indicates that they may have certain diagnostic value. Conclusion: LINC00152 and SNHG12 might serve as serve as potential related molecules of PTC.

Down-regulation of DANCR acts as a potential biomarker for papillary thyroid cancer diagnosis.

Long non-coding RNAs (lncRNAs) have been reported to be dysregulated and play a crucial role in the progression of cancer. LncRNA DANCR has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including osteosarcoma, gastric cancer, breast cancer, hepatocellular carcinoma, and colorectal cancer. However, the expression profiles and biological relevance of DANCR in papillary thyroid cancer (PTC) have not yet been reported. In the present study, the expression level of DANCR in PTC tissues and adjacent normal tissues was detected by reverse transcription-quantitative PCR in PTC patients, and then we analyzed the association with clinical pathological characteristics of patients and DANCR expressions. These results demonstrated that the expression of DANCR was notably decreased in tumor tissues in comparison with adjacent normal tissues (P<0.001). Furthermore, the present study found that DANCR expression level was correlated to T grade (P<0.01) and TNM stage (P=0.017). The present study demonstrated that DANCR was associated with PTC aggressive clinical features and may serve as a diagnostic biomarker for detecting PTC patients.

Identification and validation of potential target genes in papillary thyroid cancer.

Thyroid cancer (TC) is one of the most common endocrine malignancies, and the incidence of TC has almost tripled over the past three decades. This increase may partially own to overdiagnosis and approximately 15-30% of cytological indeterminate thyroid nodules cannot be evaluated by means of fine-needle aspiration. The present study aimed to identify potential crucial genes of PTC and provide new sights into improving the diagnosis of thyroid lesions for future study. We adopted an integrated analysis of Gene expression profiles of PTC patients and adjacent normal controls and data from The Cancer Genome Atlas databases (TCGA). The differentially expressed genes (DEGs) were screened using the Limma package in R software. Connectivity Map (CMap) was used to predict potential drugs for PTC. STRING and Cytoscape software were employed to perform GO, KEGG pathway enrichment analysis and module analysis for DEGs. RT-qPCR was used to validate hub genes screened using module analysis. A total of 218 DEGs were screened, including 55 down-regulated and 163 up-regulated DEGs. GO analysis showed that these DEGs were primary enriched in cell adhesion, extracellular region and glycosaminoglycan binding. KEGG pathway analysis revealed that DEGs primarily participated in ECM-receptor interaction. PPI network and module analysis identified seven-hub genes, including FN1, SERPINA1, ECM1, MMRN1, PROS1, CFD, TIMP1. RT-qPCR results validated that the expression levels of seven-hub genes were consistent with the bioinformatics analysis. These findings have identified seven-hub genes which may helpful for the development of gene panel for thyroid nodules diagnosis.

Genetic polymorphism contributes to 131I radiotherapy-induced toxicities in patients with differentiated thyroid cancer.

AIM: To investigate the association between SNPs in DNA damage response pathways and toxicities following 131I radiotherapy of differentiated thyroid cancer (DTC). Materials & methods: We identified 22 functional SNPs of genes in DNA damage response pathways. MassArray was used to sequence SNP genotypes in 203 DTC patients. Hardy-Weinberg equilibrium and the associations between the two alleles of each SNP and toxicity reactions were evaluated using χ2 analysis. RESULTS: Ataxia-telangiectasia mutated (ATM) rs620815 T-allele carriers were at increased risk of 131I radiation-induced gastrointestinal reaction compared with C allele carriers. TNFα rs1800629 GA genotype may increase the incidence of neck pain compared with GG genotype. Furthermore, TNFα rs1800629, ATM rs11212570, NF-κß rs230493, and TGF-ß rs1800469, rs2241716 were associated with throat pain following 131I radiotherapy. CONCLUSION: The identified SNPs might serve as novel biomarkers for DTC treated with 131I radiotherapy.

Upregulation of long noncoding RNA MALAT1 in papillary thyroid cancer and its diagnostic value.

AIM: To investigate the expression level of lncRNA MALAT1 in papillary thyroid cancer (PTC) and evaluate its clinical diagnostic value as a biomarker in PTC. METHODS: MALAT1 lncRNA expression in tissues was detected by qRT-PCR. The diagnostic value of MALAT1 as a biomarker in PTC was evaluated with receiver operating characteristics. RESULTS: MALAT1 expression was upregulated in PTC tissues compared with paired corresponding noncancerous tissues. We also found that upregulated MALAT1 expression was correlated with tumor size, lymph node metastases (p = 0.011) and WHO disease stage. The area under the curve was 0.6320, 0.7192, 0.7089 and 0.7000 for PTC, lymph node metastasis, extrathyroidal extension and WHO disease stage prediction, respectively. CONCLUSION: Our finding suggests that MALAT1 may exert oncogenic function in PTC and may be a potential diagnostic marker for this cancer.

REST, not REST4, is a risk factor associated with radiotherapy plus chemotherapy efficacy in glioma.

BACKGROUND/AIM: Repressor element silencing transcription factor (REST) is a transcription repressor, expressed in several malignancies. This study aims to evaluate the prognostic values of REST and its splicing variant REST4 in glioma, and investigate the potential correlation between REST and REST4. METHODS: REST and REST4 expression values were evaluated by qRT-PCR in 89 patients with gliomas and 10 with normal brain tissues. RESULTS: Upregulation of REST was related to higher World Health Organization (WHO) grade, larger tumor size, higher ki67, and higher p53 positive rate. After radiotherapy+temozolomide (RT+TMZ) treatment, low REST expression patients could get better therapeutic efficacy (P=0.031). The positive rate of REST4 expression was only 13.5% in glioma tissues, and REST4 expression was not associated with clinical characteristics and REST expression in this study. CONCLUSIONS: REST was a prognostic factor in glioma, while REST4 was not. REST expression can be a predictor in evaluating the survival outcome of gliomas patients treated with RT+TMZ after surgery.

P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas.

Diffuse gliomas are the most common type of primary brain and central nervous system (CNS) tumors. Protein disulfide isomerases (PDIs) such as P4HB and PDIA3 act as molecular chaperones for reconstructing misfolded proteins, and are involved in endoplasmic reticulum stress and the unfolded protein response. The present study focused on the role of P4HB and PDIA3 in diffuse gliomas. Analysis of GEO and HPA data revealed that the expression levels of P4HB and PDIA3 were upregulated in glioma datasets. their increased expression was then validated in 99 glioma specimens compared with 11 non-tumor tissues. High expression of P4HB and PDIA3 was significantly correlated with high Ki-67 and a high frequency of the TP53 mutation. Kaplan-Meier survival curve and Cox regression analyses showed that glioma patients with high P4HB and PDIA3 expression had a poor survival outcome, P4HB and PDIA3 could be independent prognostic biomarkers for diffuse gliomas. In vitro, knockdown of PDIA3 suppressed cell proliferation, induced cell apoptosis, and decreased the migration of glioma cells. Furthermore, downregulation of P4HB and PDIA3 may contribute to improve the survival of patients who receive chemotherapy and radiotherapy. The data suggest that high expression of P4HB and PDIA3 plays an important role in glioma progression, and could predict the survival outcome and therapeutic response of glioma patients. Therefore, protein disulfide isomerases may be explored as prognostic biomarkers and therapeutic targets for diffuse gliomas.

Effect of AMP-activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population.

BACKGROUND: It is well known that AMP-activated protein kinase (AMPK) is a key factor affecting the development of type 2 diabetes mellitus (T2DM). The single nucleotide polymorphism (SNP) rs2746342 in the AMPK alpha 2 subunit gene (PRKAA2) has been found to be associated with susceptibility to T2DM in the Chinese Han population. The present study further investigates the association of PRKAA2 genotypes with susceptibility to T2DM and its complication, diabetic nephropathy. METHODS: The PRKAA2 genotypes of 406 T2DM patients and 214 controls from the Chinese Han population were determined with regard to SNPs rs10789038, rs2796498 and rs2746342. The association between these SNPs and susceptibility to T2DM and diabetic nephropathy was evaluated. The clinical characteristics differed significantly between T2DM patients and controls. RESULTS: After adjustment for age, sex and body mass index, there was an obvious relationship between T2DM and both rs10789038 (odds ratio [OR] 1.634; P = 0.015) and rs2796498 (OR 0.656; P = 0.030), but not rs2746342. There was haplotype association of PRKAA2 rs10789038-rs2796498-rs2746342 with T2DM susceptibility. In addition, rs2796498 was found to be related to the susceptibility to diabetic nephropathy. CONCLUSIONS: Polymorphisms in rs10789038 and rs2796498 are associated with the susceptibility to T2DM, and rs2796498 may be related to diabetic nephropathy.

Molecular mechanisms and potential prognostic effects of REST and REST4 in glioma (Review).

Glioma refers to a tumor of the brain and central nervous system, which is characterized by high incidence, high mortality and high recurrence rate. Although the association between glioma and the repressor element silencing transcription factor (REST) has been reported by numerous studies, the complicated regulatory mechanisms underlying REST remain unknown. REST is a transcriptional repressor that undergoes alternative splicing to produce splicing variants when transcribed. Previous studies have demonstrated that alternative splicing may serve a role in the outcome of glioma. The present review discussed the mutual relationship among REST, REST4 and glioma. It was concluded that increased REST expression in glioma may be associated with poor prognosis; and REST4, an AS variant of REST, also functions to regulate glioma by suppressing REST. In addition, the present review discussed the regulation of REST and its target genes in glioma, and identified factors that induce REST alternative splicing, particularly in glioma. These findings suggest that REST may be considered a prognostic factor, which can be predictive of patient outcome.

STK11 rs2075604 Polymorphism Is Associated with Metformin Efficacy in Chinese Type 2 Diabetes Mellitus.

Metformin is a classical oral antidiabetic drug, often recommended to be the first-choice treatment of type 2 diabetes mellitus (T2DM). Based on the previous research on STK11 and diabetes, we aimed to investigate the distributive characteristic of STK11 rs2075604 polymorphism and the potential influence of STK11 rs2075604 polymorphism on metformin efficacy among Chinese T2DM patients. There was no significant difference between T2DM patients (G = 64.8%, T = 35.2%) and healthy subjects (G = 62.7%, T = 37.2%) in STK11 rs2075604 genotype and allele frequencies. After 12 weeks of treatment, 62 patients were defined as the responders and 32 patients as nonresponders according to the decrease of HbA1c level. And the GT + TT genotype in STK11 rs2075604 can decrease HbA1c level more significantly than the GG genotype. Furthermore, the allele frequency of T in the STK11 rs2075604 was higher in the responders than the nonresponders (43.55% versus 26.56%). The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment. In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. This trial is registered with clinical study registration number NCT03155087.