ABSTRACT
Objective: To explore the characteristics of the association between the triglyceride glucose (TyG) index and nonfatal cardio-cerebrovascular disease risk in a community population. Method: This was a prospective cohort study. From December 2011 to April 2012, the first investigation was conducted among subjects with more than 40-year old who were from Shijingshan district and Pingguoyuan community in Beijing. The second investigation was conducted from April to October 2015. All the subjects were divided into three groups according to the tertile of the TyG index at baseline. The multivariate Cox proportional risk regression model was established to explore the correlation between the TyG index and nonfatal cardio-cerebrovascular disease risk and the Kaplan-Meier survival curve of the TyG index group was drawn. Subgroup analyses were performed according to age, gender, body mass index, type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to determine the correlation characteristics between the TyG index and nonfatal cardio-cerebrovascular disease among subgroups. Results: A total of 9 577 subjects were finally included to analyze. The mean follow-up time of this study was (34.14±3.84) months. During the follow-up, 363 subjects (3.8%) occurred nonfatal cardio-cerebrovascular disease. The multivariate Cox regression analysis results showed that the hazard ratio (HR) of nonfatal cardio-cerebrovascular disease in the high TyG index group was 1.54 (95%CI 1.19-1.98), 1.60 (95%CI 1.23-2.10), and 1.57 (95%CI 1.20-2.05) in the three models, compared with the low TyG index group. The Kaplan-Meier analysis showed that the risk of nonfatal cardio-cerebrovascular disease increased from the low-TyG index group to the high-TyG index group (P=0.015). In the six subgroups analysis, only gender was shown to have a significant interaction effect with the TyG index and nonfatal cardio-cerebrovascular disease risk. In the female population, the risk of nonfatal cardio-cerebrovascular disease is significantly increased with the increase in the TyG index level (P<0.001). Conclusions: A high TyG index is independently related to the increased risk of nonfatal cardio-cerebrovascular disease in the Beijing community population. Gender has a significant interaction with the TyG index and nonfatal cardio-cerebrovascular disease risk. Therefore, the TyG index may be a useful marker to predict the nonfatal cardio-cerebrovascular disease risk of a community population.
Subject(s)
Cerebrovascular Disorders , Diabetes Mellitus, Type 2 , Humans , Female , Adult , Glucose , Diabetes Mellitus, Type 2/epidemiology , Risk Factors , Beijing/epidemiology , Blood Glucose/analysis , Prospective Studies , Triglycerides , Biomarkers , Risk AssessmentABSTRACT
Objective: To summarize and analyze the clinical features and etiologies in hospitalized patients with syndrome of inappropriate antidiuretics (SIAD) during the past 25 years. Methods: All data of 128 patients with SIAD admitted to Chinese PLA General Hospital since January 1991 to January 2016 were collected. SIAD was diagnosed based on the 1957 criterion. Results: (1) The most frequent causes of increased inappropriate secretion of vasopressin were malignant tumors, lung diseases (e. g. pneumonia), and central nervous system diseases, in which malignant tumors accounted for 38.28% of the SIAD. (2) During the past 25 years, the proportion of malignant diseases declined from 4/7 to 35.29%, while, the proportion of pulmonary infection increased from 1/7 to 35.29% (P<0.05). (3) The patients with malignant tumors had the lowest serum sodium and serum osmolality among all SIAD patients. (4) CT scan had a high diagnostic value for chest and brain detection. (5) Among three SIAD subjects with unknown reasons at onset, two were diagnosed with small cell lung cancer and one with gastric cancer during follow-up. Conclusion: The etiology of SIAD is complex and it could be attributed to multifarious etiological factors. Malignant tumors account for the largest proportion of all patients, and pulmonary infection was ranked in second place. Cautions on tumors have to be taken when serum sodium of a SIAD patient is below 118.1 mmol/L.
Subject(s)
Central Nervous System/pathology , Hyponatremia/diagnosis , Inappropriate ADH Syndrome/diagnosis , Inappropriate ADH Syndrome/etiology , Neurophysins , Protein Precursors , Vasopressins , Central Nervous System Diseases , Humans , Hyponatremia/pathology , Inappropriate ADH Syndrome/complications , Inappropriate ADH Syndrome/pathology , Neoplasms/pathology , ThoraxABSTRACT
Objective: To investigate the prevalence of stroke and risk factors for stroke in middle-aged and elderly population in Beijing. Methods: A population based cross sectional survey was conducted among 19 145 subjects (males: 6 732; females: 12 413) aged ≥40 years from 3 communities in Shijingshan district of Beijing from November 2011 to August 2012. The information of subjects' demographic characteristics, lifestyle and histories of diabetes mellitus, hypertension and dyslipidemia were collected. The oral glucose tolerance test or a standard meal test was performed. Non-fatal stroke was reported by the subjects. Blood specimen were collected for detecting fasting blood glucose, TC, TG, HDL-C, LDL-C, HbA1c and 2-h blood glucose. Results: The overall prevalence of stroke was 3.3%, and the gender specific prevalence was 4.8% in males and 2.5% in females. The standardized prevalence based on 2010 population census data was 3.2%, 2.5% and 3.9%, respectively. The overall prevalence of smoking, overweight or obesity, hypertension, hyperglycemia and dyslipidemia was 45.2%, 60.4%, 52.7%, 51.5%, and 64.6% in males, respectively, and 2.2%, 55.1%, 42.2%, 45.6%, 67.4% in females, respectively. Conclusion: The prevalence of stroke was higher in males than in females in the middle aged and elderly people in Beijing. The smoking rate was significantly higher in males than in females. The prevalence of overweight or obesity, hypertension, and hyperglycemia were all higher in males than in females.
Subject(s)
Smoking , Adult , Aged , Beijing , Blood Glucose , Cross-Sectional Studies , Diabetes Mellitus , Dyslipidemias , Female , Humans , Hypertension , Male , Middle Aged , Overweight , Prevalence , Risk Factors , StrokeABSTRACT
Human leukocyte antigen (HLA)-G molecule acts as a potential factor for the regulation of immune responses and its expression in virus-infected cells may enable them to escape immunosurveillance. Besides its polymorphic promoter region, the 3' untranslated region (UTR) seems to play an important role in regulating HLA-G expression. In this study, we investigated the influence of HLA-G 14 bp (rs66554220) and +3142 (rs1063320) polymorphisms in 179 women with active human papillomavirus (HPV) infection and 143 age-matched, unrelated, HPV-negative, normal Chinese Han population. Our findings showed that frequency of the allele +3142 C [31.3% vs 44.4%, odds ratio (OR) = 0.57, Pc < 0.01] and the genotype +3142 CC (10.6% vs 21.7%, OR = 0.43, Pc = 0.012) was significantly decreased in HPV infected patients compared with normal controls. Furthermore, the haplotype -14 bp/C was associated with a reduced risk for HPV infection (OR = 0.57, Pc = 0.001). Our findings also showed that HLA-G homozygous +14 bp/+14 bp genotype was significantly associated with an increased risk for HPV18 infection (OR = 12.95, P < 0.01), whereas HLA-G heterozygous +14 bp/-14 bp genotype increased risk for HPV58 (OR = 5.55, P < 0.05). Furthermore, frequency of the haplotype +14 bp/G was significantly increased in HPV18 infected patients (60.0% vs 27.3%, OR = 4.00, Pc < 0.05). Taken together, our results supported a role of the HLA-G 3' UTR polymorphisms as a susceptible factor for the active HPV infection, and suggested a possible interference of the HLA-G molecule in the response to virus infection.
Subject(s)
3' Untranslated Regions/genetics , Genetic Predisposition to Disease , HLA-G Antigens/genetics , Papillomavirus Infections/genetics , Papillomavirus Infections/immunology , Polymorphism, Genetic , Adult , Aged , Case-Control Studies , Female , Genetic Association Studies , Haplotypes/genetics , Humans , Middle Aged , Papillomaviridae/classification , Papillomaviridae/physiology , Papillomavirus Infections/virology , Young AdultABSTRACT
The inhibitor of growth 2 (ING2) is a member of lNG family, involved in cell cycle regulation, DNA repair, apoptosis and senescence, and participating in chromatin remodeling and transcriptional regulation by histone modification. Recent researches suggest ING2 plays roles in carcinogenesis both as tumor suppressor gene and ongocene depending on tumor types and cell status. Here, we investigated the status of ING2 in a series of 64 Chinese non-small cell lung cancer (NSCLC)patients using immunohistochemistry (IHC) and confirmed the results with Western blotting. RT-PCR results revealed the expression level of ING2 was consistent with mRNA level. The IHC results showed that ING2 protein expression was significantly decreased in NSCLC samples compared with normal lung tissues (PSubject(s)
Adenocarcinoma/genetics
, Biomarkers, Tumor/genetics
, Carcinoma, Non-Small-Cell Lung/genetics
, Carcinoma, Squamous Cell/genetics
, Homeodomain Proteins/genetics
, Lung Neoplasms/genetics
, Receptors, Cytoplasmic and Nuclear/genetics
, Tumor Suppressor Proteins/genetics
, Adenocarcinoma/metabolism
, Adenocarcinoma/secondary
, Aged
, Biomarkers, Tumor/metabolism
, Blotting, Western
, Carcinoma, Non-Small-Cell Lung/metabolism
, Carcinoma, Non-Small-Cell Lung/secondary
, Carcinoma, Squamous Cell/metabolism
, Carcinoma, Squamous Cell/secondary
, Female
, Follow-Up Studies
, Homeodomain Proteins/metabolism
, Humans
, Immunoenzyme Techniques
, Lung Neoplasms/metabolism
, Lung Neoplasms/pathology
, Lymphatic Metastasis
, Male
, Middle Aged
, Neoplasm Staging
, Prognosis
, RNA, Messenger/genetics
, Real-Time Polymerase Chain Reaction
, Receptors, Cytoplasmic and Nuclear/metabolism
, Reverse Transcriptase Polymerase Chain Reaction
, Tumor Suppressor Proteins/metabolism
ABSTRACT
Alteration of human leukocyte antigen (HLA) expression, such as decreased HLA I (HLA-A, -B and -C) antigens and elevated nonclassical HLA I antigens (HLA-E, -F and -G), was reported to have an unfavorable prognosis in various cancers. In our study, HLA-F expression in 105 primary esophageal squamous cell carcinoma (ESCC) lesions and 62 case-matched adjacent normal tissues, and HLA I antigens among 68 cases were analyzed by immunohistochemistry. Data revealed that HLA-F expression was observed in 58.1% (61/105) of the ESCC lesions and in 54.8% (34/62) of the normal esophageal tissues. Among the 62 case-matched samples, HLA-F expression (lesion vs. normal tissue) was upregulated, unchanged and downregulated in 13 (21.0%), 6 (9.6%) and 43 (69.4%) cases, respectively. Patients with HLA-F positive had a worse survival than those with HLA-F negative (p = 0.040). Patients with upregulated HLA-F expression (lesion vs. normal tissue) had significantly worse survival than those with HLA-F unchanged and downregulated (p = 0.010). Furthermore, decreased HLA I expression was observed in 41.2% (28/68) patients and was with worse prognosis in comparison to those with preserved HLA I expression (p = 0.001). Multivariate analysis using Cox's proportional hazards model revealed that upregulated HLA-F expression (p = 0.026) and downregulated HLA I expression (p = 0.013) could be an independent unfavorable prognostic factor. In conclusion, our study provided the evidence that alteration of HLA I and HLA-F antigen expression was associated with survival in patients with ESCC.
Subject(s)
Carcinoma, Squamous Cell/immunology , Esophageal Neoplasms/immunology , Histocompatibility Antigens Class I/biosynthesis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Down-Regulation , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic/immunology , Histocompatibility Antigens Class I/genetics , Humans , Immunohistochemistry/methods , Male , Middle Aged , Prognosis , Up-RegulationABSTRACT
Human leukocyte antigen (HLA)-G could contribute to escape of cancer cells from host anti-tumor responses, and its potential clinical relevance in various malignancies was also addressed. However, the prognostic value of HLA-G in acute myeloid leukemia (AML) remains debated. In this study, HLA-G expression in malignant blasts was analyzed from 77 de novo AML patients (AML-M2, n=26; AML-M3, n=24; AML-M4, n=10; AML-M5, n=17) with flow cytometry. The proportion of HLA-G expressing blasts varied from 0% to 93.96% (median: 0.42%; 95% CI: 0-89.0%). Blasts with 0.5% or fewer HLA-G expressing were defined as negative according to its expression in normal CD34(+)CD45(+) cells (n=20, range: 0-0.5%; median: 0.13%; 95% CI: 0-0.42%). HLA-G expression status on leukemic blasts was not associated with the clinical parameters such as patient age at diagnosis, sex, sub-type of AML, percentage of blasts at diagnosis. Survival analysis revealed that HLA-G expression status on leukemic blasts is unrelated to the prognosis (p=0.884). The mean overall survival time for the HLA-G negative and positive patients was 20.7 months (95% CI: 16.1-25.3) and 20.1 months (95% CI: 14.3-25.8), respectively. Taken together, our findings indicated that HLA-G expression is of no significance for the prognosis of patients with AML.
Subject(s)
Antigens, CD34/biosynthesis , HLA-G Antigens , Leukemia, Myeloid, Acute/diagnosis , Leukocyte Common Antigens/biosynthesis , T-Lymphocytes/immunology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antigens, CD34/immunology , Child , Female , Flow Cytometry , Gene Expression , HLA-G Antigens/analysis , HLA-G Antigens/genetics , HLA-G Antigens/immunology , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Leukocyte Common Antigens/immunology , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index , Sex Factors , Survival Analysis , T-Lymphocytes/pathologyABSTRACT
Interleukin 1 receptor antagonist (IL-1Ra) is an important anti-inflammatory molecule encoded by the IL1RN gene. The polymorphism of IL1RN characterized by variable numbers of an 86 bp tandem repeat (VNTR) sequence in intron 2 has been described. Moreover, frequencies of the IL1RN alleles vary among different ethnics. In the present study, we analysed the IL1RN polymorphism in intron 2 in 256 Chinese Han and 252 Chinese She individuals. Four alleles including IL1RN*1, *2, *3 and IL1RN*4 were identified in this study. Data revealed that the distribution of the IL-1RN genotypes and allele was significantly different between the two Chinese populations (P < 0.001). Among them, 66.8% (171/256) and 86.5% (218/252) were homozygous for the allele IL-1RN*1 in Chinese Han and She individuals respectively. Homozygosity for allele IL-1RN*2 was only observed in Chinese Han with the percentage of 0.8% (2/256). Heterozygosity for IL-1RN*1/2, IL1RN*1/3 and IL1RN*1/4 was 30.9% (79/256), 0.4% (1/256) and 1.2% (3/256) in Chinese Han, whereas only heterozygosity for IL-1RN*1/2 was found in Chinese She (13.5%, 34/252). Frequencies of the most common allele IL-1RN*1 and IL-1RN*2 were 83.0% and 16.2% for Chinese Han and 93.3% and 6.7% for Chinese She respectively. The rare allele IL-1RN*3 and IL-1RN*4 was only observed in the Chinese Han population with the frequency of 0.2% and 0.6% respectively. Our findings suggested that the ethnic background plays an important role in IL-1Ra gene variation in different populations.
Subject(s)
Asian People/genetics , Interleukin 1 Receptor Antagonist Protein/genetics , Minisatellite Repeats/genetics , Polymorphism, Genetic , China/ethnology , Gene Frequency , Genotype , HumansABSTRACT
Interleukin-1 receptor antagonist (IL-1Ra) has been supposed to play important roles in pregnancy. The purpose of this study was to evaluate the association between the polymorphisms of IL-1Ra gene (IL1RN) variable number tandem repeat (VNTR) in intron 2 with idiopathic recurrent spontaneous abortion (RSA). Ninety-two RSA patients and hundred normal women with at least one live birth and no history of miscarriage were included in the study. Frequencies of the IL1RN alleles and genotypes were determined. Data revealed that the prevalence of IL1RN allele and genotype was not significant between the RSA and control group (all P > 0.05). Our finding indicated that the polymorphism VNTR of IL1RN gene in intron 2 may not be a risk factor for RSA in the Chinese Han population.
Subject(s)
Abortion, Habitual/genetics , Interleukin 1 Receptor Antagonist Protein/genetics , Polymorphism, Genetic , Adult , Case-Control Studies , China/ethnology , Female , Gene Frequency , Genotype , Humans , Pregnancy , Risk Factors , Young AdultABSTRACT
CD1 molecules are the major histocompatibility complex (MHC)-like glycoproteins specialized in capturing and presenting a variety of glycolipid to antigen-specific T-cells. There are five closely linked CD1 genes termed as CD1a, CD1b, CD1c, CD1d, and CD1e. CD1 gene features limited the polymorphism in exon 2 which encodes for the alpha1 domain. Few investigations on the allele frequencies of the CD1 genes have been reported to date; however, variation of CD1 allele frequency in different ethnics has been observed. In the current study, the CD1a, CD1d, and CD1e gene polymorphisms in exon 2 (alleles 01 and 02) in a group of normal Chinese Han and She individuals were analyzed. Similar allele prevalence was observed between the two populations. The CD1e allele frequency was 37.1% (allele 01); 62.9% (allele 02) and 39.3% (allele 01); 60.7% (allele 02) for Han and She populations, respectively. CD1e was the only polymorphic gene with a genotype frequency for Chinese Han (01/01, 11.0%; 01/02, 52.2%; 02/02, 36.8%) and She (01/01, 13.2%; 01/02, 52.1%; 02/02, 34.7%) individuals, respectively. No CD1a allele 01 and CD1d allele 02 were observed in either population. Our findings indicate that the polymorphism of CD1a, CD1d, and CD1e genes in exon 2 is very limited in the Chinese Han and She ethnics.
Subject(s)
Antigens, CD1/genetics , Antigens, CD1d/genetics , Asian People/genetics , Asian People/ethnology , Ethnicity/genetics , Exons/genetics , Humans , Polymorphism, Genetic , Sequence Analysis, DNAABSTRACT
HLA-G has been documented both in establishment of anti-tumour immune responses and in tumour evasion. To investigate the clinical relevance of HLA-G in non-small-cell lung cancer (NSCLC), expression status and potential significance of HLA-G in NSCLC were analysed. In this study, HLA-G expression in 101 NSCLC primary lesions and plasma soluble HLA-G (sHLA-G) from 91 patients were analysed with immunohistochemistry and ELISA, respectively. Correlations between HLA-G status and various clinical parameters including survival time were evaluated. Meanwhile, functional analysis of transfected cell surface HLA-G expression and plasma sHLA-G form NSCLC patients on natural killer (NK) cell cytolysis were performed. Data revealed that HLA-G was expressed in 41.6% (42/101) NSCLC primary lesions, while undetectable in adjacent normal lung tissues. HLA-G expression in NSCLC lesions was strongly correlated to disease stages (P= 0.002). Plasma sHLA-G from NSCLC patients was markedly higher than that in normal controls (P= 0.004), which was significantly associated with the disease stages (I versus IV, P= 0.025; II versus IV, P= 0.029). Patient plasma sHLA-G level (≥median, 32.0 U/ml) had a significantly shorter survival time (P= 0.044); however, no similar significance was observed for the lesion HLA-G expression. In vitro data showed that both cell surface HLA-G and patient plasma sHLA-G could dramatically decrease the NK cell cytolysis. Our findings indicated that both lesion HLA-G expression and plasma sHLA-G in NSCLC is related to the disease stage and can exert immunosuppression to the NK cell cytolysis, indicating that HLA-G could be a potential therapeutic target. Moreover, plasma sHLA-G in NSCLC patients could be used as a prognosis factor for NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/immunology , HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , Lung Neoplasms/immunology , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Membrane/metabolism , Cytotoxicity, Immunologic , Female , HLA Antigens/blood , HLA-G Antigens , Histocompatibility Antigens Class I/blood , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Killer Cells, Natural/immunology , Lung Neoplasms/blood , Lung Neoplasms/pathology , Male , Middle Aged , Survival AnalysisABSTRACT
The clinical relevance of human leucocyte antigen-G (HLA-G) has been postulated in malignancies. Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality worldwide; however, potential roles of HLA-G in HCC remain unknown. In the current study, HLA-G expression in 219 primary HCC lesions and their adjacent non-tumourous samples was analysed with immunohistochemistry. Correlations among HLA-G expression and various clinical parameters were evaluated. Meanwhile, functional analysis of transfected cell surface HLA-G expression on NK cell cytolysis was performed in vitro. HLA-G expression was observed in 50.2% (110/219) of primary HCC lesions, and undetectable in corresponding adjacent normal liver tissues. HLA-G expression was found in 37.8%, 41.9% and 71.4% of stage I, II and III HCC lesions, respectively. Data revealed that HLA-G expression in HCC was strongly correlated to advanced disease stage (I versus II, P= 0.882; I versus III, P= 0.020; II versus III, P= 0.037). HLA-G expression was also more frequently observed in elder patients (≥median 52 years, 57.5%versus 43.4%, P= 0.004). Meanwhile, plasma soluble HLA-G in HCC patients was significantly higher than that in normal controls (median, 92.49U/ml versus 9.29U/ml, P= 0.000). Functional assay showed that HLA-G expression in transfected cells could dramatically decrease the NK cell cytolysis (P= 0.036), which could be markedly restored by the blockade of HLA-G (P= 0.004) and its receptor ILT2 (P= 0.019). Our finding indicated that HLA-G expression was strongly correlated to advanced disease stage, and more frequently observed in elder patients. Its relevance to HCC progression might be result from the inhibition of NK cell cytolysis.
Subject(s)
Carcinoma, Hepatocellular/metabolism , HLA Antigens/biosynthesis , Histocompatibility Antigens Class I/biosynthesis , Liver Neoplasms/metabolism , Adult , Age Factors , Aged , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Blotting, Western , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Cytotoxicity, Immunologic/drug effects , Enzyme-Linked Immunosorbent Assay , Female , HLA Antigens/genetics , HLA Antigens/immunology , HLA-G Antigens , Hep G2 Cells , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Humans , Immunohistochemistry , K562 Cells , Killer Cells, Natural/cytology , Killer Cells, Natural/immunology , Liver Neoplasms/blood , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Tissue Array Analysis , TransfectionABSTRACT
Human leukocyte antigen-G (HLA-G) expression is a potential factor for the pathogenesis of virus infection. A 14 bp insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene is involved in the stability of HLA-G mRNA and HLA-G protein expression. Therefore, the HLA-G 14 bp polymorphism might be involved in human cytomegalovirus (hCMV) infection. To test a possible association between the HLA-G 14 bp deletion/insertion polymorphism and the active hCMV infection, in this study, a total of 54 patients with active hCMV infection and 165 age- and sex-matched, unrelated, normal Chinese Han population were genotyped for the 14 bp insertion/deletion polymorphism. Association of 14 bp polymorphism with hCMV urine DNA copies and the odds ratio (OR) of the polymorphism as a risk factor for active hCMV infection were analyzed. Our results showed that the prevalence of -14 bp/ -14 bp genotype in active hCMV patients was markedly increased [P(c) = 0.00034, OR = 3.31, 95% confidence interval (CI): 1.77-6.18], and similar significance was also observed for the frequency of -14 bp allele (P c = 0.0023, OR = 2.24, 95% CI: 1.38-3.64) when compared with that of healthy controls. Furthermore, urine hCMV DNA copies in patients with the -14 bp/ -14 bp genotype were significantly higher than those in patients with the +14 bp/ +14 bp genotype (P = 0.041). Our findings support a potential role of HLA-G 14 bp insertion/deletion polymorphism as a susceptible factor for the active hCMV infection.
Subject(s)
Cytomegalovirus Infections/genetics , Gastrointestinal Diseases/virology , HLA Antigens/genetics , Hepatitis/virology , Histocompatibility Antigens Class I/genetics , Pneumonia/virology , Polymorphism, Genetic/genetics , Purpura, Thrombocytopenic, Idiopathic/virology , Case-Control Studies , Child, Preschool , Cytomegalovirus/genetics , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/immunology , DNA, Viral/genetics , DNA, Viral/urine , Disease Susceptibility , Female , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/immunology , HLA-G Antigens , Hepatitis/genetics , Hepatitis/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Infant , Male , Mutagenesis, Insertional , Pneumonia/genetics , Pneumonia/immunology , Polymerase Chain Reaction , Purpura, Thrombocytopenic, Idiopathic/genetics , Purpura, Thrombocytopenic, Idiopathic/immunology , Sequence DeletionABSTRACT
Previous studies showed that human leukocyte antigen (HLA)-G is specifically upregulated in renal cell carcinoma (RCC). However, a larger cohort of RCC patients are necessary to obtain more information. In this study, 109 RCC primary lesions (clear cell, n = 95; chromophobe, n = 4; papillary, n = 4; collecting duct, n = 6) and corresponding adjacent tumor-negative renal tissues (n = 34) were analyzed for the HLA-G expression by immunohistochemistry (IHC). Meanwhile, plasma soluble HLA-G (sHLA-G) from 16 RCC patients and 144 sex- and age-matched normal individuals was detected by enzyme-linked immunosorbent assay. Correlations between lesion HLA-G expression and various clinical parameters were evaluated. Receiver-operating characteristic (ROC) curve analysis was used to determine the feasibility of HLA-G protein staining and sHLA-G as a diagnosis marker for RCC. IHC data showed that HLA-G was observed in 49.5% of clear cell, 50% of either chromophobe or collecting duct RCC lesions but undetectable in papillary RCC and tumor-negative renal tissues. This finding was consistent with the western blot results. sHLA-G was pronouncedly increased in RCC patients when compared with normal controls (median: 39.5 vs 19.2 U/ml, P = 0.002). However, no correlation was observed between HLA-G expression and various clinical parameters. We found that the area under ROC curve for HLA-G expression and sHLA-G was 0.739 [95% confidence interval (95% CI): 0.659-0.816, P = 0.000] and 0.733 (95% CI: 0.619-0.847, P = 0.002), respectively. Our findings indicated that, except the papillary RCC, other types of RCC could express HLA-G. Furthermore, both lesion HLA-G expression and plasma sHLA-G level might be a useful preoperative biomarker for diagnosis.
Subject(s)
Biomarkers, Tumor/immunology , Carcinoma, Renal Cell/immunology , Gene Expression , HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , Kidney Neoplasms/immunology , Age Distribution , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Feasibility Studies , Female , HLA-G Antigens , Histocompatibility Antigens Class I/analysis , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Humans , Immunohistochemistry , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , Middle Aged , ROC Curve , SolubilityABSTRACT
Unlike high polymorphic classical human leukocyte antigen (HLA) class I molecules, the genetic polymorphism of HLA-G is very limited. However, the prevalence of HLA-G alleles among different ethnic populations varied dramatically. The HLA-G null allele (HLA-G*0105N) is defined by a cytosine deletion (Delta C) at position 1597 in exon 3, which disrupts the reading frame and alters the expression of HLA-G proteins. The HLA-G*0105N allelic frequency was investigated in previous studies and possible roles were addressed. In the current study, a total of 310 Chinese Han and 260 Chinese She ethnic minority population had been genotyped for the G*0105N polymorphism. Marked difference was observed that the G*0105N allelic frequency in Chinese Han was 1.61%, while no copy of the null allele was observed in the Chinese She minority population (P(c) = 0.0073). Data also revealed that no homozygote of HLA-G*0105N allele exists in this Chinese Han population. Furthermore, significant difference was found for the frequencies of HLA-G*0105N both in Chinese Han and in Chinese She populations when compared with other ethnic populations. Taken together, our results indicated that ethnic variation of the HLA-G*0105N polymorphism among different ethnic populations is possibly the result of evolution. However, the advantages of the selection of this allele are necessary to be further investigated.
Subject(s)
Alleles , Asian People/genetics , HLA Antigens/genetics , China/ethnology , Genetic Variation , HLA-G Antigens , Humans , Polymorphism, GeneticABSTRACT
Soluble human leukocyte antigen-G (sHLA-G) functions as a multiple immunoregulator. A 14 bp insertion (+14 bp)/deletion (-14 bp) polymorphism in exon 8 of the HLA-G gene has been proposed to be associated with HLA-G mRNA stability and the expression of HLA-G. In the current study, a total of 150 normal Chinese Han population had been genotyped for the +14 bp/-14 bp polymorphism, and the expression of plasma sHLA-G was determined with enzyme-linked immunosorbent assay in these case-matched plasma. Data showed that genotype of 14 bp polymorphism was significantly associated with sHLA-G expression. Plasma sHLA-G level with the +14 bp/+14 bp genotype was dramatically lower than that with +14 bp/-14 bp (P = 0.004) and -14 bp/-14 bp genotypes (P = 0.003), while no dramatic difference was observed between the +14 bp/-14 bp and -14 bp/-14 bp genotypes (P > 0.05). In both males and females, plasma sHLA-G with the +14 bp/+14 bp genotype was also significantly lower when compared with other two respective 14 bp genotypes. Data also showed that sHLA-G expression was unrelated to gender. This study suggests that the 14 bp deletion polymorphism in the HLA-G gene plays an important role in sHLA-G expression and that interpretation of the potential biological functions of sHLA-G should be made with caution, taking the polymorphism into consideration.
Subject(s)
HLA Antigens/blood , HLA Antigens/genetics , Histocompatibility Antigens Class I/blood , Histocompatibility Antigens Class I/genetics , Sequence Deletion , Adult , Alleles , Female , Gene Expression , Gene Frequency , Genotype , HLA-G Antigens , Humans , Male , Middle Aged , Polymorphism, Genetic , Sequence Deletion/geneticsABSTRACT
Human leukocyte antigen-G (HLA-G) molecule exerts multiple immunoregulatory functions that have been suggested to contribute to the immune evasion of tumour cells. Studies on HLA-G expression in malignant haematopoietic diseases are controversial, and the functions of HLA-G on this context are limited. In the current study, HLA-G expression was analysed in different types of patients: de novo acute myeloid leukaemia (AML, n = 54), B cell acute lymphoblastic leukaemia (B-ALL, n= 13), chronic myeloid leukaemia (CML, n= 9) and myelodysplastic syndrome (MDS, n= 11). HLA-G expression was observed in 18.5% cases of AML, 22.2% in CML and 18.2% in MDS, but not in B-ALL patients. In AML, HLA-G-positive patients had a significant higher bone marrow leukaemic blast cell percentage when compared with that of HLA-G-negative patients (P < 0.01). Total T-cell percentage was dramatically decreased in HLA-G-positive patients (P < 0.05). Cytogenetic karyotyping results showed that all HLA-G-positive AML patients (n= 5) were cytogenetically abnormal, which was markedly different from that of HLA-G-negative patients (P < 0.01). Ex vivo cytotoxicity analysis revealed that HLA-G expression in AML leukaemic cells could directly inhibit NK cell cytolysis (P < 0.01). These findings indicated that HLA-G expression in AML is of unfavourable clinical implications, and that HLA-G could be a potential target for therapy.
Subject(s)
HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/immunology , Adult , B-Lymphocytes/immunology , Chromosome Banding , Cytotoxicity Tests, Immunologic , Female , Flow Cytometry , Fluorescein-5-isothiocyanate/metabolism , Fluorescent Dyes/metabolism , HLA Antigens/metabolism , HLA-G Antigens , Histocompatibility Antigens Class I/metabolism , Humans , Immunophenotyping , Karyotyping , Killer Cells, Natural/immunology , L-Lactate Dehydrogenase/metabolism , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , T-Lymphocytes/immunology , Tumor Cells, CulturedABSTRACT
The biological significance of human leukocyte antigen-G (HLA-G) is now beyond its initial concepts on the fetal-maternal immune regulation. HLA-G in various pathophysical conditions has been investigated, such as autoimmunity, tumor, inflammation and transplantation. HLA-G has also been postulated as a chemotherapy response marker both in protein and in genetic contexts. In the current study, a total of 640 Chinese Han and 258 Chinese She ethnic minority populations had been genotyped for the 14 bp insertion (+14 bp) and deletion (-14 bp) polymorphism in the HLA-G gene. Significant difference was observed for both the +14 bp/+14 bp (15.2% in the Han and 6.6% in the She; P = 0.00048, P(c) = 0.00097) and -14 bp/-14 bp (34.5% in the Han and 50.4% in the She; P = 1.05 x 10(-5), P(c) = 2.1 x 10(-5)) genotypes between the two populations, and similar significance was found for both +14 bp (40.3% in the Han and 28.1% in the She) and -14 bp allele distributions (P = 1.2 x 10(-6), P(c) = 2.4 x 10(-6)). Furthermore, frequencies of the 14 bp genotype and alleles both in the Chinese Han and in the Chinese She populations were compared with other ethnic populations. Data showed that dramatic variations between different ethnic populations were also observed for this polymorphism. In summary, our results indicate that heterogeneity of the 14 bp polymorphism in the HLA-G gene among different ethnic populations is possibly the result of evolution.
Subject(s)
HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Polymorphism, Genetic , Adult , Aged , Asian People/genetics , Base Sequence , DNA/genetics , Ethnicity/genetics , Evolution, Molecular , Female , Gene Frequency , HLA-G Antigens , Humans , Male , Middle Aged , Mutagenesis, Insertional , Sequence DeletionABSTRACT
BACKGROUND: Human leukocyte antigen-G (HLA-G) is an important immunotolerant which could be a part of the strategies applied by malignant cells applied to avoid host immunosurveillance. Aberrant expression of HLA-G has been found in ovarian carcinoma. The aim of this study was to evaluate the HLA-G expression in ovarian cancer tissues and to explore its function in vitro. MATERIALS AND METHODS: HLA-G expression in 33 primary ovarian carcinoma tissues was analyzed using immunohistochemistry with the anti-HLA-G monoclonal antibody (mAb) 4H84. Furthermore, the function of HLA-G in NK cell cytotoxicity was determined in vitro by cloning and expression of HLA-G on the ovarian carcinoma cell OVCAR-3. RESULTS: HLA-G expression was detected in 22/33 (66.7%) primary tumor tissues, but was absent in normal ovarian tissues (P<0.01). Cytotoxicity studies showed that HLA-G expression dramatically inhibits cell lyses by NK-92 cells (P<0.01), which could be restored by the anti-HLA-G conformational mAb 87G (P<0.01). CONCLUSION: HLA-G was expressed in a significant number of primary ovarian carcinoma tissues, and HLA-G expression in OVCAR-3 could directly inhibit NK-92 cell lysis. Taken together, our results indicated that expression of HLA-G plays an important role in evasion of ovarian cancer cells from host immunosurveillance.