Association of human leukocyte antigens-DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population.
ABSTRACT: BACKGROUND:Tuberculosis (TB) is the second-leading cause of death globally. Genetic polymorphisms in human leukocyte antigens (HLA)-DQB2, HLA-DPA1, and HLA-DPB1 may partly explain individual differences in TB susceptibility. METHODS:We performed a hospital-based case-control study to assess the genetic influence of single-nucleotide polymorphisms (SNPs) in the HLA (HLA-DPA, HLA-DPB, and HLA-DQB) on the development of TB. There were 248 TB-infected cases and 340 healthy controls in this study. RESULTS:The HLA-DQB2 rs7453920 genotype GG was applied as the reference group, the GA genotype was related to a considerably magnified risk of TB (GA vs. GG: adjusted OR = 1.547, 95% CI = 1.039-2.304, p = 0.032). Nevertheless, the other two SNPs were not associated with TB risk. Stratified analyses suggested that tobacco was associated with an increased risk of TB in HLA-DQB2 rs7453920 G>A. CONCLUSION:These results suggested that the functional HLA-DQB2 rs7453920 G>A polymorphism may contribute to the genetic susceptibility to TB. Nevertheless, the results were based on a limited sample size, and larger well-designed studies are expected to confirm these preliminary findings.
Project description:It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P?=?4.87×10(-14)), rs9276370 (HLA-DQA2, P?=?1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P?=?1.48×10(-11) and P?=?6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P?=?2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P?=?1.48×10(-12); OR?=?1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P?=?0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P?=?0.0132; OR?=?2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.
Project description:Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR?=?1.33, 95% CI: 1.04-1.71, P?=?0.026) and additive models (adjusted OR?=?1.30, 95% CI: 1.06-1.60, P?=?0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR?=?1.52, 95% CI: 1.01-2.28, P?=?0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR?=?1.37, 95% CI: 1.05-1.78, P?=?0.018).The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.
Project description:Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence.No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P < .05). Recipients with HLA-DQ (rs7453920) AG and AA genotype had lower direct bilirubin levels than GG genotype individuals, especially on the 14th day after surgery (17.80 vs. 5.35, P = .038). Patients with A alleles displayed earlier liver function recovery than patients with G alleles (7 vs. 6 months). No significant correlation was shown in HLA-DP rs3077 and rs9277535 with HBV infection or liver function recovery (P < .05).Our study concluded that HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were not significantly associated with HBV recurrence or HBV susceptibility, but HLA-DQ rs7453920 was related to prognosis of liver transplant recipients. HLA-DQ rs7453920 A might be used as an indicator of earlier recovery and better prognosis after transplantation.
Project description:Hepatocellular carcinoma (HCC) is etiologically linked with hepatitis B virus (HBV) and is the leading cause of death amongst 80% of HBV patients. Among HBV affected patients, genetic factors are also involved in modifying the risk factors of HCC. However, the genetic factors that regulate progression to HCC still remain to be determined. In this review, we discuss several single nucleotide polymorphisms (SNPs) which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection such as cyclooxygenase (COX)-2 expression specifically at COX-2 -1195G/A in Chinese, Turkish and Egyptian populations, tumor necrosis factor ? and the three most commonly studied SNPs: PAT-/+, Lys939Gln (A33512C, rs2228001) and Ala499Val (C21151T, rs2228000). In genome-wide association studies, strong associations have also been found at loci 1p36.22, 11q22.3, 6p21 (rs1419881, rs3997872, rs7453920 and rs7768538), 8p12 (rs2275959 and rs37821974) and 22q11.21. The genes implicated in these studies include HLA-DQB2, HLA-DQA1, TCF19, HLA-C, UBE2L3, LTL, FDX1, MICA, UBE4B and PG. The SNPs found to be associated with the above-mentioned genes still require validation in association studies in order to be considered good prognostic candidates for HCC. Screening of these polymorphisms is very beneficial in clinical experiments to stratify the higher or lower risk for HCC and may help in designing effective and efficient HCC surveillance programs for chronic HBV-infected patients if further genetic vulnerabilities are detected.
Project description:BACKGROUND: The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection. METHODS: This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children. RESULTS: Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0-44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model. CONCLUSION: Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.
Project description:Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB). The association between HBV infection and human leukocyte antigen- (HLA-) DQ polymorphism (rs2856718 and rs7453920) has been demonstrated in other studies; however, the results were controversial or inconclusive. Therefore, to derive a more precise estimation of the association, a meta-analysis was performed. Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association between HLA-DQ polymorphism (rs2856718 and rs7453920) and HBV infection risk. A total of 11 articles were used to evaluate the effect of the two polymorphisms on risk of HBV infection. The pooled data showed that HLA-DQ rs2856718-G polymorphism showed protection against HBV infection, and rs2856718-A was a risk factor for chronic HBV infection. The pooled risk estimates indicated that HLA-DQ rs7453920-A polymorphism was associated with decreased risk of HBV infection, and rs7453920-G serves as a risk factor in HBV infection. However, these stratified analyses were lacking credibility due to the limitation of correlational study numbers; further investigation on a large population and different ethnicities is warranted.
Project description:AIM: Many case-control studies have been performed in the recent past to investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism and tuberculosis (TB) susceptibility in various ethnic groups. However, these studies have produced inconsistent and contradictory results. In the present study, meta-analysis was performed to assess the association between CCL5 -403 G>A polymorphism and TB risk. METHODOLOGY: Quantitative synthesis was done for the published studies based upon association between CCL5 -403 G>A polymorphism and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models. RESULTS: A total of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were included in this meta-analysis. Variant A allele (A vs. G: p?=?0.035; OR?=?1.301, 95% CI?=?1.019 to 1.662) and variant homozygous (AA vs. GG; p?=?0.001; OR?=?1.520, 95% CI?=?1.202 to 1.923) carriers were significantly associated with TB susceptibility. Similarly, recessive model (AA vs. GG+GA: p?=?0.016; OR?=?1.791, 95% CI?=?1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous (GA vs. GG: p?=?0.837; OR?=?1.028, 95% CI?=?0.791 to 1.335) and dominant (AA+GA vs. GG: p?=?0.222; OR?=?1.188, 95% CI?=?0.901 to 1.567) models failed to show increased risk of developing TB. CONCLUSIONS: This meta-analysis suggests that there is a significant association between the CCL5 -403 G>A polymorphism and increased risk of TB. However, larger well-designed epidemiological studies with stratified case control and biological characterization may be helpful to validate this association.
Project description:Background:Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods:This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results:The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P<0.05). The rs7453920 genotype was significantly associated with the neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a threshold determined by receiver operating characteristic analysis. An elevated NLR was also an independent predictor of OS according to univariate and multivariate analyses (P<0.001). Conclusion:Our data show that HLA gene polymorphisms are associated with SI in patients with HBV-related HCC, and the absence of minor allele A (rs7453920) promotes SI and shortens OS.
Project description:Numerous epidemiological studies have reported the association between polymorphisms of Toll-like receptor 2 (TLR2) and susceptibility to tuberculosis (TB). However, the results remain inconclusive. Therefore, we performed a quantitative meta-analysis to evaluate associations between the polymorphism of Arg753Gln of the TLR2 gene and susceptibility to TB.Three databases (PubMed, CNKI and Embase) were systematically searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) as our index were used to assess the relation between the TLR2 gene Arg753Gln polymorphism and risk of TB. Overall and subgroup analyses were conducted according to the available information.With a detailed selection, 7 eligible studies with 1486 cases and 1322 controls were identified in our meta-analysis. There was a significant difference between TLR2 gene Arg753Gln polymorphism and the risk of TB (additive model: P<0.01, OR=2.89, 95% CI: 2.13-3.91; GA vs. GG: P<0.01, OR=2.92, 95% CI: 2.09-4.08). Interestingly, subgroup analysis based on ethnicity indicated that TB risk was significantly increased in Asians (additive model: P<0.01, OR=3.17, 95% CI: 2.31-4.35; GA vs. GG: P<0.01, OR=3.29, 95% CI: 2.32-4.68); by contrast, there was no association found in whites (additive model: P=0.40, OR=0.57, 95% CI: 0.15-2.13; GA vs. GG: P=0.40, OR=0.57, 95% CI: 0.15-2.13).Our meta-analysis provides evidence that the TLR2 gene Arg753Gln polymorphism is a risk factor to TB, especially in Asian populations.
Project description:Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+ DCs and mechanisms of lesion formation remain incompletely defined. To identify candidate LCH CD1a+CD207+ DC precursor populations, gene-expression profiles of LCH lesion CD1a+CD207+ DCs were first compared with established gene signatures from human myeloid cell subpopulations. Interestingly, the CD1c+ myeloid DC (mDC) gene signature was most enriched in the LCH CD1a+CD207+ DC transcriptome. Additionally, the BRAFV600E allele was not only localized to CD1a+CD207- DCs and CD1a+CD207+ DCs, but it was also identified in CD1c+ mDCs in LCH lesions. Transcriptomes of CD1a+CD207- DCs were nearly indistinguishable from CD1a+CD207+ DCs (both CD1a+CD207low and CD1a+CD207high subpopulations). Transcription profiles of LCH lesion CD1a+CD207+ DCs and peripheral blood CD1c+ mDCs from healthy donors were compared to identify potential LCH DC-specific biomarkers: HLA-DQB2 expression was significantly increased in LCH lesion CD1a+CD207+ DCs compared with circulating CD1c+ mDCs from healthy donors. HLA-DQB2 antigen was identified on LCH lesion CD1a+CD207- DCs and CD1a+CD207+ DCs as well as on CD1c+(CD1a+CD207-) mDCs, but it was not identified in any other lesion myeloid subpopulations. HLA-DQB2 expression was specific to peripheral blood of patients with BRAFV600E+ peripheral blood mononuclear cells, and HLA-DQB2+CD1c+ blood cells were highly enriched for the BRAFV600E in these patients. These data support a model in which blood CD1c+HLA-DQB2+ mDCs with activated ERK migrate to lesion sites where they differentiate into pathogenic CD1a+CD207+ DCs.