HLA-DRB1 Allele Polymorphisms Research Articles

Human leukocyte antigen (HLA)-DRB1 allele polymorphisms and systemic sclerosis

Objectives: Human leukocyteantigen (HLA) is the most important gene for immune system regulation. Although studies have evaluated the association between HLA-DRB1 allele polymorphisms and systemic sclerosis (SSc), their results are still controversial. We performed a meta-analysis to assess the association of HLA-DRB1 alleles with risk of SSc.Methods: Electronic database were systematically searched for articles, a total of 11 case–control studies including 3268 cases and 5548 controls were analyzed. Odds ratio (ORs) and 95% confidence intervals were used to assess the association of HLA-DRB1 alleles with SSc. The relationship between SSc-related autoantibodies and DRB1 alleles was also analyzed.Results: In the overall analysis, four alleles (DRB1*04:03, DRB1*08, DRB1*11, and DRB1*11:04) increased the risk of SSc; however, five alleles (DRB1*07, DRB1*11:01, DRB1*13, DRB1*13:01, and DRB1*14) had the opposite effect. Analysis of subgroups by ethnicity indicate that DRB1*11:01 and DRB1*13:01 confer a protective effect in Caucasians, while DRB1*11:04 was associated with a higher risk of SSc. For Asian, DRB1*13:02 was found to be a protective factor. In addition, the frequency of DRB1*11:04 alleles was significantly increased in ATA+ SSc patients compared with ATA− SSc patients.Conclusion: DRB1*04:03, DRB1*08, DRB1*11, and DRB1*11:04 were associated with the risk of SSc. Additionally, DRB1*11 and DRB1*11:04 were association with ATAs.

Association between HLA-A and HLA-DRB1 allele polymorphisms and susceptibility to tuberculosis in southern Chinese population

To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population. The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population. The frequencies of HLA-A* 0101 and HLA-DRB1*1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4% vs 0.6%, χ2=10.788, P=0.001, Pc=0.016; 7.5% vs 0%, χ2=69.850, P < 0.0001); the frequencies of HLA-DRB1*1202 and HLA-DRB1*1401 alleles were significantly lower in this patient cohort than in the control group (10.4% vs 16.1%, χ2=9.845, P=0.002, Pc=0.044; 0% vs 3.1%, χ2=18.520, P < 0.001). The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A*0101, HLA-DRB1*1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1*1202, HLA-DRB1*1401 and the other 4 alleles can be protective genes in this population.

Association between HLA-A and HLA-DRB1 allele polymorphisms and susceptibility to tuberculosis in southern Chinese population

To investigate the correlation between tumor-associated macrophages (TAMs) and the development of high risk human papilloma virus (hr-HPV)-related cervical cancer. A total of 112 cases of cervical tissue were collected, including 16 normal cervical tissues, 55 cervical intraepithelial neoplasia (CIN) tissues and 41 squamous cervical cancer (SCC) tissues. The expression of CD163+ macrophages in the cervical tissues was detected by immunohistochemical method, and the results were analyzed in relation with the clinical data of the patients. Immunohistochemical analysis showed that the cell density of CD163+ macrophages increased progressively with the increase in the tissue malignancy, in the order of normal cervical tissue, CIN Ⅰ, CIN Ⅱ-Ⅲ, and SCC. Correlation analysis revealed a positive relationship between CD163+ macrophage density and tissue malignancy (P=0.000). The density of CD163+ macrophages was significantly upregulated in HR-HPV-positive SCC tissue (P < 0.05). CD163+ macrophages were positively correlated with cervical lymph node metastasis (P=0.005) and FIGO stage (P=0.004) of SCC. The expression of CD163+ macrophages is positively correlated with malignant transformation of cervical tissues, and hr-HPV infection is significantly correlated with CD163 expression level in the macrophages. CD163+ macrophages can be used as predictors of the occurrence and progression of cervical cancer caused by hr-HPV infection.

Impact of HLA-DRB1 allele polymorphisms on control of HIV infection in a Peruvian MSM cohort.

Associations between HLA class II polymorphisms and HIV control were assessed in a Peruvian MSM cohort. Among 233 treatment naïve HIV+ individuals, DRB1*13:02 was linked to elevated viral loads (P = .044) while DRB1*12:01 showed significantly lower viral set points (P = .015) and restricted a dominant T cell response to HIV Gag p24 (P = .038). The present work contributes to a better knowledge of the Peruvian immunogenetics and supports the important role of HLA class II restricted T cells in HIV control.

Association of HLA-DRB1 gene polymorphisms with hepatocellular carcinoma risk: a meta-analysis

The study aimed to assess the association between human leukocyte antigen (HLA)-DRB1 allele polymorphisms and hepatocellular carcinoma (HCC) susceptibility. Relevant case-control studies on HLA-DRB1 allele correlation with HCC risk published between 2000 and 2015 were searched and retrieved in literature database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. Total 16 articles including 2208 HCC patients and 3028 relevant controls were finally screened out. A total of 12 case-control studies including 2030 HCC patients and 2817 relevant controls were screened out. Thirteen alleles (HLA-DRB1 *01, *03, *04, *07, *08, *09, *10, *11, *12, *13, *14, *15, and *16) were reported. Overall, we found that HLA-DRB1 *1 and *11 allele polymorphisms were significantly associated with decreased the HCC risk (*1: OR=0.53, 95% CI: 0.29-0.96, P=0.04; *11: OR=0.58, 95% CI: 0.38-0.88, P=0.010); while *12 and *14 allele polymorphisms were significantly associated with increased the HCC risk (*12: OR=1.49, 95% CI: 1.08-2.07, P=0.02; *14: OR=1.89, 95% CI: 1.27-2.82, P=0.002) in a fixed-effect model. However, other HLA-DRB1 allele polymorphisms were not associated with HCC susceptibility (P>0.05). HLA-DRB1 *1 and *11 allele polymorphisms were protective factors, *12 and *14 allele polymorphisms were risk factors for HCC development. Future large-scale studies with more ethnicities are still needed.

Relationship between HLA-DRB1 allele polymorphisms and familial aggregations of hepatocellular carcinoma.

We explored the relationship between HLA-DRB1 allele polymorphisms and familial aggregation of hepatocellular carcinoma (fhcc). Polymerase chain reaction sequence-specific primers were used to determine HLA-DRB1 genotypes for 130 members of families with 2 or more liver cancer patients and for 130 members of families without any diagnosed cancers. The genotype profiles were then compared to explore the relationship between HLA-DRB1 gene polymorphism and fhcc. Of 11 selected alleles, the frequencies of DRB1*11 and DRB1*12 were significantly lower in the fhcc group than in no-cancer group (p < 0.05; odds ratio: 0.286; 95% confidence interval: 0.091 to 0.901; and odds ratio: 0.493; 95% confidence interval: 0.292 to 0.893). Differences in the frequencies of the other 9 alleles were not statistically significant in the two groups (p > 0.05). Our research suggests that if genetic factors play a role in fhcc, the deficiency in the DRB1*11 and DRB1*12 alleles might be the risk factor at work in Guangxi Zhuang Autonomous Region, P.R.C.

HLA-DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma.

Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p = 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p = 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.

Correlations between HLA-A, HLA-B and HLA-DRB1 Allele Polymorphisms and Childhood Susceptibility to Acquired Aplastic Anemia

To investigate the correlations between polymorphisms of human leukocyte antigen (HLA)-A, HLA-B and HLA-DRB1 alleles and childhood susceptibility to aplastic anemia (AA), 80 children with AA were investigated. Among the 80 children, 74 had severe AA (SAA). Blood samples were collected from 109 healthy children as the controls. High-resolution genotyping of HLA-A, HLA-B and HLA-DRB1 alleles was conducted using polymerase chain reaction amplification with sequence-specific primers and polymerase chain reaction amplification with sequence-based typing. The expression frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher and the frequencies of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in the AA group compared with those in the control group. In addition, the frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher and the frequencies of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in the SAA group compared with those in the control group. HLA-B*48:01 and DRB1*09:01 were correlated with childhood AA, and thus they may be susceptibility genes for childhood SAA. HLA-B*51:01, DRB1*03:01 and DRB1*11:01 are expressed at low levels in children with AA.

Distribution of HLA-DRB1 allele polymorphism in the Uyghur women with family history of cervical cancer

To study the distribution of HLA-DRB1 allele polymorphism in Uyghur women with family history of cervical cancer, and provide theoretical evidence for detection and follow-up of high risk persons for cervical cancer by detection of HLA-DRB1 allele polymorphism. The HLA-DRB1 13 alleles were detected in 1000 Uyghur women, all from Hotan Moyu county Karsay village by using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) assay. The frequencies of HLA-DRB1*15 in women with family history of cervical cancer (17.3%), mother (18.0%) and other relatives except mother (17.0%) who had suffered from cervical cancer were significantly higher than that in the control group (9.7%, all P < 0.05). The frequencies of HLA-DRB1*04 in women with family history (16.8%) and other relatives except mother (20.7%) were significantly higher than that in the control group (12.7%, all P < 0.05). The frequencies of HLA-DRB1*03 in women with family history (2.6%) and other relatives except mother (1.1%) were significantly lower than that in the control group (6.3%, all P < 0.01). The frequencies of HLA-DRB1*12 in women with family history of cervical cancer (2.3%) and mother suffered from cervical cancer (1.5%) were significantly lower than that in the control group (5.7%, all P < 0.05). The frequencies of HLA-DRB1*14 in women with family history of cervical cancer (5.4%) and mother who suffered from cervical cancer (3.0%) were significantly lower than that in the control group (8.4%, all P < 0.05). There are similarity and difference in distribution of HLA-DRB1 allele polymorphisms between the Uyghur women with family history of cervical cancer from Hotan Moyu county and those from southern Xingjiang area. In general, the distribution of HLA-DRB1 allele polymorphism in women with family history of cervical cancer is similar to that reported in abroad. The results of this study support the role of susceptible and protective HLA gene detection in screening high risk persons for this cancer among Uyghur women from cervical cancer high risk areas in Xinjiang.

HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma.

To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province. HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers(PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics. Allele frequency (AF) of HLA-DRB1*0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs 0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1*0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles. HLA-DRB1*0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1*0901 may be susceptible to esophageal carcinoma.