The distribution of HLA-A,-B,and-DRB1 alleles and haplotypes in inhabitants of Guizhou Province of China

The present study was aimed to analyze the frequencies of human leukocyte antigen （HLA）-A, -B, and -DRB1 alleles and A-B-DRBI, A-B, A-DRB1 and B-DRB1 haplotypes in inhabitants of Guizhou province, China. All samples were typed in the HLA-A,-B, and -DRB1 loci using the polymerase chain reaction-reverse sequence spe- cific oligonucleotide probe （PCR-rSSOP） method and HLA polymorphisms were analyzed. A total of 18 HLA-A, 31 HLA-B, and 13 HLA-DRB1 alleles were found in the Guizhou population. The first two frequent alleles in the HLA-A, -B, and -DRB1 loci were A＊1 1（30.72%） and A＊02（30.65%）, B＊40（16.27%） and B＊46（16.27%）, and DRBl＊09（15.91%） and DRBl＊15（13.51%）, respectively. The most common haplotype was A＊02-B＊46- DRBl＊09（5.59%） in A-B-DRB1, A＊02-B＊46（I 1.73%） in A-B, B＊46-DRBl＊09（7.49%） in B-DRB1, and A＊02- DRBl＊09（8.08%） in A-DRB1. Some baplotypes with strong linkage disequilibrium （LD） were found not only in the common haplotypes, such as A＊33-B＊58, B＊30-DRB1＊07, and B＊33-DRB1＊03, but also in the rare haplotypes, such as A＊01-B＊37, B＊37-DRB1＊10, and A＊01-DRB1＊10. Guizhou inhabitants shared some characteristics of the Southern Chinese population but also had their own unique features. Overall, HLA polymorphism in Guizhou population was more consistent with that of Chengdu population than that of other populations in China.

Association of HLA Alleles(A, B, DRB1) and HIV-1 Infection in the Han Population of Hubei, China

The HIV susceptibility and resistance alleles in the HLA genes were determined by investigating the distribution characteristics of the HLA alleles（A, B, and DRB1） in HIV-infected individuals of the Han population in Hubei, and by comparing these alleles with HIV-negative individuals from the same area. A cohort of 424 HIV-1 infected individuals were chosen as study subjects, and 836 HIV-negative healthy subjects from the same area served as the control population. HLA-A, B, and DRB1 allele typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probes（PCR-SSOP） and polymerase chain reaction-sequencing based typing（PCR-SBT） techniques. Arlequin ver3.0 was used to analyze the allele and haplotype frequencies of HLA-A, B, and DRB 1, whereas Epi Info 7 and SPSS18.0 was used to analyze the differences in the HLA alleles between the HIV-1 positive and HIV-1 negative groups. A＊02：03, DRB1＊01：01, and DRB1＊15：01 alleles and their haplotypes as well as the HLA_Bw4-Bw6 hybrid showed a protective effect on HIV-1 infection. After adjusting for confounding factors such as age and sex, multivariate logistic regression analysis revealed that B＊15：02G, DRB1＊01：01, and DRB1＊15：01 subtypes were the resistance genes of HIV-1 infection, while B＊13：01 might increase susceptibility to HIV-1 infection. The correlation between A＊02：06 and B＊15：01G subtypes and HIV-1 susceptibility was independent of the age and sex of the host. This study demonstrated the influence of genetic factors in humans such as HLA polymorphism on individuals to resist HIV-1 infection. Association studies of HLA polymorphism, susceptibility/resistance to HIV-1 infection, and hosts＇ genetic background are of significant importance for research on HIV-1 pathogenesis and vaccine design.

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

BACKGROUND Polymorphisms of human leukocyte antigen(HLA)genes are suggested to increase the risk of gastric cancer(GC).AIM To investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+multiple(≥2)EPIYA-C repeats.METHODS The patient group comprised 94 patients[44 GC and 50 duodenal ulcer(DU)patients],and the control group comprised 86 individuals[(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori(H.pylori)].Polymerase chain reaction was performed for the amplification of the H.pylori cagA gene and typing of EPIYA motifs.HLA sequence-specific oligonucleotide(SSO)typing was performed using Lifecodes SSO typing kits(HLA-A,HLA-B HLA-C,HLA-DRB1,and HLA-DQA1-B1 kits).RESULTS The comparison of GC cases in terms of CagA+multiple(≥2)EPIYA-C repeats showed that only the HLA-DQB1*06 allele[odds ratio(OR):0.37,P=0.036]was significantly lower,but significance was lost after correction(Pc=0.1845).The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats,but this was not significant in the univariate analysis.We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion,and none of the HLA alleles were significantly associated with GC or DU.Also,none of the alleles were detected as independent risk factors after the multivariate analysis.On the other hand,in a multivariate logistic regression with no discriminative criterion,HLA-DQA1*01(OR=1.848),HLA-DQB1*06(OR=1.821)and HLA-A*02(OR=1.579)alleles were detected as independent risk factors for GC and DU.CONCLUSION None of the HLA alleles were detected as independent risk factors in terms of CagA+multiple EPIYA-C repeats.However,HLA-DQA1*01,HLA-DQB1*0601,and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis.We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.

Human leukocyte antigen(HLA)A-C-B-DRB1-DQB1 haplotype segregation analysis among 2152 families in China and the comparison to expectation-maximization algorithm result

Human leukocyte antigen(HLA)is the major histocompatibility complex for humans.Previous studies have shown that high-resolution HLA matching can reduce graft vs.host disease and improve the outcome of hematopoietic stem cell transplantation(HSCT).Unrelated donor HSCT is very important when patients have no HLA-identical sibling donors.However,the chance of finding an available unrelated donor is not equal for every patient.Previous studies in Western countries have found that the HLA haplotype frequency(HF)could help to predict the probability of identifying HLA allele-matched unrelated donors.[1]However,the HLA system shows ethnic diversity and regional disparity.Therefore,if we want to use the HLA haplotype tool in China,a reliable HLA haplotype database for the Chinese population needs to be established.

Role of human leukocyte antigen molecules in selecting potential donors for allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation （alloHSCT） has been used to treat a variety of hematologic malignancies and non-malignant diseases.Hematopoietic stem cell donor selection is based on identical human leukocyte antigen （HLA） related or unrelated donor matching with the recipient.Donor-recipient HLA mismatching has been associated with graft-versus-host disease （GVHD）,increased mortality and decreased disease free survival （DFS）.1 Not all patients are able to find a suitable donor,as no more than 25% of patients have an HLA-identical sibling.Much effort has been devoted to the establishment of bone marrow （BM） registries for HSCT.Keywords：human leukocyte antigen; transplantation; donor; genotyping

Staged microvascular anastomosis training program for novices：transplantation of both kidneys from one rat donor

Background Rat renal transplantation is an essential experimental model and requires greater microsurgical skills.Thus,training novices to perform quick and reliable microvascular anastomosis is of vital importance for rat renal transplantation.In this study,we developed and evaluated a staged microvascular anastomosis training program for novices,harvesting and transplanting both kidneys from one rat donor.Methods Five trainees without any prior microsurgical experience underwent a training program in which the goals were staged according to difficulty.Each trainee had to achieve satisfactory results as evaluated by a mentor before entering the next stage.Rat renal transplantation was accomplished by end-to-end technique with a bladder patch.In the intensive rat renal transplantation stage,the trainees required an average of 20 independent attempts at isotransplantation as final training assessment.Results After 2 months of intensive practice,all trainees had achieved stable and reproducible rat renal transplantation,with a satisfactory survival rate of 85.9% at postoperative Day 7.The total mean operative time was 78.0 minutes and the mean hot ischemia time was 26.2 minutes.With experience increasing,the operative time for each trainee showed a decreasing trend,from 90-100 minutes to 60-70 minutes.After 20 cases,the mean operative time of the trainees was not statistically significantly different from that of the mentor.Conclusion Harvesting and transplanting both kidneys from one rat donor after a staged microvascular anastomosis training program is feasible for novices without any prior microsurgical skills.

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobin A1 c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1 DM patients(duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1 DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.