1.Analysis of HPA1-16 and HLA-A, B gene polymorphisms among ethnic Han population from Shandong.
Yi ZHANG ; Yuan YU ; Wenben QIAO ; Yan LIU ; Juan ZHOU ; Jianhong XU ; Bing FAN ; Liyue JIANG ; Wenhua LIANG ; Chuanfu ZHU
Chinese Journal of Medical Genetics 2016;33(5):690-693
<b>OBJECTIVEb>To study the polymorphisms of human platelet antigen (HPA) 1-16 and human leukocyte antigen (HLA)-A and -B loci among ethnic Han population from Shandong.
<b>METHODSb>A total of 588 samples from platelet donors were genotyped for the above loci with sequence-specific primer PCR and sequence-specific oligonucleotide probe PCR.
<b>RESULTSb>The frequencies of HPA-la, -1b, HPA-2a, -2b, HPA-3a, -3b, HPA-4a, -4b, HPA-5a, -5b, HPA-6a, -6b, HPA-15a, -15b were 0.9974, 0.0026, 0.9456, 0.0544, 0.5417, 0.4583, 0.9983, 0.0017, 0.9889, 0.0111, 0.9903, 0.0097, 0.5434 and 0.4583, respectively. The HPA-7-14 and HPA-16 showed no heterozygosity as the b allele was not detected in such loci. The most common genotypic combination for HPA was HPA-(1,4,7-14,16,17) aa-2aa-3ab-5aa -6aa-15ab (0.1820). HLA-A2 (0.3070) and HLA-B13 (0.1361) demonstrated the highest frequencies at their respective loci.
<b>CONCLUSIONb>The HPA and HLA loci are highly polymorphic among ethnic Hans from Shandong. The distribution of HPA polymorphisms also shows a great ethnic and territorial difference. It is important to construct regional database for the genotypes of HPA and HLA loci for platelet donors.
Alleles ; Antigens, Human Platelet ; genetics ; Asian Continental Ancestry Group ; genetics ; statistics & numerical data ; Blood Donors ; China ; Female ; Gene Frequency ; Genetics, Population ; Genotype ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; Humans ; Linkage Disequilibrium ; Male ; Polymorphism, Genetic
2.Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients.
Jian-chun GUO ; Xiao-mei DENG ; Jing WU ; Yun-hao XUN ; Xiao-xiao HUANG ; Wei-wei WANG ; Wei-zhen SHI
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(5):539-543
<b>OBJECTIVEb>To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.
<b>METHODSb>Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared.
<b>RESULTSb>Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both).
<b>CONCLUSIONSb>Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.
Antiviral Agents ; therapeutic use ; Gene Frequency ; HLA-DQ alpha-Chains ; genetics ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Medicine, Chinese Traditional ; Polyethylene Glycols ; therapeutic use ; Polymorphism, Genetic ; Recombinant Proteins ; therapeutic use ; Remission Induction ; Yin Deficiency ; genetics
3.PD-1 expression in HBcAg-specific CD8+ T cells of adolescents with chronic HBV infection.
Jun-Ying ZHOU ; Dong-Fang ZHOU ; Jun-Qing LI
Chinese Journal of Hepatology 2013;21(1):27-32
<b>OBJECTIVEb>To investigate the differential expression of programmed death-1 (PD-1) in the hepatitis B core antigen (HBcAg)17-28-specific CD8+ T cell subsets of adolescent patients with chronic hepatitis B virus (HBV) infection during the immune tolerant phase and the immune clearance phase.
<b>METHODSb>A total of 105 patients between the ages of 12-28 years old (mean age 17.20+/-6.35) with chronic HBV infection and 15 healthy age-matched individuals were enrolled in the study. The patients were divided into two groups according to their current status in immune clearance phase (n = 55) or immune tolerant phase (n = 50), as determined by hepatic biopsy pathology. Flow cytometry was used to detect HLA-A2 type and PD-1 expression on peripheral blood mononuclear cells (PBMC) and HBcAg17-28-specific CD8+ T cells. PD-1 mRNA levels in PBMCs were measured by reverse transcription-polymerase chain reaction (RT-PCR). Independent samples t-test was used to compare means between the two groups, and one-way ANOVA was used to compare means among multiple groups. Pearson's correlation coefficient was used to assess the significance of correlation.
<b>RESULTSb>The frequency of HBcAg18-27-specific CD8+ T cells was significantly higher in the immune clearance phase group than in the immune tolerant phase group (t = 18.08, P less than 0.01), but the expression of PD-1 on the HBcAg18-27 specific CD8+ T cells was significantly lower in the immune clearance phase group than in the immune tolerant phase group (t = 4.72, P less than 0.01). A negative correlation existed between the frequency of HBcAg18-27-specific CD8+ T cells and PD-1 expression (r = -0.463, P less than 0.01). A positive correlation existed between HBV viral load and PD-1 expression on the HBcAg18-27-specific CD8+ T cells in chronic HBV infection patients (r = 0.882, P less than 0.01), and there was a negative correlation between PD-1 expression levels on HBcAg18-27-specific CD8+ T cells and hepatic tissue inflammation score (r = -0.76, P less than 0.01). PD-1 mRNA in PBMCs was significantly higher in the immune tolerant phase group than in the immune clearance phase group (t = 30.89, P less than 0.01).
<b>CONCLUSIONb>Up-regulated expression of PD-1 is associated with HBV-specific CD8+ T cells and may play a crucial role in inhibiting their function during the immune tolerance phase of chronic HBV infection in adolescents.
Adolescent ; CD8-Positive T-Lymphocytes ; metabolism ; HLA-A2 Antigen ; Hepatitis B Core Antigens ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; Humans ; Leukocytes, Mononuclear ; metabolism ; T-Lymphocyte Subsets ; metabolism
4.Relationship between HLA-A, B alleles and red blood cell parameters of patients with --(SEA/αα) subtype of α(0)-thalassemia of Han ethnic population of Wuzhou city.
Xiu-Qun CHEN ; Jun LI ; Yong-Lin CAI ; Chuan-Jie LI ; Yu-Yi MA ; De-Wang HUANG ; Hai-Feng LI ; Ai-Ying LU ; Min-Zhong TANG
Journal of Experimental Hematology 2013;21(3):688-691
This study was purposed to investigate the relationship between HLA-A, B allele polymorphisms and red blood cell parameters of patients with --(SEA/αα) subtype of α(0)-thalassemia in Han ethnic population of Wuzhou city. The HLA genetic polymorphisms were determined by polymerase chain reaction-sequence-based typing (PCR-SBT) in 57 patients with --(SEA/αα) subtype of α(0)-thalassemia of Han ethnic population in Wuzhou city, Guangxi province, China. Mean corpuscular volume (MCV), hemoglobin (Hb), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were detected by automatic blood analyzer system. HbA2 were detected by electrophoretic method. The statistical analysis was performed by ordinal polytomous logistic regression. The results showed that Hb and HbA2 levels were significantly lower in patients positive for HLA-A*33:03, B*15:01 or B*55:02, and were significantly higher in patients positive for B*15:02 (P < 0.05). It is concluded that several HLA alleles may be associated with Hb level of --(SEA/αα) subtype of α(0)-thalassemia of Han ethnic population in Wuzhou city. This result has the value for understanding phenotype-genotype relationships in thalassemia.
Adolescent
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Adult
;
Alleles
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Child
;
Child, Preschool
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China
;
epidemiology
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Erythrocytes
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cytology
;
Ethnic Groups
;
genetics
;
Female
;
Genotype
;
HLA-A Antigens
;
genetics
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HLA-B Antigens
;
genetics
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Hemoglobins, Abnormal
;
genetics
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Humans
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Male
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Middle Aged
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Young Adult
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alpha-Thalassemia
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blood
;
classification
;
epidemiology
;
genetics
5.Correlation of HLA-A, B, DRB1 genes with leukemia.
Ying DU ; Xiao-lan LIANG ; Qian LI ; Wen-jie WU ; Jian LIU ; Le-jing SUN ; Lu-gui QIU
Journal of Experimental Hematology 2013;21(2):285-288
This study was aimed to investigate the correlation between HLA gene distribution and allele frequency of the patients with leukemia. PCR-SSP technique was used to detect the HLA genotype of 2994 umbilical cord blood units from healthy newborns (as control), the detecting result of which was compared with HLA genotypes of 1246 patients with leukemia searched in our cord blood bank. The differences between two groups were compared and analyzed. The results indicated that as compared with the control group, the allele frequencies of HLA-B*56 (0.56%), B*70 (0.24%) obviously increased (RR = 2.2546, 6.2598, χ(2) = 5, 5.98, P < 0.05), while the allele frequencies of HLA-A*03 (3.45%), A*30 (4.86%), B*13 (8.75%), B44* (3.25%), B61* (5.70%), DRB1*07 (8.23%), DRB1*15 (14.21%) obviously decreased in patients with leukemia (RR = 0.5889, 0.7187, 0.7359, 0.5713, 0.7127, 0.6242, 0.7976, χ(2) = 19.23, 9.82, 14.33, 20.48, 11.99, 33.21, 11.56, P < 0.01). It is concluded that HLA-B*56, B*70 alleles seem to be characterized by the genetic susceptibility to leukemia and may be served as risk markers for leukemia occurrence, while the HLA-A*03, A*30, B*13, B*44, B*61, DRB1*07, DRB1*15 can be considered as genetic indicators for resistance of leukemia.
Adolescent
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Adult
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Alleles
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Case-Control Studies
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Child
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Child, Preschool
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Female
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Fetal Blood
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Gene Frequency
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Genotype
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HLA-A Antigens
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genetics
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HLA-B Antigens
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genetics
;
HLA-DRB1 Chains
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genetics
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Humans
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Infant, Newborn
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Leukemia
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genetics
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Middle Aged
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Young Adult
6.Incidence and risk factors for development of new-onset diabetes after kidney transplantation.
Yong Mong BEE ; Hong Chang TAN ; Tunn Lin TAY ; Terence Ys KEE ; Su Yen GOH ; Peng Chin KEK
Annals of the Academy of Medicine, Singapore 2011;40(4):160-167
<b>INTRODUCTIONb>New-onset diabetes after transplantation (NODAT) is an increasingly recognised metabolic complication of kidney transplantation that is associated with increased morbidity and mortality. This study aimed to determine the incidence of NODAT and identify risk factors for development of NODAT among kidney allograft recipients in a single centre.
<b>MATERIALS AND METHODSb>We retrospectively reviewed all kidney allograft recipients in our centre between 1998 and 2007. NODAT were determined using criteria as per American Diabetes Association guidelines. Logistic regression analyses were performed to identify predictors of NODAT.
<b>RESULTSb>Among 388 patients included in the analysis, NODAT was reported in 94 patients (24.2%) after a median follow-up time of 52.1 months. The cumulative incidence of NODAT was 15.8%, 22.8% and 24.5% at 1, 3, and 5 years following transplantation. Seven clinical factors were independent predictors of NODAT: older age, HLA B13 and B15 phenotypes, use of sirolimus, acute rejections, higher pre-transplant and post-transplant (day 1) plasma glucose levels. Patients with NODAT had poorer outcomes in both graft and patient survival.
<b>CONCLUSIONb>Our study demonstrates a significant risk and burden of NODAT in an Asian transplant population. Risk stratification and aggressive monitoring of blood glucose early post-transplantation is necessary to identify high-risk patients so that appropriate tailoring of immunosuppression and early institution of lifestyle modifications can be implemented.
Adult ; Blood Glucose ; analysis ; Diabetes Mellitus ; etiology ; genetics ; Female ; Graft Rejection ; complications ; HLA-B Antigens ; analysis ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Risk Factors
7.Allele and Haplotype Frequencies of Human Leukocyte Antigen-A, -B, and -DR Loci in Koreans: DNA Typing of 1,500 Cord Blood Units.
Dong Hee WHANG ; Yun Sun YANG ; Hye Kyung HONG
The Korean Journal of Laboratory Medicine 2008;28(6):465-474
BACKGROUND: The HLA system is known to be the most polymorphic genetic system in human, and HLA allele and haplotype distribution varies widely among different ethnic groups. This study was performed to examine the frequencies of HLA alleles and haplotypes in Koreans. METHODS: We examined HLA-A, -B, and -DR alleles at the serologic level in 1,500 cord blood units obtained from Koreans using the PCR-sequence specific oligonucleotide (SSO) method. Allele and haplotype frequencies were estimated by the maximum likelihood method using the computer program developed for the 11th International Histocompatibility Workshop. RESULTS: HLA alleles found in Koreans were 12 in A, 31 in B, and 13 in DR loci. Most frequent alleles with frequencies > or =10% in each locus in decreasing order of frequency were: A2, A24, A33, A11; B62; DR4, DR15, DR9, and DR13. Two-locus haplotypes with frequencies > or =0.1% were 104 A-B and 115 B-DR haplotypes, among which those with frequencies > or =1.0% showing significant positive linkage disequilibrium (P< or =0.001) were 21 A-B and 20 B-DR haplotypes. A total of 169 A-B-DR haplotypes with frequencies > or =0.1% were identified. The results were similar to those of a previous study in 1,600 Koreans, although some differences were noted in the distribution of some less frequent alleles or haplotypes with frequencies < or =0.5%. CONCLUSIONS: We provided the allele and haplotype frequencies of HLA-A, -B, and -DR in cord blood units of Korean ethnicity defined by a DNA typing method, which can be used as basic data on Koreans for organ transplantation and disease association studies.
Fetal Blood
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*Gene Frequency
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HLA-A Antigens/classification/*genetics
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HLA-B Antigens/classification/*genetics
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HLA-DR Antigens/classification/*genetics
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*Haplotypes
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Histocompatibility Testing
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Humans
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Korea
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Polymerase Chain Reaction
8.Expression and analysis of HLA-A, B and DRB1 genes in patients with chronic myelogenous leukemia in Guangdong area.
Li WEI ; Lu-Lu XIAO ; Xiang-Yuan WU ; Qu LIN ; Ming DONG ; Jing-Yun WEN ; Xiao-Kun MA ; Fei CHONG
Journal of Experimental Hematology 2008;16(4):915-918
To study the gene polymorphism of HLA-A, B, DRB1 alleles in patients with chronic myelogenous leukemia and to explore the correlation of HLA with chronic myelogenous leukemia, the polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO) was used to analyze the polymorphism of HLA-A, B, DRB1 alleles of 293 CML Patients and 406 randomized and synchronous blood donors (healthy and unrelated with patients) from Guangdong Han population. The results indicate that the gene frequency of HLA-A*24 in CML group was 15.53% lower than that of control group (22.09%, RR = 0.63, p = 0.005); the gene frequency of HLA-B*13 in CML group was 10.41% higher than that of control group (6.74%, RR = 1.68, p = 0.016). The gene frequency of HLA- DRB1*14 in CML group was 7.51% lower than that of control group (11.89%, RR = 0.58, p = 0.008). The differences were all statistically significant. It is concluded that the gene frequency of HLA-A*24, HLA- DRB1*14 in CML patients is significantly lower than normal people in Guangdong. The gene frequency of HLA-B*13 in CML patients is significantly higher than normal people in Guangdong. Further study is needed to make sure whether HLA-A*24 and HLA- DRB1*14 are protective gene markers for CML acquisition on Guangdong Chinese Han population and whether HLA-B*13 is a gene marker for CML susceptibility on this population.
Adolescent
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Adult
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Aged
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Blood Donors
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Child
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Child, Preschool
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China
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Female
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HLA-A Antigens
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genetics
;
metabolism
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HLA-A24 Antigen
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HLA-B Antigens
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genetics
;
metabolism
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HLA-B13 Antigen
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HLA-DR Antigens
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genetics
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metabolism
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HLA-DRB1 Chains
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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genetics
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immunology
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Male
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Middle Aged
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Young Adult
9.Human Leukocyte Antigen Typing Proficiency Surveys in Korea, 2005-2006.
Myeong Hee KIM ; Sung Eun CHOI ; Heung Bum OH
The Korean Journal of Laboratory Medicine 2007;27(6):442-450
BACKGROUND: To monitor the performance of histocompatibility testing laboratories, HLA proficiency survey in Korea has been conducted biannually since 1996. In this report, we summarized the results of the surveys performed in recent two years (2005-2006). METHODS: A total of four proficiency surveys were performed, in which 59-61 laboratories participated. Each survey included three tests for HLA class I (serology and DNA) and class II (DNA) typing and six tests for HLA crossmatch. RESULTS: The overall concordance of serologic typing was 98.9% (355/359) for HLA-A, 97.5% (350/ 359) for HLA-B, and 94.7% (337/356) for HLA-C. The antigens assigned correctly by less than 95% of the participating laboratories were A26 (93.8%), B38 (94.2%), Cw3/Cw10 (90.9%), Cw6 (94.4%), and Cw8 (74.3%). The overall concordance rates of DNA typing were 99.6% (533/535) for HLA-A, 99.8% (539/540) for HLA-B, and 100% (392/392) for HLA-C. Correct assignment of HLA-DRB1 and -DQB1 was reported by 99.2% (98.1-100%) and 96.7% (88.9-100%) for the generic level and 100% and 95.8% (75-100%) for the allelic level, respectively. On the average 3.8% (0-7.7%) of the total laboratories showed unacceptable results in the crossmatch tests. CONCLUSIONS: The rates of correct antigen identification and of unacceptable crossmatch were similar to those of previous surveys, which were considered satisfactory. The Korean proficiency survey program may have contributed to a high quality of HLA tests today and should be continued for further improvements of the tests tomorrow.
Alleles
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Data Collection
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HLA Antigens/*blood/genetics
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HLA-A Antigens/blood/genetics
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HLA-B Antigens/blood/genetics
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HLA-C Antigens/blood/genetics
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HLA-DQ Antigens/blood/genetics
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HLA-DR Antigens/blood/genetics
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Haplotypes
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Histocompatibility Testing/*standards
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Humans
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Korea
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Laboratories
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Quality Control
10.Genetic status of a AB chimeric blood group family.
Bao-Cheng YANG ; Qiong YU ; Yu-Qing SU ; Dan ZHOU ; Shi-Zheng JIN ; Qian LI ; Yan-Lian LIANG ; Zhi-Hui DENG
Journal of Experimental Hematology 2007;15(2):417-420
In order to study the genetic status of a rare chimeric family, some samples of A(3)B(3) family were identified by sequencing of ABO gene; flow-rSSO and PCR-SSP were used to detect loci of HLA-A, B, DRB1 genes, and multiplex amplifying with fluorescence-dye were performed for 16 short tandem repeat (STR) loci. The results indicated that two individuals from A(3)B(3) family contained more than two alleles at ABO gene, HLA-B, DRB1 and some STR loci. In conclusion, analysis of chimeric blood group by using genotyping techniques clearly demonstrating genetic status of this rare chimeric blood group promotes further elucidation of the existing state of specific genetic status.
ABO Blood-Group System
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genetics
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immunology
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Adult
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Chimerism
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Female
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Genotype
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HLA-A Antigens
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genetics
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HLA-B Antigens
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genetics
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HLA-DR Antigens
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genetics
;
HLA-DRB1 Chains
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Humans
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Male
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Pedigree
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Polymorphism, Genetic
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Tandem Repeat Sequences
;
genetics

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