• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4427-4433
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• 2013

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphisms have been shown to be associated with cervical cancer risk, but results have varied among different populations. In this study, the HLA-A, -B, and -DRB1 alleles among 100 southern Chinese women with cervical squamous cell carcinoma (SCC) were compared to 254 controls. Our results showed that $B^*51$:01:02 allele frequency was significantly higher in patients with SCC than in healthy controls ($P=3.17{\times}10^{-5}$, $P_c$=0.005, OR=26.7). Statistical analysis also revealed a significantly decreased frequency of $B^*51$:01:02 ($P=7.01{\times}10^{-4}$, $P_c$=0.03, OR=0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-$B^*51$:01:02 may confer susceptibility to SCC and HLA-$B^*51$:01:02 may contribute to resistance to the development of SCC in Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in cases and controls after multiple testing corrections, indicating the individual allele associations to be independent of the identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved with susceptibility for developing SCC.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.79-87
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• 1994

For the purpose of evaluating the human leukocyte antigen(HLA) disease-association with bipolar disorder, HLA class I and class II allelic frequencies were assessed in 37 bipolar patients and were compared to the data from normal population. HLA class 1 typing was performed with microlymphocytotoxicity method while class II(DRB1) genotyping with reverse dot blot hybridization and sandwich method. Statistical analysis consisted of relative risk, Haldane's modified relative risk, Fisher's exact test and Bonferoni's corrected P. The results were as follows : 1) Bipolar patients showed increased allelic frequency of HLA A3 which has statistical significance. 2) Allelic frequencies of HLA B7, B14 and B54 were higher, while those of B51 and B55 were lower in bipolar patients, but they were not statistically significant. 3) Both of increased frequencies of DR2 in bipolar patients and DR15 in normal controls had statistical significance. The results of the present study suggested that some of HLA allelic types might be associated with bipolar disorder. To clarify the genetic influence of HLA to bipolar disorder, we should do consecutive study of bipolar disorder with new information about HLA system including alleles.

• Translational and Clinical Pharmacology
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• v.25 no.2
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• pp.63-66
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• 2017

Allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are reportedly associated with the $HLA-B^{\star}58:01$ genotype. Three patients who developed SCARs after allopurinol administration were subjected to HLA-B genotyping and lymphocyte activation test (LAT) to evaluate genetic risk and to detect the causative agent, respectively. All three patients given allopurinol to treat gout were diagnosed with DRESS syndrome. Symptom onset commenced 7-24 days after drug exposure; the patients took allopurinol (100-200 mg/d) for 2-30 days. HLA-B genotyping was performed using a polymerase chain reaction (PCR)-sequence-based typing (SBT) method. All patients had a single $HLA-B^{\star}58:01$ allele: $HLA-B^{\star}13:02/^{\star}58:01$ (a 63-year-old male), $HLA-B^{\star}48:01/^{\star}58:01$ (a 71-year-old female), and $HLA-B^{\star}44:03/^{\star}58:01$ (a 22-year-old male). Only the last patient yielded a positive LAT result, confirming that allopurinol was the causative agent. These findings suggest that patients with $HLA-B^{\star}58:01$ may develop SCARs upon allopurinol administration. Therefore, HLA-B genotyping could be helpful in preventing serious problems attributable to allopurinol treatment, although PCR-SBT HLA-B genotyping is time consuming. A simple genotyping test is required in practice. LAT may help to identify a causative agent.

• Journal of Sasang Constitutional Medicine
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• v.13 no.1
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• pp.97-103
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• 2001

Purpose This study was designed co determine the possibility of HLA typing in the objeccification of constitution. Methods We selected 100 patients who showed Taeyang characteristics, and divided them into Soum-inclined group and Soyang-inclined group. HLA-A, B, DRBI typing was perfomed by ARMS-PCR and PCR-SSOP method. Results Taeyang characteristic group as a whole showed significant difference in A1, A11, B37, B70/71, DRBI*15,DRB1*14 alleles in comparison with normal control group. Soum-inclined group showed significant difference in All, B70/71, Soyang-inclined group in DRBl*15, hard drinker group in DRBl*15, DRBl*13, drink-rejecting group in All, B37, DRBl*7, DRB1*14 in comparison with normal control group. Conclusion : There were significant relations between constitutional information and HLA types.

• IMMUNE NETWORK
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• v.7 no.3
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• pp.149-157
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• 2007

Background: The microsatellites within human leukocyte antigen (HLA) region show considerable polymorphism and strong linkage disequilibrium (LD) with HLA alleles. These microsatellites have been used for genetic analysis including disease mapping to understand susceptibility to autoimmune and infectious diseases. Also, use of microsatellites has recently been proposed as an approach for identifying non-HLA markers within the HLA region that could function as transplantation determinants and for the selection of potential donors for transplantation. Methods: To analyse the frequency of five microsatellites in the Korean population, genotyping for polymorphisms at five microsatellites markers (BAT2, MIB, DQCAR, D6S105 and TNFd) within HLA region was performed on 143 healthy Korean controls. Results: The most frequent genotype shown in healthy Korean controls were BAT2 8 (153 bp, 42.7%), MIB 1 (326 bp, 40.6%), DQCAR 3 (188 bp, 38.5%), D6S105 7 (126 bp, 58.0%) and TNFd 3 (128 bp, 58.0%). And common two-loci haplotypes were found as MIB 1-HLA-B*62 (HF: 10.6%), MIB 6-HLA-B*44 (HF: 7.8%), DQCAR 3-HLA-DRB1*13 (HF: 8.5%), TNFd 5-HLA-B*62 (HF: 7.8%) and D6S105 7-HLA-A*02 (HF: 16.2%). Conclusion: These data might provide useful information on the microsatellites markers with HLA region in Korean population and be helpful in further defining the clinical impact of these microsatellites.

• The Journal of the Korean Society for Microbiology
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• v.19 no.1
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• pp.79-83
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• 1984

To determine the existence of anti-HLA antibodies finally in 220 human placental extracts to be proved negative antiserum by previous anti-HLA A,B,C antibody screening procedure, the present study was performed by fractionation of immunoglobulins using saturated ammonium sulfate and by simple batch method on DEAE cellulose. Thereafter using known 150 T-lymphocyte panels, complement-dependent microlymphocytotoxicity test was performed to observe the existence of anti-HLA antibodies and the degree of the antibody response of the concentrates. The following results were obtained: 1. Of total 141 placental sera concentrated 45 cases(31.9%) were showed significant anti-HLA A,B,C antibody response after concentration(Excellent, 19(13.5%), Good, 3(2.1%), Weak, 23(16.3%)). 2. Anti-HLA specificities of placental sera obtained after concentration were A2, A24, B13, B27, B44, B51, CN1, C7. 3. A new type C new-1 anti-HLA antibody that is only expressed in Korean people, was obtained. 4. 79 placental sera purrified by simple batch method using DEAE cellulose were showed negative anti-HLA antibody responses.

• Childhood Kidney Diseases
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• v.4 no.1
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• pp.33-39
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• 2000

Purpose: Our study was designed to investigate the association of MHC Class II (DR, DQ) allele with IgA nephropathy and its significance as a prognostic factor for progression to ESRD Material and Methods: 69 children with IgA nephropathy with normal renal function(serum creatinine $\leq$ 1.5mg/dL) was classified as group A and 70 patients who received renal transplantation due to IgA nephropathy were selected as group B. The HLA-DQB1 and HLA-DRB1 alleles were studied by polymerase chain reaction using sequence specific primers. We have compared the difference in alleles between these two groups and with normal control and also examined any possible effect of the MHC class II genes on the histopathological severity and prognosis of IgAN. Results: Mean age was $8.8{\pm}2.9$ years in group A and $35.0{\pm}15.5$ years in group B. Male to female ratio was 2.8:1 in group A and 2.5:1 in group B. There was a significantly higher frequency of HLA-$DQB1^*03\;and\;DQB1^*05$ in Group B. The frequency of HLA-$DQB1^*0302\;and\;^*05031$ allele had increasing tendency in Group B(P<0.05). HLA-$DRB1^*03\;and\;^*05$ were more common in Group B(P<0.05). HLA-$DRB1^*04$ allele was the most common DR alleles in both group, but there was no statistical significance. There were no significant correlation with MHC class 13 genes on the hjstopathological severity in Group A. Conclusion: In conclusion, $HLA-DQB1^*0302\;and\;HLA-DQB1^*05031 $ allele seemed to be more common in transplanted patients compared to group with normal renal function suggesting that this allele is associated with poor prognosis in IgAN. However larger studies and follow up are required to confirm this due to uncharacterized heterogeneity in etiopathogenesis of IgA nephropathy and possibly one or more than one gene may exert influence in determining susceptibility to the diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10299-10306
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• 2015

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.242-247
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• 2002

Background: Tumor necrosis factor-alpha (TNF-$\alpha$) is known to play an important role in various conditions such as inflammation, autoimmunity, apoptosis, insulin resistance and sleep induction. Five single nucleotide polymorphisms (SNPs) have been known to affect the transcriptional activities of TNF-$\alpha$: -1,031T/C, -863C/A, -857C/T, -308G/A and -238G/A. Methods: We have investigated 5 SNPs of the promoter region of TNF-$\alpha$ gene, the distribution of 5-locus TNF-$\alpha$ haplotypes, and their haplotypic associations with previously typed HLA-A, -B and -DRB1 loci in 107 healthy unrelated Koreans. TNF-$\alpha$ SNPs were typed using PCR-single-strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. Results: The allele frequencies of -1,031C, -863A, -857T, -308A, and-238A, which are known as the high-producer-type, were 19.3%, 15.9%, 14.0%, 5.9%, and 2.9%, respectively. The frequency of -308A allele, known to be associated with autoimmune diseases, was 5.9% in Koreans which was lower than Caucasians (14~17%) and somewhat higher than Japanese (1.7%). Five most common TNF-$\alpha$ haplotypes (-1,031/-863/-857/-308/-238) comprised over 95% of total haplotypes: TCCGG (58.4%), CACGG (14.8%), TCTGG (13.7%), TCCAG (5.3%), and CCCGA (3.1%). Strong positive associations (P<0.001) were observed between TCCGG and B62; between CACGG and B51, $DRB1^*0901$; between TCTGG and B35, B54, B59, $DRB1^*1201$; and between TCCAG and A33, B58, $DRB1^*0301$, $DRB1^*1302$. Five most common extended haplotypes (>3%) comprised around 16% of total haplotypes: A33-B58-TCCAG-$DRB1^*1302$, A24-B52-TCCGG-$DRB1^*1502$, A33-B44-TCCGG-$DRB1^*1302$, A24-B7-TCCGG-$DRB1^*0101$, and A11-B62-TCCGG-$DRB1^*0406$. The distribution of extended HLA and TNF-$\alpha$ haplotypes showed that most of HLA haplotypes were almost exclusively associated with particular TNF-$\alpha$ haplotypes. Conclusion: The results obtained in this study would be useful as basic data for anthropologic studies and disease association studies in Koreans.

• Clinical and Experimental Pediatrics
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• v.54 no.7
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• pp.313-315
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• 2011

Reactive arthritis comprises a subgroup within infection-associated arthritides in genetically susceptible hosts. Researchers and clinicians recognize two clinical forms of reactive arthritis which occurs after genitourinary tract infection and after gastrointestinal tract infection. Chlamydia infection has been implicated as the most common agent associated with post-venereal reactive arthritis. Studies have proposed Shigella infection, Salmonella infection, or Yersinia infection as the microorganisms responsible for the post-dysenteric form. The human leukocyte antigen (HLA)-B27 antigen is the best-known predisposing factor. We report a case of HLA-B27-associated reactive arthritis after Salmonella enteritis at Pusan National University hospital.