• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.548-553
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• 2010

목 적: IgA 신병증은 소아들의 만성 사구체 신염 중에서 가장 흔하게 일어나며, HLA유전자는 다양한 염증성 질환과 자가면역질환과 연관이 있어 왔다. 이 연구에서는 한국인에서 건강한 대조군과 IgA 신병증 환자군을 비교하여 IgA 신병증 발생 감수성 및 병리, 임상 양상과 $HLA-G$ 유전자의 SNP와의 연관성에 관해 알아보고자 하였다. 방 법: 소아 IgA 신병증을 앓고 있는 174명의 환자군과 438명의 정상 대조군에서 $HLA-G$ 유전자의 promoter SNP (rs1736936과 rs2735022)를 분석하고 비교하였다. 또한 IgA 신병증 환자들을 단백뇨($4mg/m^2/hour$ 이하군과 이상군)의 유무, 족세포 돌기의 소실 유무, 간질의 섬유화 및 세뇨관 위축이나 미만성 사구체 경화와 같은 병리학적 소견상 진행성 질환의 표지자유무에 따라 하위그룹으로 나누어 비교하였다. 결 과: IgA 신병증 환자군과 정상 대조군 간의 HLA-G에서의 SNP (rs1736936과 rs2735022) 빈도에 대한 유의한 차이는 발견되지 않았다. 또한 단백뇨의 유무, 족세포 돌기의 소실 유무, 질환의 병리학적 진행 정도을 의미하는 표지자의 유무와 SNP사이에서도 유의한 연관성을 보이지는 않았다. 그러나, 일체 배형으로서 rs1736936과 rs2735022는 소아 IgA 신병증을 일으키는 감수성에 대해 통계학적으로 유의한 연관성을 나타내었다(haplotype T/C: dominant model OR 1.71, 95% CI 1.00-2.92, $P$=0.049; haplotype C/T: recessive model OR 0.54, 95% CI 0.31-0.94, $P$=0.030). 결 론: 이번 연구에서 $HLA-G$ 유전자의 SNP 중 rs1736936와 rs2735022로 이루어진 일체배형과 IgA 신병증의 발생간에 유의한 관계를 관찰하였으며, IgA 신병증 환자들의 단백뇨 발생 유무, 족세포 돌기의 소실 유무 및 질병 진행 정도로 구분된 하위그룹과 후보 SNP들간의 유의한 관계는 확인할 수 없었다.

• Genomics & Informatics
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• 제13권4호
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• pp.126-131
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• 2015

Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The $HLA-DRB1^*04:05-HLA-DQB1^*04:01$ haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at $HLA-DR{\beta}1$ position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI, 1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

• 대한임상검사과학회지
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• 제37권3호
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• pp.216-219
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• 2005

We report a case of narcolepsy. A 25-year-old man has had excessive daytime sleepiness of about 10 years durations. He awakens daily feeling exhausted and continually falls asleep during the day while engaged in such situation like reading and watching television. He has exhibited cataplexy, a sudden loss of muscular tone, brought on by emotion, usually laughter. Polysomnogram revealed increased sleep stage 1, 2 and decreased deep sleep. Multiple sleep latency test (MSLT) showed that sleep latency was 1.33 minutes and there were 3 noted sleep onset rapid eye movement (SOREM) on 5 trials. The epworth sleepiness scale (ESS) was 17/24. Typing of HLA haplotype that was positive for the $DQB1^{\ast}0602$ allele, and hypocretin-1 (orexin A) could not be detected in cerebrospinal fluid (CSF). Brain MRI showed normal image. We diagnosed his case as narcolepsy based on history of cataplexy, and three occurances of SOREM, and positive of HLA haplotype.

• IMMUNE NETWORK
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• 제2권4호
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• pp.248-255
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• 2002

Background: TAP1 and TAP2 are two ABC transporter genes located within the class II region of the human MHC. Their protein products form a heterodimer whose function is to transport peptides from the cytoplasm into the endoplasmic reticulum. This study was performed to examine the polymorphism of TAP genes and the distribution of HLA-TAP haplotypes in the Korean population through family analysis. Methods: The subjects used in this study were 50 healthy Korean families consisting of 233 individuals. TAP1 (codons 333 and 637) and TAP2 (codons 379, 565, 577, 651, 665, and 687) typings were carried out by the PCR-restriction fragment length polymorphism (RFLP) method. HLA-DRB1 and DQB1 genotyping results from a previous study were used for HLA-TAP haplotype analysis. Results: The number (gene frequency) of TAP1 and TAP2 alleles detected were 3 for TAP1 (A 81.5%, B 17.0%, and C 1.5%) and 8 for TAP2 (A1 32.0%, A2 12.5%, B 34.0%, Bky2 6.5%, C 7.0%, D 3.0%, E 4.5%, and G 0.5%). Eleven TAP1-TAP2 haplotypes were observed with $frequency{\geq}1%$, among which 4 haplotypes (A-B, B-A1, A-Bky2, and C-E) showed weak but significant positive linkage disequilibrium (P<0.05). When DRB1-DQB1 haplotypes were extended to TAP1 and TAP2 loci, much diversification of haplotypes was observed: 19 different DRB1-DQB1 haplotypes formed 58 different haplotypes extended to TAP1 and TAP2 loci. These results add more evidence to the view that recombination hotspot is present within and around TAP gene region. Conclusion: The allele frequencies of TAP1 and TAP2 genes and the distribution of TAP1-TAP2 and HLA-TAP haplotypes were studied in Koreans based on a family study.

• 대한미생물학회지
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• 제21권2호
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• pp.171-179
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• 1986

The HLA class II region encodes a series of polymorphic glycoproteins that form cell surface heterodimers each consisting of one $\alpha$ and one $\beta$ chain. Thess class II molecules are encoded by genes clustered within three loci. DP, DQ, and DR are functfonally implicated as regulatory signals in intercellular communication during the immune resposes. The phenotypic hallmark of the HLA complex is a high degree of structural and functional polymorphism. Detailed analysis. of such polymorphisms should aid in understanding the molecular basis for associations between HLA and diseases. We have used techniques of restriction enzyme fragment analysis by Southern blotting to investigate polymorphisms associated with DQ $\beta$ class II genes on haplotypes expressing the HLA-DR4 and -DQw3 specificities. The endonucleases Hind III and Bam HI were used to identify a specific DQ $\beta$ genomic polymorphism that precisely corrresponds with the reactivity of a monoclonal antibody A-10-83, previously shown to define a serologic split of DQw3. This study identifies two allelic DQ va. riants. DQw3.1 and DQw3.2. We used these specific genotypic markers to investigate the genomic basis of the association of DR4 with insulin-dependent diabetes mellitus(IDDM) and seropositive juvenile rheumatoid arthritis(JRA). The DR4 positive IDDM demonstrate the predominant expression of DQw3.2 and the very rare expression of DQw3.l. However, in haplotype matched siblings from two IDDM families, all of the DR4 positive siblings display a IDDM-associated DQw3.2 allele. Thus, both affected and healthy individuals can carry the same haplotypes and genomic markers, demonstrating that thess specific allelic variants are genetic elements that indicate a increased risk of IDDM but are not in fact disease specific. We contrasted this result with a similar analysis of patients with another DR4-associated disease, JRA. In contrast to the preponderance of the DQw3.2 allele in IDDM, the JRA patients expressed either the DQw3.1 or the DQw3.2 allele and sometimes both, without apparent association with disease expession. The different genomic markers reported here within HLA-DQ region potentially an analysis of HLA-associated function and disease susceptibility.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2491-2497
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• 2016

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; p< $3.5{\times}10^{-4}$), DRB1*14-DQB1*0501 (OR=6.51; p<0.039) and A*11-B*07 (OR=3.95; p<0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; p<0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ${\beta}9$ and ${\beta}37$ and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.

• BMB Reports
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• 제39권4호
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• pp.418-425
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• 2006

A human bacterial artificial chromosome (BAC) library was constructed with high molecular weight DNA extracted from the blood of a male Korean. This Korean BAC library contains 100,224 clones of insert size ranging from 70 to 150 kb, with an average size of 86 kb, corresponding to a 2.9-fold redundancy of the genome. The average insert size was determined from 288 randomly selected BAC clones that were well distributed among all the chromosomes. We developed a pooling system and three-step PCR screen for the Korean BAC library to isolate desired BAC clones, and we confirmed its utility using primer pairs designed for one of the clones. The Korean BAC library and screening pools will allow PCR-based screening of the Korean genome for any gene of interest. We also determined the allele types of HLA-DRA and HLA-DRB3 of clone KB55453, located in the HLA class II region on chromosome 6p21.3. The HLA-DRA and DRB3 genes in this clone were identified as the DRA*010202 and DRB3*01010201 types, respectively. The haplotype found in this library will provide useful information in future human disease studies.

• BMB Reports
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• 제31권2호
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• pp.111-116
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• 1998

HLA-DR4 is the dominant allele of MHC class II genes in Koreans. In particular, the $DRB1^*0405$ subtype has been reported to be almost exclusively expressed in Far East Asians, and has also been observed to be strongly associated with rheumatoid arthritis in Koreans and the Japanese. Identification of this specific allele has been mainly performed by PCR-based methods, which is often time consuming, costly, and involves tedious procedures such as the isolation of genomic DNA, PCR, and gel electrophoresis. To develop a more convenient tool for screening vast amounts of samples as well as to generate reagents which might also be used in other applications, in this study, antibodies were produced against this specific HLA subtype. By PCR, an allelespecific region covering the ${\beta}1$ domain of $DRB1^*0405$ was amplified and recombinantly expressed in E.coli. Immunization of Lewis rats with the purified protein yielded an allele specific antiserum. Western blot analysis showed the selective detection of the HLA-DR ${\beta}-chain$. Using this antiserum, established cell lines and peripheral blood lymphocytes were analyzed on their HLA haplotype by fluorescence activated flow cytometry. These novel antibodies will provide a powerful tool in the detection and investigation of DR4 alleles.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1247-1251
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• 2012

Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.

• IMMUNE NETWORK
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• 제2권4호
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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.