Biomedical subjects

H Han

Publications and source records attributed to H Han.

At least 19 recordsLinked to original sources

PubMed2001

Oxygen-sensing microdialysis probe for in vivo use.

Electrochemical conditions were optimized to allow the metal tube used for the shaft of commercial microdialysis (MD) probes to be coated with gold. In in vitro tests with phosphate-buffered Ringer's solution using double differential pulse amperometry (DDPA), the gold-coated shafts were capable of specifically measuring the reduction of oxygen and the oxidation of ascorbic acid in the presence of high concentrations of potentially interfering endogenous substances. By using fixed-potential amperometry (FPA), the gold-plated shaft also measured oxygen with minimal interference from high concentrations of potentially interfering endogenous substances. Concentric design MD probes were constructed that used a metal shaft (O.D = 0.4 mm), fused silica inlet and outlet tubes, and a 1.5 mm dialyzing membrane (O.D = 0.2 mm). A 0.5-0.7 mm gold collar was electroplated onto the metal shaft approximately 0.5 mm above the dialyzing membrane. The nongold outer surface of the MD probe was coated with an insulating polymer. In vivo tests demonstrated that DDPA was not suitable for use with this gold microdialyzing electrode (GMDE). However, brain oxygen levels were satisfactorily measured using FPA. In urethane-anesthetized rats, the reduction current to oxygen in the striatum was increased by brief (1 min) inhalation of O2 or CO2 and decreased by inhalation of N2. Transient application of noxious stimuli (foot pinch) increased cerebral O2, whereas bilateral carotid artery occlusion and death decreased striatal O2. The responses of the GMDE were indistinguishable from the reduction current simultaneously measured from a conventional carbon fiber electrode implanted adjacent to the gold-plated area of the MD shaft. Basal levels of striatal O(2) were 20 +/- 5 microM (n = 4) for the GMDE and 30 +/- 11 microM (n = 3) for the carbon fiber. The GMDE was robust and could be used for at least three animals. This technique can be used to provide information about the oxygen status of the tissue adjacent to the dialyzing membrane without the need for implantation of an additional electrode.

Animals↗

PubMed2001

Regulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells by glucocorticoids: evidence for nongenomic as well as genomic mechanisms.

We have investigated the nongenomic as well as the genomic effects of glucocorticoids on phosphate (Pi) uptake in primary rabbit renal proximal tubule cells (PTCs) and have defined the involved signaling pathways. In the present study, cortisol-BSA (cortisol-BSA) (>10(-9) M, 30 min) was found to inhibit Pi uptake in a time- and concentration-dependent manner. However, progesterone-BSA (P(4)-BSA), 17ss-estradiol-BSA (E(2)-BSA), testosterone-BSA (T(4)-BSA), aldosterone, P(4), E(2), and T(4) (10(-9) M, 1 h) had no effect on Pi uptake. In addition, cortisol-BSA (10(-9) M) did not affect either Na(+) uptake or alpha-methylglucopyranoside (alpha-MG) uptake. The cortisol-BSA-induced inhibition of Pi uptake was associated with a decrease in the V(max) for Pi uptake, rather than the K(m). The inhibitory effect of cortisol-BSA was not blocked either by actinomycin D (an inhibitor of transcription), cycloheximide (an inhibitor of translation), or classical glucocorticoid receptor antagonists (RU 486 or P(4)). The cortisol-BSA-induced inhibition of Pi uptake was blocked by two phospholipase C (PLC) inhibitors (neomycin or U73122), and two protein kinase C (PKC) inhibitors (staurosporine or bisindolylmaleimide I) but not by two adenylate cyclase/protein kinase A inhibitors [SQ 22536 (an adenylate cyclase inhibitor) or myristoylated protein kinase A inhibitor amide 14-22]. Furthermore, cortisol-BSA promoted the translocation of PKC from the cytosolic fraction to the membrane fraction, while having no effect on the activity of adenylate cyclase. Our observations may thus be interpreted as indicating that cortisol does indeed inhibit renal Pi uptake via a nongenomic mechanism, which involves the PLC/PKC pathway.

Animals↗

PubMed2000

High-performance polyethylene glycol-coated solid-phase microextraction fibers using sol-gel technology.

The sol-gel method is applied for the preparation of solid-phase microextraction (SPME) fibers. An electron microscopy experiment suggested a porous structure for Superox-4 (polyethylene glycol, PEG) coating. SPME-GC analyses provided evidence that the sol-gel fibers have some advantages, such as high velocities of mass transfer, efficient extraction rates. high thermal stability, long life span, and spacious range of application for both polar and non-polar analytes. Efficient SPME-GC analyses of benzene-toluene-ethylbenzene-xylenes, phenols, phthalic diesters, naphthalene congeners and pesticides were achieved using sol-gel-coated PEG fibers.

Chromatography, Gas↗

PubMed2000

Expression of various multidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells.

Multidrug resistance-associated protein (MRP) actively transports a broad range of anionic compounds out of the cell. To date, six different homologues of MRP (i.e. MRP1-MRP6) have been identified. The current study examines the expression of the various MRP homologues in both primary cultured bovine brain microvessel endothelial cells (BBMEC) and the capillary-enriched fraction from bovine brain homogenates. RT-PCR analysis demonstrated the presence of MRP1, MRP4, MRP5 and MRP6 in both BBMEC and the capillary-enriched fractions of brain homogenates. While low levels of MRP3 were detected in the BBMEC, it was not observed in the capillary-enriched fraction. In addition, RT-PCR and Western blot studies indicated an absence of MRP2 expression in both blood-brain barrier preparations. The presence of several different MRP homologues in the brain microvessel endothelial cells may be important in controlling the permeability of the blood-brain barrier to organic anions.

ATP-Binding Cassette Transporters↗

PubMed2000

Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the presence of N,N'-bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide, a G-quadruplex-interactive ligand.

N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER), a perylene derivative, is a very potent and selective G-quadruplex DNA-interactive agent. It has been shown to inhibit DNA polymerase and telomerase by stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we have demonstrated that this small molecule greatly accelerates the assembly of G-quadruplex structures in a cell-free system. In this report, we present data demonstrating that PIPER prevents the unwinding of G-quadruplex structures by yeast Sgs1 helicase. Sgs1 belongs to the RecQ DNA helicase family whose members include other G-quadruplex DNA unwinding helicases, such as human Bloom's syndrome and human Werner's syndrome helicases. PIPER specifically prevents the unwinding of G-quadruplex DNA but not duplex DNA by Sgs1. Competition experiments indicate that this inhibitory activity is due to the interaction of PIPER with G-quadruplex structures rather than the helicase itself. These results combined with previous studies suggest a possible mechanism of action for these G-quadruplex-interactive agents inside cells: they might induce G-quadruplex formation in G-rich regions on genomic DNA, stabilize these structures, and prevent them from being cleared by enzymes such as helicases. The G-quadruplex structures may, in turn, disrupt some critical cellular events such as DNA replication, transcription regulation, and telomere maintenance.

Anthracenes↗

PubMed2000

Molecular phylogenetic study of the tribe Trypetini (Diptera: Tephritidae), using mitochondrial 16S ribosomal DNA sequences.

Monophyly and intratribal relationships of the tribe Trypetini were tested using mitochondrial 16S ribosomal RNA gene from 16 species of Trypetini, six tephritid outgroups, and two non-tephritid outgroups. The number of aligned sites was 1279 bp, but 1165 bp were used for analysis after excluding sites with missing data or gaps. Among these 1165 sites, 447 sites were variable and 305 were informative for parsimony analysis. Phylogenetic information was extracted from this data set using neighbor-joining and maximum parsimony methods and compared to a phylogenetic hypothesis proposed from the morphological literature. My molecular data suggest: (1) monophyly of the tribe Trypetini; (2) monophyly of the Chetostoma group; (3) monophyly of the Trypeta group; and (4) non-monophyletic nature of the previous concept of Hemilea. I suggest that more sensitive genetic markers with less A+T bias are needed to bring about finer resolution within the tribe Trypetini, and additional tephritid lineages should be sampled to identify the sister-group relationship of the tribe Trypetini.

Journal Article↗

PubMed2000

Cloning and characterization of the 5'-flanking region for the mouse phospholipase C-delta1 gene.

To date, little is known about the molecular mechanisms controlling the regulation of phospholipase C-delta1 (PLC-delta1) gene expression. To understand the mechanisms responsible for the regulation of PLC-delta1 gene expression, the 5'-flanking region of the mouse PLC-delta1 gene was isolated from a mouse genomic DNA library. Primer extension analysis revealed that there is a single transcriptional start site located at 127 bases upstream from the translation start codon in the mouse PLC-delta1 gene. DNA sequence analysis showed that the sequence around the transcriptional start site is very GC-rich and has no TATA or CAAT boxes. Transient expression of a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the 160-base-pair region from -622 to -462 upstream of the transcriptional start site includes a positive cis-acting element(s) for the efficient expression of the PLC-delta1 gene. Gel retardation analysis suggests that multiple transcription factors bind to separate sites on the promoter region. Based on these results, our study suggests that the minimal essential region located at -622 to +70 is fully sufficient to confer high-level transcriptional activity and contains high-affinity binding elements for multiple transcription factors.

Animals↗

PubMed2000

Overexpression of rapsyn modifies the intracellular trafficking of acetylcholine receptors.

Rapsyn is a protein that interacts with the cytoplasmic face of the nicotinic acetylcholine receptors (AChR) to cluster them within postsynaptic membrane of muscle. Here we show that intracellular AChRs are also affected by rapsyn. When rapsyn was co-transfected with AChR into QT-6 fibroblasts, (125)I-alpha-bungarotoxin binding indicated a reduction in the fraction of AChRs expressed on the cell surface, compared to cells expressing AChRs alone. Double fluorescent labeling showed that intracellular AChRs accumulated in patches at the cell periphery, beneath rapsyn-associated cell surface AChR clusters. These patches were observed even when cells were grown in medium containing excess unlabelled alpha-bungarotoxin to mask internalized AChRs, suggesting that they arose from hindered trafficking of newly formed AChRs to the cell surface. Similarly, in the muscle cell line, C2, overexpression of rapsyn resulted in the co-localization of aggregates of intracellular alpha-bungarotoxin binding sites with rapsyn beneath cell surface AChR microaggregates. The results indicate that rapsyn can modify the trafficking of AChRs within the cell and suggest a role in selectively targeting newly synthesized intracellular AChRs to the postsynaptic membrane.

Animals↗

PubMed2000

Human cytomegalovirus gene products US3 and US6 down-regulate trophoblast class I MHC molecules.

The epidemiological correlation between human CMV (HCMV) infection and spontaneous fetal loss has been suggested, but the underlying mechanism is not well understood. Fetal cytotrophoblasts, which are in direct contact with the maternal immune system in the uterus during pregnancy, do not express HLA-A and HLA-B, but express the nonclassical class I HLA-G and HLA-C. It has been shown that both HLA-G and HLA-C are capable of inhibiting NK-mediated cell lysis. In our present study, using human trophoblast cell lines as well as other cell lines stably transfected with the human class I genes, we have demonstrated that HCMV US3 and US6 down-regulate the cell-surface expression of both HLA-G and HLA-C by two different mechanisms. HCMV US3 physically associates with both trophoblast class I MHC species, retaining them in the endoplasmic reticulum. In contrast, HCMV US6 inhibits peptide transport by TAP and thus specifically the intracellular trafficking of class I molecules. Therefore, these findings suggest for the first time a possible molecular mechanism underlying HCMV-related spontaneous pregnancy loss.

3T3 Cells↗

PubMed2000

Association of HLA with Vogt-Koyanagi-Harada syndrome in Koreans.

PURPOSE: To study the distribution of human leukocyte antigen HLA-A/B antigens and HLA-DR/-DQ/-DP alleles and to investigate the immunogenetic background of Korean patients with Vogt-Koyanagi-Harada (VKH) syndrome and clinical course with different types of HLA. METHODS: Human leukocyte antigen typings were performed in 18 Korean patients with VKH syndrome and in 128 healthy control subjects. HLA-A/B loci serologic typing was performed according to the standard microlymphocytotoxicity technique. DNA was extracted through the salting out method, and HLA-DR phenotyping and HLA-DR4, HLA-DQ, and HLA-DP subtyping were performed with the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. RESULTS: Among HLA-A/B antigens typed by the standard microlymphocytotoxicity method, the frequencies of HLA-A31 (RR = 6.1, P<1x10(-2)) and HLA-B55 (RR = 15.8, P<.05) were significantly increased in the patient group compared with the control group. Among HLA-DR/-DQ/-DP alleles subtyped by DNA methods, the frequencies of HLA-DRB1*04 (RR = 45.1, P<1x10(-7)) and HLA-DRB1*07 (RR = 3.2, P<.05) were significantly increased. However, significant decreases in HLA-DRB1*08 (RR = .1, P<.05), HLA-DRB1*13 (RR = .1, P<.05), and HLA-DRB1*14 (RR = .1, P<.05) frequencies were observed. The result of HLA-DR, HLA-DQ, and HLA-DP subtyping showed the significant increase in DRB1*0405 (RR = 45.1, P<1x10(-7)), DQA1*0302 (RR = 12.0, P<1x10(-4)), DQB1*0303 (RR = 5.0, P<1x10(-2)), DQB1*0401 (RR = 18.9, P<1x 10-6), and DPB1*0501 (RR = 3.8, P<.05). However, significant decreases in DQA1*0101 (RR = .1, P< .05), DQA10102 (RR = .1, P<1x10(-2)), DQA1*0103 (RR = .1, P<.05), DQA1*0501 (RR = .1, P<1x10(-2)), DQB1*0301 (RR = .1, P<.05), DQB1*0601 (RR = .1, P<.05), DPB1*0201 (RR = .3, P<.05), and DPB1*0401 (RR = .1, P<.05) frequencies were also observed. In patients with DRB1*0405 itself or HLA-DRB1*0405-DQA1*0302-DQB1*0401 haplotype, a reduction in visual acuity and ocular complications was common. CONCLUSIONS: These results suggest that HLA-DRB1*0405 itself or HLA-DRB1*0405-DQA1*0302-DQB1*0401 haplotype is greatly increased and may play the most important role in the development and the clinical course of VKH syndrome in Korean patients.

Alleles↗

PubMed2000

G-quadruplexes as targets for drug design.

G-quadruplexes are a family of secondary DNA structures formed in the presence of monovalent cations that consist of four-stranded structures in which Hoogsteen base-pairing stabilizes G-tetrad structures. These structures are proposed to exist in vivo, although direct confirmatory evidence is lacking. Guanine-rich regions of DNA capable of forming G-quadruplex structures are found in a variety of chromosomal regions, including telomeres and promoter regions of DNA. In this review, we describe the design of three separate groups of G-quadruplex-interactive compounds and their interaction with G-quadruplex DNA. Using the first group of compounds (anthraquinones), we describe experiments that provide the proof of concept that a G-quadruplex is required for inhibition of telomerase. Using the second group of compounds (perylenes), we describe the structure of a G-quadruplex-ligand complex and its effect on the dynamics of formation and enzymatic unwinding of the quadruplex. For the third group of compounds (porphyrins), we describe the experiments that relate the biological effects to their interactions with G-quadruplexes.

Base Sequence↗

PubMed2000

G-quadruplex DNA: a potential target for anti-cancer drug design.

In addition to the familiar duplex DNA, certain DNA sequences can fold into secondary structures that are four-stranded; because they are made up of guanine (G) bases, such structures are called G-quadruplexes. Considerable circumstantial evidence suggests that these structures can exist in vivo in specific regions of the genome including the telomeric ends of chromosomes and oncogene regulatory regions. Recent studies have demonstrated that small molecules can facilitate the formation of, and stabilize, G-quadruplexes. The possible role of G-quadruplex-interactive compounds as pharmacologically important molecules is explored in this article.

Animals↗

PubMed2000

Distribution of seven polymorphic markers and haplotypes within the human TNF gene cluster in Koreans.

We examined the distribution of polymorphic elements within the tumor necrosis factor (TNF) gene cluster in 133 normals and in 20 Korean families and compared our data with the results of Caucasians. The genotypes that are shown frequently are TNF a6 (33.8%), TNF b5 (46.6%), TNF c1 (79.3%), TNF d3 (34.6%), TNF e3 (86.5%), TNFB*2 (51.5%), and TNF(-308) A (91.4%). In comparison, TNFa 6 (33.8%), TNFa 13 (4.1%), TNFb 5 (46.6%), TNFd 1 (7.5%), TNFd 3 (34.6%), TNFe 3 (86.5%), TNFe 4 (6.8%), and TNF(-308) A (91.3%) were found more frequently in Koreans than Caucasians (p < 0.01). TNFa 14, TNFa 15, TNFd 8, and TNFe 4 alleles were found only in Korean controls. However, TNFb 6 and TNFb 7 alleles were not found in this study. From the TNF gene of TNFa, TNFb, TNFc, TNFn, TNF(-308), TNFd, and TNFe, 49 different TNF haplotypes were found in 20 Korean families. These data suggest that the TNF microsatellite haplotypes constitute a highly polymorphic system and that will provide useful information on the association between the TNF marker and the immune disease.

Alleles↗

PubMed2000

MICA 5.1 allele is a susceptibility marker for psoriasis in the Korean population.

In order to investigate the possibility that the MICA gene is involved in the pathogenesis of psoriasis, microsatellite polymorphism in the transmembrane region of MICA was studied in 138 Korean patients with psoriasis and compared with 126 healthy controls. The MICA 5.1 microsatellite allele, consisting of 5.1 repetitions of GCT/AGC, showed significantly higher frequencies in all patients and in patients with type I psoriasis than in the controls. HLA-A30-B13-Cw*0602-MICA 5.1 and A1-B37-Cw*0602-MICA 5.1 were found to be an extended haplotype associated with psoriasis. Our results suggest that the MICA 5.1 allele might be a genetic marker related to the early onset of psoriasis and play a secondary role to the HLA-Cw*0602 gene or an unknown causative gene closely linked to HLA-Cw*0602 in the genetic susceptibility to psoriasis.

Alleles↗

PubMed2000

Interleukin-18 and the costimulatory molecule B7-1 have a synergistic anti-tumor effect on murine melanoma; implication of combined immunotherapy for poorly immunogenic malignancy.

Interleukin-18 has been described recently as a cytokine secreted primarily by Kupffer cells. Furthermore, it has been shown that it has significant anti-tumor effects, which are mediated by T cells and natural killer cells, in a manner similar to interleukin-12. Here, we report the evaluation of the effects of the systemic administration of interleukin-18 in combination with B7-1 (CD80) expressed on tumor cells [interleukin-18 + B7-1] on the growth of murine B16 melanoma in vivo. After the subcutaneous inoculation of B16 melanoma, B16 tumors grew progressively in immunocompetent syngeneic C57BL/6 mice. Mice treated with either interleukin-18 or immunized with B7-1-transduced B16 did not demonstrate significant anti-tumor effect. The combination of the two treatments, however, resulted in dramatic suppression of melanoma formation, tumor growth, and a significant improvement in survival. Inhibitory effects of [interleukin-18 + B7-1] on lung metastasis in mice were also detected. Additionally, mice treated with [interleukin-18 + B7-1] showed an increase of natural killer cytotoxicity and interferon-gamma production in vivo. Unlike [interleukin-18 + B7-1], [interleukin-12 + B7-1] did not have a strong anti-tumor effect against B16 melanoma. Histologic characterization after the [interleukin-18 + B7-1] treatment confirmed the infiltration of natural killer cells into the tumor, suggesting that natural killer cells may be involved in the [interleukin-18 + B7-1]-induced anti-tumor effect. This finding was confirmed by showing that depletion of NK1.1+ cells before immunization inhibits the [interleukin-18 + B7-1]-induced anti-tumor effect. Depletion of CD3+ cells in vivo also decreased the anti-tumor effect of [interleukin-18 + B7-1], suggesting the importance of CD3+ T cells. Collectively, combination with interleukin-18 and B7-1 expression has synergistic anti-tumor effects against B16 murine melanoma.

Animals↗

PubMed2000

The association of psoriasis with human leukocyte antigens in Korean population and the influence of age of onset and sex.

To identify HLA markers that may contribute to the genetic susceptibility of Koreans to psoriasis, we studied 84 psoriasis patients, with serologic HLA types of A, B, and genotypes of HLA-Cw, DRB1, DQA1, DQB1, DPB1 alleles. The distribution of HLA markers and the associated haplotypes were analyzed according to age and sex. HLA-Cw*0602 showed the strongest association with psoriasis (relative risk = 36.0, p < 10-8, Pc < 8 x 10-7). The frequencies of A1 (relative risk = 17.0, p < 9 x 10-7, Pc < 7 x 10-5), A30 (relative risk = 5.5, p < 2 x 10-5, Pc < 0.001), B13 (relative risk = 5.6, p < 4 x 10-6, Pc < 3 x 10-4), B37 (relative risk = 30.3, p < 7 x 10-7, Pc < 6 x 10-5), DRB1*07 (relative risk = 5.9, p < 2 x 10-6, Pc < 8 x 10-5), DRB1*10 (relative risk = 26.4, p < 4 x 10-6, Pc < 3 x 10-4), DQA1*02 (relative risk = 6.2, p < 5 x 10-7, Pc < 4 x 10-4), DQB1*02 (relative risk = 2.5, p < 0.005, Pc = ns) and DPB1*1701 (relative risk = 24.6, p < 9 x 10-6, Pc < 7 x 10-4) were also significantly increased in Korean psoriasis patients. Type I and type II psoriasis were subdivided into groups of below and above 30 y of age, because of the significant difference found in HLA-Cw*0602 phenotype frequency between the two groups (83.9% vs. 54.5%, p < 0. 009). In addition to HLA-Cw*0602, the frequencies of B37 and DPB1*1701 were significantly higher in type I as opposed to type II psoriasis. HLA-A30-B13-Cw*0602-DRB1*07-DQA1* 02-DQB1*02 was identified as a high risk haplotype. This was particularly true at an early age in the female. HLA-A33-B44-Cw*1401-DRB1*13-DQA1* 01-DQB1*06-DPB1*0401 was defined as a protective haplotype for psoriasis. The extended haplotype HLA-A1-B37-Cw*0602-DRB1*10-DQA1*01-DQB1*05 was discovered to be a high-risk factor in Koreans. To summarize, this study demonstrates the differential association of HLA according to sex, and identifies a newly found high-risk haplotype and a protective haplotype in Korean psoriasis patients.

Age of Onset↗

PubMed2000

Determinants of plasma total homocysteine levels in Korean chronic renal transplant recipients.

OBJECTIVE: Study the determinants of plasma total homocysteine (tHcy) levels, such as fasting levels of serum creatinine (SCr), albumin, plasma tHcy, folate, B(12), and pyridoxal-5'-phosphate (PLP) in chronic Korean renal transplant recipients (RTR). DESIGN: Cross-sectional study. SETTING: Nephrology & Transplant Service in Catholic University Kangnam St. Mary's Hospital, Seoul, Korea. PARTICIPANTS: Ninety-one chronic Korean RTR with stable renal function who were > or =6 months post-transplant. MEASURES: Used medical record review and anthropometric measurements, and overnight (10 to 14 hours) fasting blood samples were measured for plasma tHcy, PLP, folate, B(12), SCr, and albumin. RESULTS: The prevalence of hyperhomocysteinemia (tHcy > 12 micromol/L) was 56%, and 47% had low plasma folate levels (<3 ng/mL). Linear modeling with analysis of covariance adjusted for age, sex, albumin, SCr, and plasma B-vitamin status revealed that only SCr (standard regression coefficient R = +0.663, P<.001), plasma folate (R = -0.276, P =.001), and B(12) (R = -0.149, marginal, P =.08) were independent determinants of fasting tHcy levels in this patient population. CONCLUSION: Renal function is the major independent determinant of the fasting tHcy levels among chronic, stable Korean RTR, and that B-vitamin status plays a secondary role among such patients.

Adult↗

PubMed2000

Distribution of HLA-A, -B and -DRB1 alleles in patients with sudden sensorineural hearing loss.

This study was performed to investigate the association between human leukocyte antigen (HLA) and susceptibility to sudden sensorineural hearing loss in the Korean population. HLA-A and HLA-B typing using a standard microlymphocytotoxicity technique and HLA-DRB1 genotyping were performed in 35 patients with sudden sensorineural hearing loss and in 206 healthy controls. Prednisone (usual dose 60 mg/day) was administered for 6 days and tapered for an additional 4-6 days. Both initial hearing levels at the onset of deafness and final hearing levels after treatment were examined and evaluated for association with HLA alleles. The frequency of HLA-DRB1*14 was increased in patients with sudden sensorineural hearing loss compared with controls (relative risk [RR] = 2.7, p = 0.016). The frequencies of HLA-A2, -A31, -B52, -B61, -DRB1*04, -DRB1*11 and -DRB1*12 were slightly higher than in the controls, but did not reach statistical significance. When an association between the treatment results and HLA alleles was also evaluated, the frequency of HLA-DRB1*04 was found to be increased in the patients who did not respond to steroid treatment compared with both patients who responded well to steroid (50%, vs 16%, p = 0.034) and controls (RR = 3.0, p = 0.046). These results suggest that there is an association between HLA-DRB1*14 and disease susceptibility and that the presence of HLA-DRB1*04 may be an useful marker for predicting a poor prognosis in Korean patients with sudden sensorineural hearing loss.

Adult↗