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Hyoung Doo Shin

Publications and source records attributed to Hyoung Doo Shin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Highly polymorphic human CYP4A11 gene.

The cytochrome P450 (CYP) is a monooxidase, which regulates metabolism of drugs and fatty acids in the liver and kidney. Among isoforms of the CYP4A subfamily, CYP4A11 is a major lauric acid (medium-length fatty acids) omega hydroxylase and is involved in the balance of lipids in the human liver. We performed direct DNA sequencing in 24 unrelated Korean individuals in the whole gene, including the 1-kb upstream region of CYP4A11. Seventy sequence variants were identified: six in exons, including two nonsynonymous SNPs; 60 in introns; and four in 3'UTR. In comparison with SNPs enrolled in the SNP database (dbSNP) of the National Center for Biotechnology Information (NCBI), 26 novel polymorphisms (24 in introns and two in 3'UTR) were identified in Korean subjects (n=24). The distributions of polymorphisms confirmed were significantly different from those in the dbSNP of the NCBI. Information clarified in this study would provide valuable for further studies, including genetic association studies for various diseases and drug responses.

3' Untranslated Regions↗
PubMed2005

Common interleukin 10 polymorphism associated with decreased risk of tuberculosis.

Interleukin 10 (IL10) is a powerful TH2-cell cytokine that inhibits lymphocyte replication and secretion of inflammatory cytokines. The genetic associations of polymorphisms in IL10 with clinical manifestations of tuberculosis (TB) were examined in a large number of patients with clinical TB infection (n = 459) and normal controls (n = 871). One common promoter SNP (IL10 -592 A>C) was found to be significantly associated with decreased risk of TB manifestation. The frequency of the "C"-bearing genotype was higher in normal controls than in patients with clinical TB infection (P = 0.005, OR = 0.69). A summary of the genetic effect of IL10 -1082 A>G, the other nearby promoter SNP, in other ethnic groups is also presented.

Adolescent↗
PubMed2005

Association of the OSCAR promoter polymorphism with BMD in postmenopausal women.

UNLABELLED: In an effort to identify genetic polymorphisms in potential candidate genes for osteoporosis, 10 variants were identified in the OSCAR gene using direct DNA sequencing, and 560 postmenopausal women were genotyped at five SNP loci, using the TaqMan method. The rare allele (G allele) of OSCAR-2322A>G (SNP in the 5' flanking region) showed significant association with lower BMD at various bone sites in postmenopausal women (n = 560). INTRODUCTION: BMD is the major factor for determining bone strength and osteoporotic fracture risk and is determined by both environmental and multiple genetic factors. The osteoclast-associated receptor (OSCAR) plays a critical role in osteoclast differentiation and thus is an important candidate gene for the modulation of BMD. MATERIALS AND METHODS: Through direct sequencing in 24 Korean individuals, 10 sequence variants were identified: 2 in the 5' flanking region, 7 in the exons (including 6 nonsynonymous single-nucleotide polymorphisms [SNPs]), and 1 in an intron. Five of these polymorphisms were selected for larger-scale genotyping in postmenopausal women (n = 560). Areal BMD (g/cm2) of the anterior-posterior lumbar spine and the nondominant proximal femur was measured using DXA (Lunar Expert XL and Hologic QDR 4500-A). Lateral thoracolumbar radiographs were obtained in all subjects. RESULTS: Using multiple regression analysis and controlling for age, years since menopause, height, weight, and evaluation machine as covariates, the rare allele (G allele) of OSCAR-2322A>G showed significant association with lower BMD at various bone sites in postmenopausal women. CONCLUSION: These findings suggest that the promoter variant in OSCAR gene (OSCAR-2322A>G) might be one of genetic determinants of BMD in postmenopausal women.

Absorptiometry, Photon↗
PubMed2005

Association analysis of signal transducer and activator of transcription 4 (STAT4) polymorphisms with asthma.

The signal transducer and activator of transcription 4 (STAT4) on chromosome 2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12 in lymphocytes and regulating the differentiation of T helper cells. In an effort to discover additional polymorphism(s) in genes in which variant(s) have been implicated in asthma, we investigated the genetic polymorphisms in STAT4 to evaluate it as a potential candidate gene for a host genetic study of asthma. By direct DNA sequencing in 24 individuals, we identified 12 sequence variants within introns and their flanking regions, including the 1.5 kb promoter region of STAT4. Among them, seven common polymorphic sites were selected for genotyping in our asthma cohort (502 asthmatic patients, 164 normal controls). Using logistic regression analysis for association with the risk of asthma, while controlling for age, gender, and smoking status as covariates, no significant associations with the risk of asthma were detected. However, one single nucleotide polymorphism (SNP) in intron 11 (+90089T--> C) and two haplotypes showed positive association (P= 0.03, 0.03 and 0.03, respectively) with production of specific IgE to Dermatophagoides farinae (D.f.) or Dermatophagoides pteronyssinus (D.p.) among asthmatic patients. The minor allele frequencies of +90089T--> C and BLOCK2-ht1 were higher (0.54 and 0.47, respectively) among individuals who produced specific IgE to D.f. or D.p. than frequencies (0.47 and 0.39, respectively) among individuals who did not produce specific IgE (OR=1.38 and 1.40, respectively). Our findings suggest that polymorphisms in STAT4 might be one of the genetic factors for the risk of production of specific IgE to mite allergens.

Age Factors↗
PubMed2005

DNase II polymorphisms associated with risk of renal disorder among systemic lupus erythematosus patients.

DNase II is an important enzyme for DNA fragmentation and degradation during programmed cell death and, consequently, a potential candidate gene for genetic study of systemic lupus erythematosus (SLE). Genetic associations of DNase II with SLE and related phenotypes were examined in Korean patients with SLE. A total of 350 Korean SLE patients and 330 healthy subjects were enrolled. Direct DNA sequencing and TaqMan were employed. Logistic regression analyses were performed to examine the genetic association with SLE and related phenotypes. Through direct sequencing in 24 Korean individuals, six sequence variants were identified: one in the 5' flanking region, four in exons (including one nonsynonymous), and one in the 3' flanking region. Four of these polymorphisms were selected for a larger-scale genotyping (350 SLE patients and 330 normal controls). No significant associations with the risk of SLE were detected. However, further analyses of association with the risk of renal disorder among SLE patients revealed several positive associations. One promoter SNP (-1066G>C), +2630T>C (Ser145Ser), +6235G>C and one haplotype showed weak associations with the risk of nephritis among SLE patients.

Endodeoxyribonucleases↗
PubMed2005

A single nucleotide polymorphism on the promoter of eotaxin1 associates with its mRNA expression and asthma phenotypes.

Eotaxin1 plays a pivotal role in eosinophil-associated inflammation. Previously, we demonstrated 14 single-nucleotide polymorphisms (SNPs) in the human eotaxin1 gene and the association between the EOT+67G>A allele and the level of IgE. In this study, we investigated the association between the SNPs and plasma eotaxin1 levels, peripheral blood eosinophil counts, and PC20 methacholine values in normal and asthmatic subjects, and the effects of SNPs on the process of eotaxin1 production. The EOT-576C>T and EOT-384A>G polymorphisms and haplotypes (ht1 and ht4) were significantly associated with plasma eotaxin1 levels in the asthmatics (p < 0.001-0.040). The log [plasma eotaxin1] values correlated with the log [serum total IgE] values in the asthmatics and the normal controls (p = 0.012 and p = 0.004, respectively), and with the log [PC20 methacholine] values in the asthmatics (p = 0.014). A DNA-protein complex was formed with EOT-384A>G, but not with the other SNPs of the promoter. The interaction was stronger with the minor allele than with the common allele, and was reduced upon TNF-alpha exposure. TNF-alpha-stimulated PBMCs from the asthmatics with the minor allele homozygote expressed significantly lower levels of eotaxin1 mRNA than those from individuals with the common allele. The EOT+67G>A polymorphism, which substitutes alanine with threonine, did not affect eotaxin1 production or activity. Our data suggest that the EOT-384A>G SNP participates in the regulation of eotaxin1 expression by providing a potential binding site for a repressor, and that the ANOVA of EOT-384A>G may predict asthma phenotypes.

Adult↗
PubMed2005

Association analysis of monocyte chemotactic protein-3 (MCP3) polymorphisms with asthmatic phenotypes.

The monocyte chemotactic protein-3 (MCP3), on chromosome 17q11.2-q12, is a secreted chemokine, which attracts macrophages during inflammation and metastasis. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in asthma, we scrutinized the genetic polymorphisms in MCP3 to evaluate it as a potential candidate gene for asthma host genetic study. By direct DNA sequencing in twenty-four individuals, we identified four sequence variants within the 3 kb full genome including 1,000bp promoter region of MCP3; one in promoter region (-420T>C), three in intron (+136C>G, +563C>T, +984G>A) respectively. The frequencies of those four SNPs were 0.020 (-420T>C), 0.038 (+136C>G), 0.080 (+563C>T), 0.035 (+984G>A), respectively, in Korean population (n = 598). Haplotypes, their frequencies and linkage disequilibrium coefficients (|D'|) between SNP pairs were estimated. The associations with the risk of asthma, skin-test reactivity and total serum IgE levels were analyzed. Using statistical analyses for association of MCP3 polymorphisms with asthma development and asthma-related phenotypes, no significant signals were detected. In conclusion, we identified four genetic polymorphisms in the important MCP3 gene, but no significant associations of MCP3 variants with asthma phenotypes were detected. MCP3 variation/haplotype information identified in this study will provide valuable information for future association studies of other allergic diseases.

Adolescent↗
PubMed2005

Scanning of genetic effects of alcohol metabolism gene (ADH1B and ADH1C) polymorphisms on the risk of alcoholism.

Alcoholism is a multifactorial and polygenic disorder involving complex gene-to-gene and gene-to-environment interactions. Alcohol metabolism is one of the biological determinants that could significantly be influenced by genetic polymorphisms in alcohol-metabolism genes. These genetic polymorphisms are believed to influence drinking behavior and development of alcoholism. Direct DNA sequencing of whole ADH1B and ADH1C genes revealed 36 sequence variants, including six nonsynonymous and 14 novel polymorphisms. Seventeen polymorphisms among them were selected for genotyping in a larger study (n = 352) based on linkage disequilibria (LDs) among SNPs, locations, and frequencies. Hardy-Weinberg equilibrium (HWE) analyses of polymorphisms revealed severe deviations only in alcoholics, which strongly suggest that a selection bias (or pressure) may be involved. The analyses of genotype distribution in alcoholics (n = 106) and normal controls (n = 246) showed dramatic associations with the risk of alcoholism. Fourteen polymorphisms in ADH1C and ADH1B showed a series of different strengths of association and magnitudes of risk. Based on referent and subgroup analysis, it was strongly suggested that the genetic effects come from the ADH1B*47Arg/*47Arg genotype, and that the positive signals from other sites are just tracking the genetic effect of ADH1B His47Arg. In this article we present summaries of previous studies and of the present study, to give an overview of the worldwide effects of ADH1B His47Arg on the risk of alcoholism. The information derived from this study could be valuable for understanding the genetic factors involved in the risk of alcoholism and facilitate further investigation in other ethnic groups.

Adult↗
PubMed2005

Genetic polymorphisms in the transforming growth factor beta-induced gene associated with BMI.

In an effort to identify genetic polymorphisms in potential candidate genes for type 2 diabetes mellitus (T2DM), we have sequenced the transforming growth factor beta-induced gene (TGFBI), and examined the association with T2DM and diabetic phenotypes in a Korean T2DM study (775 T2DM patients and 316 normal controls). Twenty-eight polymorphisms were identified in TGFBI. Although no significant associations were detected with the risk of T2DM, one SNP in intron 16 (c.2011+137C>T) and one SNP in the 3' untranslated region (UTR) (c.2589T>G), showed significant association with the levels of insulin and body mass index (BMI) among nondiabetic controls. The lower insulin and BMI were observed in individuals who carry one or two copies of minor alleles than others. For example, the highest BMI (24.21 kg/m(2)) in individuals with homozygote major alleles (T) of c.2589T>G (n=99), the intermediate BMI (23.68 kg/m(2)) in individuals with heterozygote alleles (n=156), and the lowest BMI (22.69 kg/m(2)) in individuals with homozygote minor alleles (G) (n=57, P=0.005) were observed. The present study provides, for the first time, information about genetic polymorphisms in TGFBI and positive associations of those polymorphisms with levels of insulin and BMI in the Korean population.

3' Untranslated Regions↗
PubMed2005

Association analysis of cysteinyl-leukotriene receptor 2 (CYSLTR2) polymorphisms with aspirin intolerance in asthmatics.

OBJECTIVES AND METHODS: The cysteinyl leukotriene receptor 2 (CYSLTR2) gene on chromosome 13q14.12-q21.1 encodes a receptor for CYSLTs, potent biological mediators in the pathogenesis of asthma, particularly that associated with aspirin intolerance (AIA). In an effort to discover additional polymorphism(s), the variant(s) of which have been implicated in asthma and aspirin intolerance, we scrutinized genetic polymorphisms of the CYSLTR2 gene, and evaluated this locus as a potential candidate for asthma. RESULTS: DNA sequencing in 24 Koreans of the 5-kb region of the CYSLTR2 gene, including the approximately 1500-bp promoter region, revealed four sequence variants: one in the 5'-flanking region (c.-819T>G), two in the 3'-flanking region (c.2078C>T and c.2534A>G), and one downstream of the gene (c.2545+297A>G). The SNP frequencies were 0.499 (c.-819T>G), 0.351 (c.2078C>T), 0.429 (c.2534A>G), and 0.088 (c.2545+297A>G), and five haplotypes were constructed. The SNPs and haplotypes were not associated with risk of asthma development, but were significantly associated with aspirin intolerance. The frequencies of rare alleles on c.-819T>G, c.2078C>T, and c.2534A>G were higher in subjects with AIA than in subjects with aspirin-tolerant asthma (P=0.013-0.031). Asthmatics who had rare alleles for c.-819T>G, c.2078C>T or c.2534A>G exhibited a more pronounced fall in FEV1 after aspirin provocation than did those who carried the common allele (P=0.03-0.009). Asthmatics carrying ht2 (TTGA) also showed a more pronounced decrease in FEV1% after aspirin provocation than those carrying ht1 (GCGA) (P=0.006). These associations were even stronger when combined with LTC4S polymorphisms (-444A>C [c.-444A>C]) gene. CONCLUSION: CYSLTR2 polymorphisms are associated with aspirin intolerance in asthmatics.

Adolescent↗
PubMed2004

Association of interleukin 10 haplotype with low bone mineral density in Korean postmenopausal women.

Osteoporosis is a disease characterized by exaggerated loss of bone mass, with as much as 50 to 85% of the variation in bone mineral density (BMD) commonly accepted as being genetically determined. Although intensive studies have attempted to elucidate the genetic effects of polymorphisms on BMD and/or osteoporosis in several genes, the genes involved are still largely unknown. The possible associations of genetic variants in five-candidate genes (IL10, CCR3, MCP1, MCP2 and GC) with spinal BMD were investigated in Korean postmenopausal women (n = 370). Fourteen SNPs in five candidate genes were genotyped, and the haplotypes of each gene constructed. The associations of adjusted spinal BMD by age, year since menopause (YSM) and body mass index (BMI), with genetic polymorphisms, were analyzed using multiple regression models. Genetic association analysis of Korean postmenopausal women revealed that IL10 -592A > C and/or IL10 ht2 were associated with decreased bone mass, whereas no significant associations were observed with all polymorphisms in other genes. The levels of spinal BMD in individuals bearing the IL10 -592CC genotype were lower (0.78 +/- 0.16) than those in others (0.85 +/- 0.17) (P = 0.02), and the BMD of IL10 ht2 bearing individuals were also lower (0.82 +/- 0.15) than those in others (0.85 +/- 0.17) (P = 0.04). Our results suggest that variants of IL10 might play a role in the decreased BMD, although additional study might need to be followed-up in a more powerful cohort.

Bone Density↗
PubMed2004

Association of DNA repair gene XRCC1 polymorphisms with head and neck cancer in Korean population.

Squamous cell carcinoma of the head and neck (SCCHN), which is relatively prevalent in Korea, is believed to be induced by environmental carcinogens and host genetic factors. Accumulating evidence has shown that genetic differences in DNA repair capacity resulting from genetic polymorphism influence the risk of environmental carcinogenesis. We therefore examined the associations of genetic polymorphisms in the DNA repair genes XRCC1 with the risk of SCCHN in a Korean population (hospital-based, case-control study; 147 cases and 168 controls). Three known polymorphisms in the XRCC1 gene were genotyped: R194W(C>T) in exon 6, R280H(G>A) in exon 9 and R399G(G>A) in exon 10. Although no significant associations were apparent with R280H(G>A) and R399G(G>A), a highly significant association (p = 0.0005) of R194W(C>T) with the increased risk (OR = 2.61; 95% CI 1.53-4.46) of SCCHN was detected among patients and normal controls under dominant model. The frequency of minor allele-containing genotypes (TT and CT) was much higher in SCCHN patients (51.8%) compared to that in normal controls (30.3%) (p = 0. 0005). When considering a relatively small number of cases (n = 147) and controls (n = 168) in our study, larger studies are needed to validate the genetic effects of XRCC1 polymorphisms in Asian populations. In conclusion, the result from our study provides additional evidence of an association of the XRCC1 polymorphism (Arg194Trp) with SCCHN as markers of genetic susceptibility in the Korean population.

Adult↗
PubMed2004

Association analyses of DNA methyltransferase-1 (DNMT1) polymorphisms with systemic lupus erythematosus.

The etiology of systemic lupus erythematosus (SLE) is very complex, and genetic factors appear to play a significant role in susceptibility to SLE, in determining the disease expression, and in the autoantibody profiles of individuals with SLE. DNA methyltransferase-1 (DNMT1) is a major enzyme that determines genomic methylation patterns and both maintains methyltransferase and exhibits de novo DNA methylation activity in vivo. In order to clarify the association of DNMT1 polymorphisms with SLE, we scrutinized the genetic polymorphisms in exons and their boundaries of DNMT1, including the -1,500 bp promoter region, by direct sequencing in 24 Korean individuals. Twenty-nine sequence variants were identified: two in 5'UTR, six in exons, and 21 in introns. Eight of these polymorphisms were selected for a larger-scale genotyping (n=680) by considering their allele frequencies, haplotype-tagging status, and linkage disequilibrium coefficiencies (LDs) among polymorphisms. The associations between DNMT1 polymorphisms and the clinical profiles of SLE were analyzed. No significant associations with the risk of SLE were detected. However, further analyses of association with autoantibody production among SLE patients revealed that one nonsynonymous SNP, +14463G>C (V120L) in exon 4, was weakly associated with an increased risk of anti-La antibody production (P=0.04), although the significance could not be retained after correction of multiple tests. The DNMT1 variations and haplotypes clarified in this study would provide valuable information for future genetic studies of other autoimmune diseases.

Chromosome Mapping↗
PubMed2004

Interleukin 3 (IL3) polymorphisms associated with decreased risk of asthma and atopy.

Cytokines, having central functions in immunological and inflammatory process, are always expected to play important roles in the pathogenesis of various diseases, such as asthma. Genetic polymorphisms of those cytokine and cytokine receptor genes are the focus of genetic association studies. In an effort to identify gene(s) whose variant(s) are involved in the development of asthma, we examined the genetic effects of 19 single nucleotide polymorphisms in eight cytokine and cytokine receptor genes, including IL1A, IL1B, IL2, IL3, IL4, IL8, IL10, and IL5RA, on asthma and atopy. Nineteen single nucleotide polymorphisms in eight cytokine and cytokine receptor genes were genotyped using the single-base extension method in a Korean asthma cohort (n = 723). Logistic regression and multiple regressions were used for statistical analyses controlling for smoking, age, and gender as covariables. Genetic association analysis of polymorphisms revealed that one exonic (exon 1), IL3 + 79T > C ( Ser27Pro), showed significant association with the risk of asthma and atopy. The Pro allele had shown dominant and protective effects on development of asthma in nonatopic subjects (P = 0.002) and also showed significant association with the risk of atopy in normal control subjects (P = 0.007). This information about the genetic association of important genes with asthma might provide valuable insights into strategies for the pathogenesis of asthma and atopy.

Adolescent↗
PubMed2004

Common DNase I polymorphism associated with autoantibody production among systemic lupus erythematosus patients.

DNase I could be the most important nuclease for the removal of DNA from nuclear antigens at sites of high cell turnover, and thus may also prevent systemic lupus erythematosus (SLE). Sixteen SNPs were identified by direct DNA sequencing, among which six were selected for genotyping in a larger investigation on the basis of linkage disequilibria among SNPs, their frequency, location and haplotype tagging status. Genetic associations of polymorphisms in DNase I with the risk of SLE and the production of common autoantibodies were examined in a Korean population (350 SLE patients and 330 controls). Although no significant associations with the risk of SLE were found, logistic regression analyses revealed that one non-synonymous SNPs in exon 8, +2373A>G(Gln244Arg), was significantly associated with an increased risk of the production of anti-RNP and anti-dsDNA antibodies among SLE patients. The frequency of the homozygous minor allele (Arg/Arg) was much higher in patients who had the anti-RNP antibody (31.3%) than in patients who did not have this antibody (14.4%) (P=0.0006, OR=2.86). In addition, the A/T mutation in exon 2 of DNase reported in two Japanese SLE patients was not present in SLE patients (n=350) or controls (n=330) in our Korean population, which combined with the results of previous reports strongly suggests that the mutation is not present in three major ethnic groups: Caucasian, African and Asian.

Adolescent↗
PubMed2004

Identification of variants in cyclin D1 ( CCND1) and B-Cell CLL/lymphoma 2 ( BCL2).

CCND1 is an important cell-cycle regulatory protein associated with cell proliferation, poor prognosis and recurrence in cancer, while BCL2 is an important anti-apoptotic protein that plays a vital role in the regulation of the life span by controlling the rate of apoptosis. Recent studies have shown that CCND1 and BCL2 may be responsible for the body mass and the regulation of various metabolic processes. In an effort to discover additional polymorphism(s), we scrutinized the genetic polymorphisms in the CCND1 and BCL2. By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within the 16 kb of whole CCND1 gene: one in exon 4, 17 in introns and four in the 3' UTR region. We also found eight sequence variants within 7.5 kb exon-intron boundaries of BCL2 gene: one in promoter, three in exon 1, and four in the 3' UTR region. Haplotypes, their frequencies and linkage disequilibrium coefficients (| D'| and r(2)), among polymorphisms were estimated. Among identified variants, seven and six variants of CCND1 and BCL2 were genotyped in a larger series of subjects ( n=320). Statistical analyses of CCND1 and BCL2 polymorphisms with two metabolic phenotypes revealed no significant association. The information concerning genetic polymorphisms of CCND1 and BCL2 might provide valuable information for future genetic studies of diseases.

5' Untranslated Regions↗
PubMed2004

Identification of single nucleotide polymorphisms in the tumor necrosis factor (TNF) and TNF receptor superfamily in the Korean population.

The tumor necrosis factor (TNF) and TNF receptor (TNF-TNFR) superfamily plays crucial roles in immune regulation and host immune responses. The superfamily has been also associated with many immune-mediated diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease, and diabetes. In order to investigate genetic variants of the TNF-TNFR superfamily, a total of 63 known single nucleotide polymorphisms (SNPs) in the coding region (cSNPs) of the TNF-TNFR superfamily genes were selected from the public SNP database. Among 63 cSNPs tested in this study, only 24 SNPs (38%) were validated to be polymorphic in the Korean population by primer extension-based SNP genotyping. By means of the new enhanced single strand conformational polymorphism (SSCP) method, we also identified a total of 78 SNPs, including 48 known SNPs and 30 novel SNPs, in the 44 human TNF-TNFR superfamily genes. The newly discovered SNPs in the TNF-TNFR superfamily genes revealed that the Korean population had very different patterns of allele frequency compared with African or white populations, whereas Korean allele frequencies were highly similar to those of Asian (correlation coefficient r = 0.88, p < 0.046). A higher similarity of allele frequency was observed between Korean and Japanese populations (r = 0.90, p < 0.001). The validated SNPs in the TNF-TNFR superfamily would be valuable for association studies with several immune-mediated human diseases.

Adult↗