Biomedical subjects

Lyoung Hyo Kim

Publications and source records attributed to Lyoung Hyo Kim.

31 records · Page 2Linked to original sources

PubMed2004

Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs, PPAR-alpha, -gamma, and -delta, have been characterized, and they are distinguished from each other by tissue distribution and cell activation. All PPARs are, to different extents, activated by fatty acids and derivatives. Recently, it has been shown that PPAR-delta serves as a widespread regulator of fat burning, suggesting that it might be a potential target in the treatment of obesity and type 2 diabetes. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced PPAR-delta, including -1,500 bp of the 5' flanking region. Nine polymorphisms were identified in PPAR-delta: four in the intron, one in the 5' untranslated region (UTR), and four in the 3' UTR. Among identified polymorphisms, five common sites, including c.-13454G>T, c.-87T>C, c.2022+12G>A, c.2629T>C, and c.2806C>G, were genotyped in subjects with type 2 diabetes and normal control subjects (n = 702). The genetic associations with the risk of type 2 diabetes and metabolic phenotype were analyzed. No significant associations with the risk of type 2 diabetes were detected. However, several positive associations of PPAR-delta polymorphisms with fasting plasma glucose and BMI were detected in nondiabetic control subjects. The genetic information about PPAR-delta from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases.

Aged↗

PubMed2003

Association of tumor necrosis factor polymorphisms with asthma and serum total IgE.

Tumor necrosis factors (TNF; TNFA and TNFB) are major pro-inflammatory cytokines that are thought to be important in the pathogenesis of asthma. However, the functions of genetic polymorphisms in these cytokines have not been thoroughly examined in the context of asthma pathology. In an effort to discover polymorphism(s) in genes whose variant(s) have been implicated in asthma phenotypes, we examined the genetic effects of TNF (TNFA and TNFB) polymorphisms on asthma and total serum IgE level. Seven common single-nucleotide polymorphisms (SNP) in TNF genes were genotyped in a Korean asthma cohort (asthmatics n=550, normal controls n=171). Six common haplotypes could be constructed in the TNF gene cluster due to very strong LD between TNFA and TNFB, located 13 kb apart on chromosome 6p21. One SNP (TNFA-308G>A) showed a significant association with the risk of asthma (P=0.0004). The frequency of TNFA-308A allele-containing genotype in asthmatics (9.8%) was much lower than that in normal controls (22.9%). The protective effects of this polymorphism on asthma were also evident in separated subgroups by atopic status (P=0.05 in non-atopic subjects and P=0.003 in atopic subjects). The most common haplotype of the TNF gene (TNF-ht1[GGTCCGG]) was associated with total serum IgE (immunoglobulin E) levels in asthma patients, especially in non-atopic patients (P=0.004). Genetic variants of TNF might be involved in development of asthma and total serum IgE level in bronchial asthma patients. The results of this study could be helpful to understand the function of important TNF genes in asthma and IgE production.

Adolescent↗

PubMed2003

Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection.

The mechanisms underlying the resolution of hepatitis B virus (HBV) infection remain undetermined. Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in host immune response to HBV, and the capacity for cytokine production in individuals has a major genetic component. The aim of this study was to examine whether TNF-alpha promotor polymorphisms are associated with the clearance of HBV infection. A total of 1400 Korean subjects were enrolled in two different groups: 'chronic carrier group' (CC; n=1109), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and 'subjects who spontaneously recovered' (SR; n=291), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. TNF-alpha promoter polymorphisms at positions -1031T>C, -863C>A, -857C>T, -376G>A, -308G>A, -238G>A and -163G>A were determined and the genotype distributions of the CC and SR groups were compared. The TNF-alpha promoter alleles that were previously reported to be associated with higher plasma levels, i.e. the presence of the -308A allele (TNF-alpha-308A/G or A/A) or the absence of the -863A (TNF-alpha-863C/C) variant, were strongly associated with the resolution of HBV infection in three alternative analyzing models, i.e. TNF-alpha-308G>A (P=0.01) and TNF-alpha-863C>A (P=0.003-0.14), respectively. Haplotype analysis also revealed that TNF-alpha haplotype 1 [-1031T; -863C; -857C; -308G; -238G; -163G] and haplotype 2 [-1031C; -863A; -857C; -308G; -238G; -163G] were significantly associated with HBV clearance, showing protective antibody production and persistent HBV infection, respectively (P=0.003-0.02). Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-alpha might be an important factor, which might explain the variable outcome of HBV infection.

Adult↗

PubMed2003

Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.

Transforming growth factor-beta1 (TGF-beta1) can act as both a tumor suppressor and a stimulator of tumor progression. We have examined the relationship between polymorphisms of the TGF-beta1 gene and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. A total of 1,237 Korean subjects were prospectively enrolled; 1,046 patients with chronic HBV infection and 191 healthy controls with no evidence of recent or remote HBV infection. The patients were divided into two groups: those without (n = 809) and those with HCC (n = 237). Single nucleotide polymorphisms (SNPs) of TGF-beta1 were searched for and genotyped using the single base extension method. In Korean subjects, only two SNPs were found among the seven known polymorphisms of TGF-beta1, at position -509 and in codon 10. The risk of HCC was significantly lower in patients with the T/T or C/T genotypes than in those with the C/C genotypes at position -509 (P < 0.02), and also lower among those with the Pro/Pro or Leu/Pro genotypes than in those with the Leu/Leu genotypes in codon 10 (P < 0.007). Haplotype analysis revealed that the possession of [-509C > T; L10P] conferred a decreased likelihood of HCC (OR = 0.74; 95% CI, 0.59-0.93; P = 0.008). In conclusion, the presence of the TGF-beta1 -509C > T promoter or of the L10P polymorphism, and the combination of both [-509C > T; L10P] as a haplotype were strongly associated with a reduced risk of HCC in patients with chronic HBV infection.

Adult↗

PubMed2003

Association of Eotaxin gene family with asthma and serum total IgE.

The Eotaxin gene family (Eotaxin1, Eotaxin2 and Eotaxin3) recruits and activates CCR3-bearing cells such as eosinophils, mast cells and Th2 lymphocytes that play a major role in allergic disorders. To date, the effect of polymorphisms of Eotaxin genes on asthma phenotypes has not been thoroughly examined. In our research, we sequenced whole regions of the Eotaxin gene family to identify polymorphisms, which may be involved in the development of asthma and total serum IgE. We have identified 37 SNPs in the Exotaxin gene family (Exotaxin1, 2 and 3), and 17 common polymorphic sites were selected for genotyping in our asthma cohort (n=721). Statistical analysis revealed that the EOT2+1265A>G G* allele showed significantly lower frequency in asthmatics than in normal healthy controls (0.14 versus 0.23, P=0.002), and that distribution of the EOT2+1265A>G G* allele-containing genotypes was also much lower in asthmatics (26.3 versus 40.8%, P=0.003). In addition, a non-synonymous SNP in Eotaxin1, EOT1+123Ala>Thr showed significant association with total serum IgE levels (P=0.002-0.02). The effect of EOT1+123Ala>Thr on total serum IgE appeared in a gene-dose-dependent manner. Our findings suggest that the development of asthma may be associated with EOT2+1265A>G polymorphisms, and the susceptibility to high IgE production may be attributed to the EOT1+123Ala>Thr polymorphism. Eotaxin variation/haplotype information identified in this study might provide valuable insights into strategies for the control of asthma.

Adolescent↗

PubMed2003

Association between interleukin 6 promoter variants and chronic hepatitis B progression.

Interleukin 6 (IL6) plays an essential role in the regulation of immune response to chronic disease. In this study, the three known single nucleotide polymorphisms (SNPs) in the IL6 promoter region were genotyped in a large chronic hepatitis B cohort to evaluate the effects of IL6 promoter variants. The single base extension method was used for this genotyping. Haplotypes were constructed by the three SNPs in IL6. Allele frequencies were compared for; i) patients with chronic hepatitis (CH) and chronic carriers vs. chronic hepatis patients with clinical evidence of liver cirrhosis (LC) (i.e., portal hypertension), ii) cirrhotic patients with hepatocellular carcinoma (HCC) vs. without HCC by logistic regression, and iii) with respect to the time intervals from the onset of infection to HCC. Results were analyzed by Cox relative hazard analysis on the assumption that all the patients were infected during early infancy. The frequencies of each SNP were 0.002 (IL6-597 G>A), 0.25 (IL6-572 C>G) and 0.002 (IL6-174 G>C), respectively, in the Korean population (n = 1,046). No significant associations were detected between IL6-572 C>G and chronic hepatitis B outcome in this study; i.e., LC occurrence on CH (OR = 0.16-1.27, P = 0.13- 0.71) and HCC occurrence on LC (OR = 1.04-1.23, P = 0.89-0.60) of heterozygotes and homozygotes for G allele in referent comparison to homozygotes for common allele (C/C genotype), and time interval to HCC (RH = 0.67-1.00; P = 0.14-0.99). In conclusion, there appeared to be no significant associations between IL6 promoter variants and disease outcome in chronic hepatitis B.

Aged↗

PubMed2003

Association of interleukin-6 promoter variant with bone mineral density in pre-menopausal women.

Interleukin-6 (IL6) has many roles essential to the regulation of the immune response, hematopoiesis, and bone resorption. Three single-nucleotide polymorphisms (SNP) in the IL6 promoter region were genotyped by the single-base extension method. The frequencies of each SNP were 0.002 ( IL6-597 G--> A), 0.27 ( IL6-572 G--> C), and 0.002 ( IL6-174 G--> C) in a Korean population ( n=1,082). IL6-597 G--> A and IL6-174 G--> C were totally linked together ( d(2)=1) and showed very low allele frequencies (0.002), which are common in Caucasians. On the other hand, the frequency of the IL6-572 G--> C*C allele was much higher (0.27) than that in Caucasian populations (<0.07). One of the IL6 promoter SNPs, viz., IL6-572 G--> C, showed significant associations with bone mineral density (BMD), i.e., the C allele was associated with increased BMD ( P=0.02, co-dominant model; P=0.007, dominant model). The mean BMD was highest in homozygous C individuals (0.67+/-0.15), lowest in homozygous G individuals (0.58+/-0.19), and intermediate in heterozygotes (0.64+/-0.21). In the present study, we describe a variant in the IL6 promoter region that shows positive association with higher BMD in a gene-dose-dependent manner in pre-menopausal women.

Adult↗

PubMed2003

Interleukin 10 haplotype associated with increased risk of hepatocellular carcinoma.

Interleukin 10 (IL10) is a powerful Th-2 cell cytokine produced by lymphoid cells that exerts its functions by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL1, TNFA, TGFB, IL6, IL8 and IL12). Genetic association analysis of a well-characterized HBV cohort revealed that one of IL10 haplotypes, IL10-ht2, was strongly associated with hepatocellular carcinoma (HCC) occurrence in gene dose-dependent manner. The frequency of susceptible IL10-ht2 was much higher in HCC patients and significantly increased in order of susceptibility to HBV progression from chronic hepatitis to liver cirrhosis and HCC among hepatitis B patients. In addition, survival analysis clearly showed that the onset age of HCC was also accelerated among chronic hepatitis B patients who were carrying IL10-ht2. Increased IL10 production mediated by IL10-ht2 suggests that up-regulated IL10 accelerates progression of chronic HBV infection, especially to HCC development.

Age of Onset↗

PubMed2003

Identification of novel SNPs in the interleukin 6 receptor gene (IL6R).

The human interleukin-6 receptor (IL6R) is responsible for signal transduction of IL6 that might have associations with immune diseases and various infectious diseases. We have sequenced all 10 exons including the putative splicing site to identify single nucleotide polymorphisms in IL6R. Seven novel single nucleotide polymorphisms (SNPs) were identified; one SNP in the promoter region (-183G>A), one synonymous SNP in exon 2 (24013G>A: Ala31Ala), one non-synonymous SNP in exon 9 (48892A>C: Asp358Ala) and four in introns (29753A>C, 42700T>C, 48869T>A and 59818C>T). The frequencies of each SNP in the Korean population (n=300) were 0.48 (-183 G>A), 0.13 (24013 G>A), 0.41 (29753A>C), 0.41 (42700T>C), 0.1 (48869T>A), 0.42 (48892A>C), and 0.07 (59818C>T), respectively. Haplotypes and their frequencies were estimated by the EM algorithm. Linkage disequilibrium coefficients (/D'/) between each SNP pair were also calculated. The information on SNPs and haplotypes in IL6R would be useful for genetic studies of this gene.

Chromosome Mapping↗

PubMed2003

Identification of variants in NFKBIA and association analysis with hepatocellular carcinoma risk among chronic HBV patients.

Human nuclear factor of kappa light chain gene enhancer in B cells inhibitor, alpha (NFKBIA) inhibits the action of NF-kappaB by forming a heterodimer with NF-kappaB, and preventing its translocation to the nucleus. We have sequenced a human NFKBIA full gene including -1000bp promoter region to identify its gene polymorphisms as a potential candidate gene for host genetic study of Hepatocellular Carcinoma (HCC). Nine novel single nucleotide polymorphisms (SNPs) and one GAA deletion were identified; two in promoter region (c.-673A>T, c.-642C>T), two in exon 1 (c.78G>A (Leu26Leu), c.81C>T (Asp27Asp)), three in introns (c.284T>A, c.1952A>G and c.2444C>T) and three in 3'UTR (c.2710-2712delGAA, c.2758G>A and c.3053G>A). Among ten identified variants, six were selected for larger scale genotyping (n=1,750) for association study based on frequencies and location. Haplotypes, their frequencies and linkage disequilibrium coefficients (/D'/) between SNP pairs were estimated. Allele frequencies of each SNPs and haplotypes were compared between patients with HCC and patients without HCC among HbsAg positives by logistic regression. As a conclusion, we could not find any significant association of NFKBIA variants with development of HCC among chronic hepatitis B patients.

Carcinoma, Hepatocellular↗

PubMed2003

Polymorphisms in fatty acid-binding protein-3 (FABP3) - putative association with type 2 diabetes mellitus.

Fatty acid-binding proteins (FABPs) play key roles as transport vehicles of fatty compounds throughout the cytoplasm. Human FABP3, one of the FABPs, is present in a wide variety of tissues with highest concentration in cardiac and skeletal muscle. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced the full gene of FABP3, including the -1,500bp promoter region. Fourteen polymorphisms were identified in FABP3: two ins/dels, two STRs, and ten SNPs (two in promoter, nine in intron, two in 3'UTR, and one in the 3' end). Among identified polymorphisms, five common sites including c.-530_-532delCTC, c.-345T>C, c.348+429(CA)9-18, c.246+1806G>C, and c.634+483delT were genotyped in subjects with type 2 diabetes mellitus and normal control (n=669). By logistic and multiple regression analysis, one insertion/deletion polymorphism in the 3' end (c.634+483delT) of FABP3 appeared to be weakly associated with increased risk of type 2 diabetes (OR=1.78-1.94, P=0.03-0.04) and waist/hip ratio (WHR) (P=0.03).

Carrier Proteins↗

PubMed2003

Association analysis of novel TBX21 variants with asthma phenotypes.

Human TBX21 expressed in T Cells (T-BOX21) is a Th1-specific T-box transcription factor that controls the expression of the hallmark Th1 cytokine, IFNG. As a potent candidate gene for asthma genetic study, we have sequenced the full gene of human TBX21, including the -1,500bp promoter region to identify its gene polymorphisms. Twenty-three single nucleotide polymorphisms (SNPs) were identified; one in promoter region (c.-1514T>C), one in 5'UTR (c.-138C>A), two in exon 1 (c.99C>G (p.His33Gln), c.390A>G), sixteen in introns (c.492+806T>C, c.492+1170C>A, c.492+1514G>A, c.492+1907A>C, c.492+2116G>A, c.492+2516A>G, c.492+2953C>T, c.492+4207A>T, c.492+4211A>T, c.492+4985T>A, c.492+4207G>A, c.492+5533C>T, c.492+7889T>A, c.492+8270G>C, c.768+417T>C and c.989+183C>T), one in exon 4 (c.831C>T), one in exon 6 (c.1455G>A), and one in 3'UTR (c.2103A>C). Among twenty-three identified variants, seven were selected for larger scale genotyping (n=721) for asthma association study based on frequencies and location. Haplotypes, their frequencies and linkage disequilibrium coefficients (mid R:D'mid R:) between SNP pairs were estimated. The associations with risk of asthma, skin-test reactivity and total serum IgE levels were analyzed. Using statistical analyses for association of TBX21 polymorphisms with these three asthma phenotypes, no significant signals were detected. In conclusion, we identified twenty-three genetic polymorphisms in the important TBX21 gene, but no significant associations of TBX21 variants with asthma phenotypes were detected. TBX21 variation/haplotype information identified in this study will provide valuable information for future association studies of other immunological diseases.

Adolescent↗

PubMed2003

Identification of novel variants in transforming growth factor-beta 1 (TGFB1) gene and association analysis with bone mineral density.

Human transforming growth factor-beta1 (TGFB1) is a family of polypeptides that regulate cell growth, cell differentiation, and cell function as a multifunctional regulator of cellular activity. TGFB1 is produced by osteoblasts and stored in substantial amounts in the bone matrix, which is an important regulator of both skeletal development and homeostasis of bone metabolism. In the present study, we identified four new polymorphisms in TGFB1 and examined whether these polymorphisms are risk factors for osteoporosis. We have sequenced all exons including in the promoter region up to -1,800bp to identify additional genetic polymorphisms in TGFB1. Four novel polymorphisms were newly identified: one in 5' region (g.14129555_14129557dupAGG), one in promoter region (g.14128838C>T), and two in intron (g.14106505G>A and g.14106215G>A). Two known SNPs (g.14128554C>T and g.14127139T>C) were also confirmed. The frequencies of each SNP were 0.479 (g.14129555_14129557dupAGG), 0.007 (g.14128838C>T), 0.478 (g.14128554C>T), 0.476 (g.14127139T>C), 0.016 (g.14106505G>A), and 0.004 (g.14106215G>A) in the Korean population (n=1,885), respectively. Haplotypes and their frequencies were estimated by EM algorithm, and linkage disequilibrium coefficients (mid R:/D'/: and r2) between polymorphism pairs were calculated. We analyzed genetic associations of TGFB1 polymorphisms and haplotypes with spinal bone mineral density (BMD) value of 433 postmenopausal Korean women. By statistical analysis, we could not find any associations with spinal BMD. The information from this study of the critical TGFB1 would be useful for genetic studies of other diseases.

Asian People↗