Association analysis of sphingomyelinase 2 polymorphisms for the extrinsic type of atopic dermatitis in Koreans.
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Asian People↗
Biomedical subjects
Hyoung Doo Shin
Publications and source records attributed to Hyoung Doo Shin.
Associations of catalase gene polymorphisms with bone mineral density and bone turnover markers in postmenopausal women.
BACKGROUND: Oxidative stress has been recently suggested to play a part in the development of osteoporosis. Catalase is a major antioxidant enzyme that detoxifies hydrogen peroxide by converting it into water and oxygen, thereby preventing cellular injury by oxidative stress. AIMS: To examine the associations between the catalase gene (CAT) polymorphisms and bone mineral density (BMD) and bone turnover markers in postmenopausal Korean women. METHODS: All exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Among 18 variants identified by a direct sequence method, four polymorphisms were selected and genotyped in all study participants (n = 560). BMD at the lumbar spine and proximal femur was measured using dual-energy x ray absorptiometry. Serum osteocalcin concentrations and bone-specific alkaline phosphatase activity were determined by an immunoradiometric assay and an immunoassay, respectively. RESULTS: The mean (standard deviation) age of the participants was 59.4 (7.2) years. Multivariate analysis showed an association of the +22348C-->T polymorphism with BMD at the lumbar spine (p = 0.01 in the dominant model) and at femur neck (p = 0.05 in the dominant model), and with serum osteocalcin level (p = 0.008 in the dominant model). Haplotype analyses showed that HT4 (-20T, +144C, +22348T, +33078A) was significantly associated with higher BMD at various sites (p<0.001-0.03) and with lower serum osteocalcin levels (p = 0.01 in the codominant model). CONCLUSIONS: These findings indicate that the +22348C-->T polymorphism and HT4 of CAT may be useful genetic markers for bone metabolism.
Aged↗
Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance.
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.
Adult↗
Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women.
Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P = 0.002). That is, the highest osteocalcin levels (34.5 +/- 16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6 +/- 14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8 +/- 10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.
Aged↗
Putative association of RUNX1 polymorphisms with IgE levels in a Korean population.
RUNX1, a member of the runt domain gene family of transcription factors, encodes a heterodimeric transcription factor and regulates the expression of various genes related to hematopoiesis and myeloid differentiation. RUNX1 has been one of the target genes for research into various autoimmune diseases due to its properties as a transcription factor and functional distribution for chromosomal translocation. In an effort to identify additional gene polymorphisms in which variants have been implicated in asthma, we investigated the genetic polymorphisms in RUNX1 to evaluate it as a potential candidate gene for a host genetic study of asthma and IgE production. We identified 19 sequence variants by direct DNA sequencing in 24 individuals of which four common variants were selected for genotyping in our asthma cohort (1,055 asthmatic patients, 384 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, two polymorphisms in the promoter region (-2084G>C and -1282G>A) showed a marginal association with total IgE levels (0.03 and 0.03 in recessive models, respectively). Our findings suggest that polymorphisms in RUNX1 might be one of the genetic factors for the regulation of IgE production.
Adolescent↗
Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.
CONTEXT: Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. OBJECTIVE: The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. DESIGN AND PATIENTS: The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed. RESULTS: Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). CONCLUSION: The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.
Aged↗
Polymorphisms in interleukin 8 and its receptors (IL8, IL8RA and IL8RB) and association of common IL8 receptor variants with peripheral blood eosinophil counts.
Airway inflammation is a major factor in the pathogenesis of asthma. Interleukin 8 (IL8) is a potent proinflammatory cytokine that interacts with its receptors, IL8RA and IL8RB. We investigated the genetic polymorphisms in IL8, IL8RA, and IL8RB for any association with risk of asthma and peripheral blood eosinophil counts in a Korean population. By carrying out direct sequencing in 24 individuals, we identified 20 sequence variants within exons and their flanking regions, including the 1.5 kb promoter regions of IL8, IL8RA, and IL8RB. Among them, seven common single-nucleotide polymorphisms (SNPs) were selected for genotyping in our asthma cohort (n = 1,439). Two common haplotypes in IL8 and three in IL8RA and IL8RB (defined as one block) were identified. Although none of the polymorphisms showed a significant association with risk of asthma, IL8RA-B ht2 showed a significant association with the peripheral blood eosinophil counts (%) among asthma patients, e.g., lower eosinophil levels among individuals with the homozygous IL8RA-B ht2 (3.55 +/- 3.39%) than among other asthmatic patients (5.52 +/- 5.55%; P (corr) = 0.018). Our findings suggest that polymorphisms and haplotypes in IL8RA and IL8RB might be among the genetic factors underlying production of peripheral blood eosinophil.
Adolescent↗
Growth hormone-releasing hormone (GHRH) polymorphisms associated with carcass traits of meat in Korean cattle.
BACKGROUND: Cold carcass weight (CW) and longissimus muscle area (EMA) are the major quantitative traits in beef cattle. In this study, we found several polymorphisms of growth hormone-releasing hormone (GHRH) gene and examined the association of polymorphisms with carcass traits (CW and EMA) in Korean native cattle (Hanwoo). RESULTS: By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428) and five marker haplotypes (frequency > 0.1) were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA. CONCLUSION: Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle.
Animals↗
IGF2 polymorphisms are associated with hepatitis B virus clearance and hepatocellular carcinoma.
The aim of this study was to determine whether IGF2 polymorphisms are associated with the clearance of hepatitis B virus (HBV) infection and the risk of hepatocellular carcinoma (HCC). A total of 1095 Korean subjects were prospectively enrolled in this case-control study. The rates of IGF2 polymorphisms were determined in each group. The IGF2+820G allele (IGF2+820G/G) and the IGF2+6815A/A genotype were strongly associated with the resolution of HBV infection (OR=0.62-0.73; P=0.001-0.03 and OR=0.71; P=0.03, respectively). Haplotype analysis showed that IGF2-haplotype5 (A-C-C-T-A-T-G) and IGF2-haplotype1 (T-C-T-T-A-C-A) were significantly associated with the clearance and persistence of HBV infection (OR=0.55-0.58, P=0.009-0.01 and OR=1.31-1.65, P=0.001-0.007, respectively). On the other hand, the IGF2+2482C/C or +820G/G genotypes were significantly associated with a higher risk of HCC (OR=1.88, 1.68; P=0.04). IGF2 polymorphisms were found to be strongly associated with the clearance of HBV or the occurrence of HCC in patients with chronic HBV infection.
Adult↗
The effects of uncoupling protein 3 haplotypes on obesity phenotypes and very low-energy diet-induced changes among overweight Korean female subjects.
Responses to energy restriction tend to vary within the population because of genetic differences. In this study, we have genotyped 6 uncoupling protein 3 (UCP-3) polymorphisms (-55C/T, Int2-143G/C, Tyr99Tyr, Int3-47G/A, Int4-498C/T, and Tyr210Tyr) among 214 overweight Korean female subjects recruited from an obesity clinic. Three major haplotypes, identified with frequencies in excess of 0.04, were constructed from 6 single nucleotide polymorphisms. Association studies were then undertaken, involving the measurement of anthropometric characteristics and body composition both before and after 1 month of a energy-restriction regimen. At baseline, haplotype 1 (ht1) [CGTACC] was associated with elevated anthropometric characteristics, including body weight, waist-hip ratio, and body mass index, as well as body components, including body fat mass and body fat-free mass. After the completion of the 1-month weight control program, which involved a very low-energy (2900 kJ/d) diet, we analyzed the outcomes according to the UCP-3 genetic polymorphisms. Among the 3 principal haplotypes, ht1 [CGTACC] was significantly associated with an increased reduction in body weight, in the codominant (P=.022), dominant (P=.016), and recessive (P=.041) models. Body mass index reduction was associated with the ht1 haplotype in a similar fashion. Among the body components, changes in body fat mass were significantly associated with ht1 [CGTACC] (P=.028), but changes in body fat-free mass were not significantly associated with the UCP-3 polymorphism.
Adult↗
Polymorphisms in FOXO gene family and association analysis with BMI.
Forkhead transcription factors of the FOXO subfamily are emerging as shared components of pathways that regulate a variety of cellular functions. In an effort to identify genetic polymorphisms in candidate genes to determine associations with BMI, we sequenced all exons of the FOXO genes (FOXO1a, FOXO3a, and FOXO4) and examined their associations with BMI in a Korean population (n = 734). Sixteen polymorphisms were identified in FOXO genes: three in FOXO1a, seven in FOXO3a, and six in FOXO4. Associations of FOXO polymorphisms with BMI were analyzed using multiple regression, adjusting for age and sex as covariates. One promoter single nucleotide polymorphism in the 5' flanking region of FOXO3a showed significant association with BMI, e.g., the lowest BMI (23.3 +/- 2.69 kg/m2) was discovered in individuals who were carrying T/T, intermediate BMI (26.6 +/- 3.14 kg/m2) was found in heterozygous individuals (C/T), and the highest BMI (27.2 +/- 3.47 kg/m2) occurred in individuals who were homozygous for the major allele (C/C; p = 0.01).
5' Flanking Region↗
SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) polymorphisms are associated with end-stage renal disease in diabetic nephropathy.
Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD). Genetic susceptibility plays an important role in the development and progression of diabetic nephropathy. Previous studies have revealed that polymorphisms in the SLC12A3 (solute carrier family 12 member [sodium/chloride] 3) gene, which encodes solute carrier family 12 member 3, might contribute to genetic susceptibility to diabetic nephropathy and essential hypertension. In this study, we examined whether the SLC12A3 gene locus is associated with ESRD resulting from diabetic nephropathy. We genotyped 11 common single nucleotide polymorphisms (SNPs) in the SLC12A3 gene in 177 patients with ESRD due to type 2 diabetes and 184 patients with diabetic retinopathy but with no signs of renal involvement. Three SNPs (g.34372G>A [Arg913Gln], g.39143G>A, and g.41727C>T) were found to be associated with ESRD due to diabetic nephropathy. These three SNPs were in complete linkage disequilibrium. Haplotype 4 in block 2 (18806C, 21822C, 34372A, 39143A, 39240T, 39375C, and 41727T) showed a significant association with ESRD due to type 2 diabetes (P = 0.0028). These results suggest that the SLC12A3 gene locus is associated with ESRD due to diabetic nephropathy.
Adult↗
Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women.
Bone mineral density (BMD), the major factor determining bone strength, is closely related to osteoporotic fracture risk and is determined largely by multiple genetic factors. Semaphorin 7a (SEMA7A), a recently described member of the semaphorin family, has been shown to play a critical role in the activation of monocyte/macrophages that share progenitors with bone-resorbing osteoclasts and thus might contribute to osteoclast development. In the present study, we directly sequenced the SEMA7A gene in 24 Korean individuals, and identified 15 sequence variants. Five polymorphisms (+15667G > A, +15775C > G, +16285C > T, +19317C > T, +22331A > G) were selected and genotyped in postmenopausal Korean women (n = 560) together with measurement of the areal BMD (g/cm2) of the anterior-posterior lumbar spine and the non-dominant proximal femur using dual-energy X-ray absorptiometry. We found that polymorphisms of the SEMA7A gene were associated with the BMD of the lumbar spine and femoral neck. SEMA7A + 15775C > G and SEMA7A+22331A > G were associated with low BMD of the femoral neck (P = 0.02) and lumbar spine (P = 0.04) in a recessive model. SEMA7A-ht4 also showed an association with risk of vertebral fracture (OR = 1.87-1.93, P = 0.02-0.03). Our results suggest that variations in SEMA7A may play a role in decreased BMD and risk of vertebral fracture.
Absorptiometry, Photon↗
Polymorphisms in the leptin receptor (LEPR)--putative association with obesity and T2DM.
Leptin plays an important role in regulating adipose-tissue mass. Leptin controls energy balance and food intake through the leptin receptor in the hypothalamus of the brain, which suggests that some polymorphisms of the leptin receptor gene (LEPR) might contribute to obesity or obesity-related diseases. In an effort to identify genetic polymorphisms in a potential candidate gene for obesity and type 2 diabetes mellitus (T2DM) in the Korean population, we have sequenced the LEPR gene. Thirty-five sequence variants were identified (including 9 novel polymorphisms): 1 single nucleotide polymorphism (SNP) in the promoter region, 1 SNP in the 5' UTR, 8 SNPs in exons (3 non-synonymous SNPs), 23 SNPs in introns, 1 ins/del in the 3' UTR, and 1 SNP in the 3' downstream region. To investigate possible association of LEPR polymorphisms with body mass index (BMI) and the risk of T2DM, we genotyped for 11 polymorphisms in the Korean population (n = 1,463). Using statistical analyses, no significant associations between the genetic polymorphisms in the LEPR gene and the risk of T2DM were detected. However, one non-synonymous SNP in exon 3, +5193G > A (Arg109Lys), showed marginal association with BMI (P = 0.02) and gene dose-dependent genetic effects were observed. The present study provides information about additional genetic polymorphisms in LEPR and positive associations of those polymorphisms with BMI in the Korean population.
Aged↗
Association analysis of interleukin 5 receptor alpha subunit (IL5RA) polymorphisms and asthma.
The alpha subunit of interleukin 5 receptor (IL5RA) on chromosome 3p26-p24 is known to regulate the development and function of eosinophils. In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in asthma, we investigated the genetic polymorphisms in IL5RA to evaluate the gene as a potential candidate for a host genetic study of asthma. By direct DNA sequencing in 24 individuals, we identified 22 sequence variants within exons and flanking regions including a 1.5-kb promoter region of IL5RA; 10 common polymorphic sites were selected for genotyping in our asthma cohort (n = 587). Two haplotype blocks were identified in a Korean population. Statistical analysis revealed that one promoter SNP, c.-5993A > G, and one ins/del polymorphism in intron 3, c.-480_482insdelGTT, showed significant association with the risk of asthma development. The genetic effects of c.-5993A>G and c.-480_482insdelGTT on asthma were more apparent among atopic subjects. Our findings suggest that polymorphisms in IL5RA might be among the genetic risk factors for asthma development, especially in atopic populations. IL5RA variant/haplotype information identified in this study will provide valuable information for strategies for the control of asthma.
Adolescent↗
The effects of UCP-1 polymorphisms on obesity phenotypes among Korean female subjects.
Three SNPs of UCP-1 including A-3826G, A-1766G, and Ala64Thr (G+1068A) were genotyped among 453 overweight Korean female subjects recruited from an obesity clinic. Four common haplotypes with frequency greater than 0.04 were constructed with three SNPs. For an accurate evaluation of the effects of UCP-1 polymorphism on body fat accumulation, all subjects were tested using computerized tomography to measure the cross-sectional fat tissue areas at abdominal and distal part of the body. By statistical analyses, ht4[GAA] showed a significant association with decreased abdominal fat tissue area (P=0.02, dominant model), fat tissue area at thigh (P=0.008, dominant model), body fat mass (P=0.002, dominant model), and waist-to-hip ratio (P=0.01, dominant model). In addition, ht3[GAG] was associated with the accelerated reduction of waist-to-hip ratio and body fat mass by very low calorie diet among subjects who finished one-month-weight control program (P=0.05-0.006).
Adipose Tissue↗
CXCR3 polymorphisms associated with risk of asthma.
The chemokine (C-X-C motif) receptor 3 (CXCR3) gene, on chromosome Xq13, is known to have critical roles in inflammatory and immune responses. In an effort to discover polymorphisms have been implicated in asthma, we investigated the genetic polymorphisms in CXCR3 to evaluate it as a potential candidate gene for a host genetic study of asthma. Statistical analysis revealed that one SNP in intron 1, c.12+234G > A, showed significant association with the risk of asthma development (P = 0.007, OR = 0.81). By subgroup analyses stratified by gender and atopic status, the genetic effect of c.12+234G > A on asthma was more apparent among male atopic subjects (P = 0.0009, OR = 0.61). Our findings suggest that polymorphisms in CXCR3 might be one of the genetic factors for the risk of asthma development, especially in male atopic subjects. CXCR3 variation/haplotype information identified in this study will provide valuable information and insight into strategies for the control of asthma and its subgroup, atopy.
Adult↗
Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism.
One hundred and eleven male patients with alcohol dependence and 123 nonalcoholic healthy men were tested for the genetic polymorphisms of alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), serotonin transporter (5-HTT) and dopamine transporter (DAT1). There were significant differences in genotype frequencies of ADH2 C992G and A13543G SNPs between alcoholic patients with family history of alcohol dependence (familial) and alcoholic patients without family history (non-familial). Genotype and allele frequencies of ALDH2 G1951A SNP in familial or non-familial alcoholic patients differ from normal controls. Neither 5-HTTLPR L/S nor DAT1 G2319A SNP genotypes nor alleles discriminated alcoholic patients from normal controls. These findings suggest that the genetic characteristics of alcohol metabolism in non-familial alcoholics fall between non-alcoholism and familial alcoholics.
Adult↗