[Show abstract][Hide abstract] ABSTRACT: The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 × 10(-4)) to type 2 diabetes in overweight or obese individuals (body mass index, BMI23 kg m(-2)). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.
[Show abstract][Hide abstract] ABSTRACT: To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study.
[Show abstract][Hide abstract] ABSTRACT: To determine the spectrum and frequency of rhodopsin gene (RHO) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype-phenotype correlations in patients with mutations.
The RHO mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing.
Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (c.893C>A, p.A298D) and four known mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T, p.P347L). The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M.
The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype-phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.
[Show abstract][Hide abstract] ABSTRACT: Asthma manifests as TH2-dominant airway inflammation regulated by inducible T-cell kinase (ITK). To investigate associations between genetic variants of the ITK gene and asthma, 31 single-nucleotide polymorphisms (SNPs) were genotyped in 303 normal controls and 498 asthmatics and the two groups were compared using logistic regression models. The functional effects of the ITK promoter SNP were assessed using pGL3 luciferase reporter systems and gel-shift assays. The minor allele-196C>T in the promoter region of the ITK gene was significantly more frequent in asthmatics than in controls. The luciferase activity of the PGL3-ITK-196T allele construct was higher than that of the -196C allele. In the gel-shift assay, -196T double-stranded oligonucleotides bound more strongly to Jurkat cell nuclear protein compared to the -196C double-stranded oligonucleotides. People with the -rare allele 196C>T may be more susceptible to asthma via transcriptional regulation of the ITK gene.
Annals of Human Genetics 02/2011; 75(3):359-69. DOI:10.1111/j.1469-1809.2010.00637.x · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population.
We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.
No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).
Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.
Korean Diabetes Journal 08/2010; 34(4):229-36. DOI:10.4093/kdj.2010.34.4.229
[Show abstract][Hide abstract] ABSTRACT: The outcome of hepatitisB virus (HBV) infection can be affected by host immune factors. Interleukin-18 (IL-18) was originally
discovered as an interferon-γ-inducing factor and plays a critical role in immune response. We assessed the association between
the clearance of HBV infection and single-nucleotide polymorphisms (SNPs) in the IL-18 gene. Between March 2002 and December 2004, a total of 1,050 Korean subjects were enrolled in the study and divided into
two groups: (1) the HBV spontaneous recovery group (n=320) and (2) the chronic HBV carrier group (n=730). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions −667G>T, −148G>C, +8925C>G, and +13925A>C. We observed that the subjects bearing the IL-18 −148C allele [odds ratio (OR), 0.25; confidence interval (CI), 0.09–0.68; P=0.01], the +8925G allele (OR, 0.36; CI, 0.15–0.88; P=0.02), and the +13925C allele (OR, 0.25; CI, 0.13–0.82; P=0.01) were significantly associated with HBV clearance in a recessive model. This study indicates that the −148C, +8925G, and +13925C alleles of the IL-18 gene are likely associated with HBV clearance in a Korean population.
KeywordsHepatitisB-Single-nucleotide polymorphism (SNP)-Interleukin-18 (IL-18)
[Show abstract][Hide abstract] ABSTRACT: Background/AimThe natural course of hepatitisB virus (HBV) infection is likely related to host immune factors. Interleukin-18 (IL-18) plays
a significant role in immune defense. This study was undertaken to determine the association between the presence of hepatocellular
carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in the IL-18 gene in HBV-infected patients.
MethodsBetween March 2002 and December 2004, 730 Korean subjects were enrolled in two different groups: (1) chronic carrier without
HCC (n=637) and (2) HCC (n=93). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions −667G>T, −148G>C, +8925C>G, and +13925A>C in the study subjects. To evaluate the functional significance of SNPs in the IL-18 gene promoter region, we performed a reporter gene assay in HepG2 and Hep3B cells transfected with different alleles.
−148C allele, +8925G allele, +13925C allele, and haplotype3 (TCGC) were associated with the presence of HCC in codominant and dominant models. Furthermore, functional
analyses using the reporter gene assay revealed that the −148C allele conferred significantly lower promoter activity.
ConclusionsThis study indicates that the −148C, +8925G, and +13925C alleles of the IL-18 gene are associated with the presence of HCC and the 148G>C SNP is functionally important in determining disease outcome.
[Show abstract][Hide abstract] ABSTRACT: Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.
[Show abstract][Hide abstract] ABSTRACT: The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.
Experimental and Molecular Medicine 11/2008; 40(5):523-32. DOI:10.3858/emm.2008.40.5.523 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CXCR3 is a chemokine receptor that plays important roles in mediating chemotactic signals and modulating the activation of lymphocytes. We have previously conducted a case-control study by using a candidate gene approach to investigate the association of CXCR3 polymorphisms with the risk of asthma. Results from the epidemiologic study showed that a common nucleotide variant in the CXCR3 intron (rs2280964G>A) was associated with disease susceptibility (1006 cases and 384 control subjects; odds ratio, 0.81; 95% CI, 0.69-0.94; P = .007).
The aim of our study was to evaluate the epidemiologic study and provide functional evidence for the association of rs2280964G>A with asthma by investigating the effects of intronic variant on chemokine-mediated phenotypes of human-derived T cells.
We used cell line-based in vitro and human primary T cell-based ex vivo studies to examine the functional consequences of the intronic polymorphism, focusing on the regulation of gene expression, splicing, and immune responsiveness toward activating signals.
We present functional evidence indicating that the rs2280964A allele significantly correlates with decreased CXCR3 gene expression, which would lead to variation in immune cell responses to chemokine-cytokine signals in vitro and ex vivo that includes a decrease in chemotactic activity.
These findings, in conjunction with those of our previous epidemiologic studies, might implicate a functional link between a common nucleotide variant of a chemokine receptor gene, CXCR3, and a cause for a complex-trait disease, asthma.
The Journal of allergy and clinical immunology 10/2008; 122(6):1119-1126.e7. DOI:10.1016/j.jaci.2008.09.026 · 11.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) gene that have significant associations with the pathogenesis of polycystic ovary syndrome (PCOS) in a Korean population.
One hundred thirty-four patients with PCOS and 100 healthy women as controls.
Frequencies of genotypes for SNPs in VEGF gene, which were specifically expressed in a Korean population.
After genotypic analysis, we found that among 10 SNPs, one novel SNP at site +9812 and one known SNP at site +13553 have P values lower than .05 (+9812: odds ratio [95% confidence interval] 0.61 [0.39-0.95]; +13553: odds ratio [95% confidence interval] 0.59 [0.37-0.93]) and one haplotype (ht4) also has a P value in the significant range (odds ratio [95% confidence interval] 0.34 [0.16-0.74]).
We concluded that one novel SNP at +9812 site, one known SNP at +13553 site, and one selected haplotype in the VEGF gene have a high possibility of significant associations with the pathogenesis of PCOS in a Korean population.
Fertility and sterility 07/2008; 89(6):1751-9. DOI:10.1016/j.fertnstert.2007.06.049 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). We observed reproducibility of these results using the KHGS data; LEP+4950G>A and +4998A>C were significantly associated with systolic blood pressure and low-density lipoprotein cholesterol level, respectively. In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits.
[Show abstract][Hide abstract] ABSTRACT: To investigate several single nucleotide polymorphisms (SNPs) in the insulin receptor (INSR) gene that have significant associations with pathogenesis of polycystic ovary syndrome (PCOS) in a Korean population.
134 patients with PCOS and 100 healthy women as controls.
All exons of INSR in DNA samples from 100 healthy women and 134 women with PCOS were sequenced and compared.
Frequencies of genotypes for several SNPs in INSR gene that were found as specifically expressed SNPs in a Korean population.
Among nine SNPs analyzed in a large population, the genotypic frequencies of eight SNPs were similar, and they had no statistically significant association with PCOS. However, the frequency of a minor allele for one novel SNP, +176477 C>T, was higher in the control group than the patient group.
Among the analyzed SNPs, +176477 C>T, a novel SNP in the INSR gene, was associated with the pathogenesis of PCOS in a Korean population.
Fertility and sterility 05/2008; 89(5):1213-20. DOI:10.1016/j.fertnstert.2007.05.026 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease is caused by multiple genetic and environmental factors. The disease is also closely associated with cardiovascular conditions such as hypertension. In order to investigate any possible role of hypertension candidate genes in the disease development and progression, we examined the association of the polymorphisms of 31 hypertension candidate genes with coronary artery disease.
Genetic polymorphisms of 31 hypertension candidate genes were initially screened by resequencing DNA samples from 24 unrelated individuals in a Korean population. Association analysis was performed using 1284 unrelated Korean men, including 749 coronary artery disease subjects and 535 normal healthy controls.
We identified a total of 409 single nucleotide polymorphisms including 40 nonsynonymous single nucleotide polymorphisms, 32 insertions/deletions and four microsatellites. Among 40 nonsynonymous single nucleotide polymorphisms, 29 were examined for an association with coronary artery disease. A significant association with coronary artery disease was observed in a polymorphism of the ADD1 gene (Gly460Trp; +29017G/T) (odds ratio 0.71-0.81; P = 0.01-0.04). The same polymorphism was also associated with the number of arteries with significant coronary artery stenosis in the coronary artery disease patients (P = 0.01) as well as the increase in systolic blood pressure (P = 0.02).
The ADD1 Gly460Trp polymorphism is significantly associated with an increased risk of coronary artery disease as well as blood pressure, indicating that ADD1 plays a role in the pathogenesis of coronary artery disease as well as hypertension.
Journal of Hypertension 01/2008; 25(12):2413-20. DOI:10.1097/HJH.0b013e3282efedb5 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate validity and reliability of the food-frequency questionnaire (FFQ) developed for the Korean Genome Epidemiologic Study (KoGES).
FFQ was administered twice at 1-year interval (first FFQ (FFQ1) at the beginning and second FFQ (FFQ2) at the end of the study) and diet records (DRs) were collected for 3 days during each of the four seasons from December 2002 to May 2004 for those who attended the health examination center. At the end of the study period, we collected the 12-day DRs of 124 participants. The nutrient intakes from the DRs were compared with both FFQ1 and FFQ2.
The intakes of energy and some nutrients estimated from FFQ1 and FFQ2 were different from those assessed by the DRs. Especially, the consumption of carbohydrates was higher in FFQ1 and FFQ2 than in the DRs. The de-attenuated, age, sex and energy intake adjusted correlation coefficients between the FFQ2 and the 12-day DRs in Korean population ranged between 0.23 (Vitamin A) and 0.64 (carbohydrate). The median for all nutrients was 0.39. The correlations were similar when we compared nutrient densities of both methods. Joint classification of calorie-adjusted nutrient intakes assessed by FFQ2 and 12-day DRs by quartile ranged from 25.8% (vitamin A) to 39.5% (carbohydrate, iron) for exact concordance. Except vitamin A, the proportion of subjects classified into distant quartile was less than 7% in all nutrients. The median of correlations between the two FFQs 1 year apart were 0.45 for all nutrient intakes and 0.39 for nutrient densities.
We conclude that the FFQ we have developed appears to be an acceptable tool for assessing the nutrient intakes in this population. Further studies for calibration of the FFQ collected from multicenters participating in the KoGES are needed.
This study was supported by the budget of the National Genome Research Institute, Korea National Institute of Health (2002-347-6111-221).
European Journal of Clinical Nutrition 01/2008; 61(12):1435-41. DOI:10.1038/sj.ejcn.1602657 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ITGA1 is involved in the early remodeling of osteoarthritic cartilage and plays an essential role in the regulation of mesenchymal stem cell proliferation and cartilage production. We investigated the association between bone parameters and ITGA1 polymorphisms and their haplotype linkage disequilibrium (LD) blocks (BL_hts). Genetic susceptibility to osteoporosis was studied in 946 postmenopausal Korean women.
We identified 67 genetic polymorphisms in ITGA1 region by direct sequencing (n = 114). Eight SNPs were genotyped to further investigate their potential involvement in osteoporosis in postmenopausal women (n = 946). Areal BMD of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry.
The SNPs, +73187C>T (exon 3) and +76969T>G (intron 5), and their BL_hts were associated with bone mineral density (BMD) at various femur sites (p = 0.009-0.05). Moreover, +159174A>C (intron 28) and its haplotype BL3_ht1 showed a highly significant association with risk of non-vertebral fracture (p = 0.002-0.005) and the minor allele of +159174A>C showed a protective effect.
These results are suggestive of the association of ITGA1 with osteoporosis and related risk in postmenopausal women.
Bone 12/2007; 41(6):979-86. DOI:10.1016/j.bone.2007.08.034 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.
We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.
We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.
Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.
BMC Medical Genetics 11/2007; 8(1):70. DOI:10.1186/1471-2350-8-70 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The genetic effects of FLT3 polymorphisms on BMD and fracture risk in postmenopausal women were studied. We found that FLT3+13348C>T polymorphism and haplotype 2 were significantly associated with low BMD and high risk of fracture.
FMS-related tyrosine kinase 3 (FLT3) has been shown to play a critical role in the development of myelolymphoid progenitors and in the development of osteoclasts, but any possible genetic effect of FLT3 on bone metabolism has not been studied.
To study a possible genetic effect of FLT3, we directly sequenced the FLT3 gene in 24 Korean individuals and identified 23 sequence variants. Seven polymorphisms were selected and genotyped in Korean postmenopausal women (n = 946).
We found that FLT3+13348C>T was associated with low BMD at the lumbar spine (p = 0.04) and femoral neck (p = 0.04). Haplotype analysis revealed that FLT3-ht2 (TTCTT) containing the rare allele in the +13348 position also showed significant association with low BMD in the lumbar spine (p = 0.04) and femoral neck (p = 0.05). Consistent with these results, the FLT3+13348C>T polymorphism and FLT3-ht2 were also significantly associated with high risk of fracture in the vertebrae (OR = 1.44-1.58; p = 0.03-0.04 and OR = 1.45-1.59; p = 0.02-0.03, respectively) and in any sites (OR = 1.34-1.81; p = 0.02-0.03 and OR = 1.34-1.81; p = 0.02-0.03, respectively).
These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.
Journal of Bone and Mineral Research 11/2007; 22(11):1752-8. DOI:10.1359/jbmr.070705 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatic stellate cells (HSC) are a type of pericyte with varying characteristics according to their location. However, the electrophysiological properties of HSC are not completely understood. Therefore, this study investigated the difference in the voltage-dependent K(+) currents in HSC.
The voltage-dependent K(+) currents in rat HSC were evaluated using the whole cell configuration of the patch-clamp technique.
Four different types of voltage-dependent K(+) currents in HSC were identified based on the outward and inward K(+) currents. Type D had the dominant delayed rectifier K(+) current, and type A had the dominant transient outward K(+) current. Type I had an inwardly rectifying K(+) current, whereas the non-type I did not. TEA (5 mM) and 4-AP (2 mM) suppressed the outward K(+) currents differentially in type D and A. Changing the holding potential from -80 to -40 mV reduced the amplitude of the transient outward K(+) currents in type A. The inwardly rectifying K(+) currents either declined markedly or were sustained in type I during the hyperpolarizing step pulses from -120 to -150 mV.
There are four different configurations of voltage-dependent K(+) currents expressed in cultured HSC. These results are expected to provide information that will help determine the properties of the K(+) currents in HSC as well as the different type HSC populations.
Yonsei Medical Journal 09/2007; 48(4):684-93. DOI:10.3349/ymj.2007.48.4.684 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease (CAD) is one of the most common forms of heart disease. It has been demonstrated that chemokine-mediated inflammation is associated with the development of CAD. In this study, in order to determine the role of CCR2, a receptor for MCP-1, in the development of CAD, we initially sequenced and identified the genetic variants of CCR2 using 24 unrelated Korean individuals' DNA samples. A total of 13 genetic variants, including 1 deletion and 12 SNPs, were identified in the Korean population. Although we could not detect any association of CCR2 polymorphic markers with CAD, several SNP markers of CCR2 gene showed highly significant signals with the number of arteries with significant coronary artery stenosis in the CAD male patients. The most significant signal was detected at the SNP located at exon 2 (+780T>C, Asn260Asn) CI: 1.19-1.87, P=0.0005 (odds ratio: 1.49, 95% CI: 1.19-1.87, p=0.0005) (Table 3). This result indicates that CCR2 can play a role in the pathogenesis of CAD, especially to the number of vessels in CAD.