• The Journal of Internal Korean Medicine
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• v.28 no.2
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• pp.262-274
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• 2007

Objective : It has been reported that two-repeats ($IL1RN^{\ast}2$) of interleukin-1 receptor antagonist (IL-1Ra) gene is associated with ischemic stroke, and that Ala allele of the common Pro12Ala polymorphism in $PPAR-{\gamma}2$ isoform is associated with reduced risk for type 2 DM and its complications. The aim of the present study is to assess the association of IL-1Ra and $PPAR-{\gamma}2$ Pro12Ala polymorphism with the presence of ischemic stroke in the case of diabetic and non-diabetic patients. Methods : Genomic DNA was obtained from 373 healthy subjects, 157 DM subjects without ischemic stroke (known DM duration ${\ge}10$ years) and 302 ischemic stroke patients (including with DM). IL-1Ra polymorphism was analysed by polymerase chain reaction (PCR), and $PPAR-{\gamma}2$ polymorphism by restriction fragment length polymorphism after PCR. Results : $IL1RN^{\ast}1/IL1RN^{\ast}2$ genotype was associated with significantly increased risk for DM (OR=2.86, P = 0.0008) and ischemic stroke (OR=2.74, P = 0.0016). Pro/Ala genotype was associated with the reduced risk for DM (OR=0.53, P = 0.0491) and ischemic stroke (OR=0.38, P = 0.0039). They were also associated with the reduced risk for ischemic stroke in the DM patients compared with DM without ischemic stroke (OR=0.25, P = 0.0321). Conclusions : $IL1RN^{\ast}2$ allele could be an accelerating factor, not a predictive marker for ischemic stroke in type 2 DM. The Pro/Ala genotype of $PPAR-{\gamma}2$ Pro12Ala polymorphism may be associated with reduced risk for ischemic stroke with type 2 DM. Therefore it could be a useful predictive marker for ischemic stroke in Korean type 2 DM.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.607-622
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• 2004

Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.1
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• pp.81-87
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• 2021

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is one of the most common types of diabetes and is caused by increased insulin resistance and reduced insulin secretion. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is a master modulator of mitochondrial biogenesis and of gluconeogenesis in liver. In this study, we analyzed genetic polymorphisms of PPARGC1A gene in a middle-aged Korean population with T2DM. Using the genotype data of 736 T2DM cases and 4544 healthy controls obtained from the Korean Association Resource (KARE), we analyzed genetic correlations between single nucleotide polymorphisms (SNPs) of PPARGC1A and T2DM. Fifteen SNPs of PPARGC1A demonstrated a statistically significant association with T2DM. Of these, rs10212638 exhibited the strongest correlation with T2DM (P-value=0.015, OR=1.29, CI=1.05~1.59), and the minor G allele of PPARGC1A increased the risk of T2DM. This is the first study to report a significant association between genetic polymorphisms in PPARGC1A and T2DM and suggests that SNPs of PPARGC1A display genetic correlations to the etiology of T2DM.

• Journal of Internet Computing and Services
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• v.13 no.4
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• pp.45-52
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• 2012

T cells induce immune responses and thereby eliminate infected micro-organisms when peptides from the microbial proteins are bound to HLAs in the host cell surfaces, It is known that the more stable the binding of peptide to HLA is, the stronger the T cell response gets to remove more effectively the source of infection. Accordingly, if peptides (HLA binder) which can be bound stably to a certain HLA are found, those peptieds are utilized to the development of peptide vaccine to prevent infectious diseases or even to cancer. However, HLA is highly polymorphic so that HLA has a large number of alleles with some frequencies even in one population. Therefore, it is very inefficient to find the peptides stably bound to a number of HLAs by testing random possible peptides for all the various alleles frequent in the population. In order to solve this problem, computational methods have recently been developed to predict peptides which are stably bound to a certain HLA. These methods could markedly decrease the number of candidate peptides to be examined by biological experiments. Accordingly, this paper not only introduces a method of machine learning to predict peptides binding to an HLA, but also suggests a new prediction model so called 'knowledge-based genetic algorithm' that has never been tried for HLA binding peptide prediction. Although based on genetic algorithm (GA). it showed more enhanced performance than GA by incorporating expert knowledge in the process of the algorithm. Furthermore, it could extract rules predicting the binding peptide of the HLA alleles common in Koreans.

• Clinical and Experimental Pediatrics
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• v.49 no.12
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• pp.1340-1347
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• 2006

Purpose : The aim of the present study was to investigate the role of polymorphic cytosine adenine (CA) repeat of the IGF-I gene in the age-related alterations of serum IGF-I levels in healthy children. Methods : Two hundred and forty three normal healthy children (136 boys; 107 girls) aged between 7 and 15 years were enrolled in the present study. The primers were designed to cover the promoter regions containing the polymorphic CA repeat. Data were analyzed using GeneMapper software, version 3.7. All analyses were performed using MEDCALC software packages. Results: Deletion of 2 bp (G, A) following 3' of CA repeat were observed in all Korean children. The CA repeat sequences ranged from 17 to 23, and 19 CA repeat were the most common with an alleles frequency of 39.3 percent. Considering genotypes, 63.8 percent of subjects were homozygote or heterozygote for 19 CA repeat (192 bp allele), suggesting that this is wild type allele from which all other alleles originated in Korean children. Homozygote for 19 CA repeat were 14.7 percent, heterozygote for 19 CA repeat was 49.1 percent and 19 CA noncarriers totalled 36.2 percent. In 19 CA repeat noncarriers, the mean height, weight and serum IGF-I level were lower compared with those of 19 CA homozygous carriers, but statistically not significant. Correlations between serum IGF-I level and age according to the IGF-I genotypes revealed statistically significant relationships in the all groups, in the 19 CA repeat carrier group and, even in the noncarrier group. Conclusions : There were no significant differences of the mean height, weight and serum IGF-I levels among three different genotype groups. Also, there were no significantly different correlations between 19 CA repeat polymorphisms and serum IGF-I levels, according to genotype. Our results suggest that the IGF-I 19 CA repeat gene polymorphism is not associated with circulating IGF-I levels in healthy children.

• Proceedings of the Korean Environmental Health Society Conference
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• 2003.06a
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• pp.24-25
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• 2003

Lead is ubiquitous in the human environment as a result of industrialization. China's rapid industrialization and traffic growth have increased the potential for lead emissions. Lead poisoning in children is one of the most common public health problems today, and it is entirely preventable. Children are more vulnerable to lead pollution and lead in their bodies can affect their nervous, circulatory, and digestive systems. Children are exposed to lead from different sources (such as paint, gasoline, and solder) and through different pathways (such as air, food, water, dust, and soil). Although all children are exposed to some lead from food, air, dust, and soil, some children are exposed to high dose sources of lead. Significant sources of lead for China's children include industrial emissions (often close to housing and schools), leaded gasoline, and occupational exposure that occurs when parents wear lead-contaminated clothing home from work, burning of coal for home heat and cooking, contaminated food, and some traditional medicines. To assess the blood lead level in children in China, a large-scale study was conducted in 19 cities among 9 provinces during 1997 to 2000. There were 6502 children, aged 3-5 years, were recruited in the study The result indicates that the mean blood lead level was 8.83ug/dl 3-5 year old living in city area. The mean blood lead level of boys was higher than that of girls (9.1l ug/dl vs 8.73ug/dl). Almost 30 percent childrens blood lead level exceeded 10ug/dl. The average blood lead level was higher than that of in 1985 (8.83ug/dl vs 8.lug/dl). An epidemiological study was carried on the children living around the cottage industries recycling the lead from battery. Nine hundreds fifty nine children, aged 5-12 years, living in lead polluted villages where the lead smelters located near the residential area and 207 control children live in unpolluted area were recruited in the study. The lead levels in air, soil, drinking water and crops were measured. The blood lead and ZnPP level were tested for all subjects. The results show that the local environment was polluted. The lead levels both in the air and crops were much higher than that of in control area. In the polluted area, the average blood level was 49.6ug/dl (rang 19.5-89.3ug/dl). Whereas, in the unpolluted area, the average blood level was 12.4ug/dl (rang 4.6-24.8ug/dl). This study indicates that in some countryside area, some cottage industries induce seriously lead pollution and cause children health problem. For the introducing of unleaded gasoline in some large cities, such as Beijing and Shanghai, the blood lead level showed a declined trend since 1997. By 2000, the use of leaded gasoline in motor vehicles has been prohibited in China. The most recent data available show that levels of lead in blood among children in Shanghai decreased from 8.3ug/dl in 1997 to 7.6ug/dl in 1999. The prevalence rate of children lead poisoning (blood lead >10ug/dl) was also decreased from 37.8% to 24.8%. In children living in downtown area, the blood lead level reduced dramatically. To explore the relationship between gene polymorphisms and individual susceptibility of lead poisoning, a molecular epidemiological study was conducted among children living in lead polluted environment. The result showed that the subjects with ALAD2 allele has higher ZPP level, and the subjects with VDR B allele has larger head circumference than only with b allele. In the present study, we demonstrated that ALAD genotypes modify lead effects on heme metabolism and VDR gene variants influence the skull development in highly exposed children. The polymorphism of ALAD and VDR genes might be the molecular inherited factor modifying the susceptibility of lead poisoning. Recently, Chinese government pays more attention to lead pollution and lead poisoning in children problem. The leaded gasoline was prohibited used in motor vehicles since 2000. The government has decided to have a clampdown on the high-polluted lead smelters for recycling the lead from battery in countryside. It is hopeful that the risk of lead poisoning in children will be decreased in the further

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4457-4463
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• 2015

Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967, $P_{heterogeneity}=0.000$; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, $P_{heterogeneity}=0.002$; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, $P_{heterogeneity}=0.000$; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857, $P_{heterogeneity}=0.000$), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897, $P_{heterogeneity}=0.001$) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, $P_{heterogeneity}=0.000$), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, $P_{heterogeneity}=0.944$; RR vs QQ: OR=2.987, 95% CI=1.861-4.795, $P_{heterogeneity}=0.350$; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796, $P_{heterogeneity}=0.824$; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, $P_{heterogeneity}=0.433$), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, $P_{heterogeneity}=0.000$) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, $P_{heterogeneity}=0.056$). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, $P_{heterogeneity}=0.000$) and dominant models (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973, $P_{heterogeneity}=0.000$) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993, $P_{heterogeneity}=0.000$) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.

• The Korean Journal of Applied Statistics
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• v.23 no.1
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• pp.113-121
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• 2010

Mixture is that DNA profiles of samples contain material from more than one contributor, especially common in rape cases. In this situation, first, the method based on enumerating a complete set of possible genotype that may have generated the mixed DNA profile have been studied for interpreting DNA mixtures. More recently, the methods utilizing peak area information to calculate likelihood ratios have been suggested. This study is concerned with the analysis and interpretation of mixed forensic stains using quantitative peak area information and the method of forensic inference for extension of material from more than or equal to three contributors. Finally, the numerical example will be outlined.

• BMB Reports
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• v.42 no.12
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• pp.834-839
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• 2009

DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation, which often occurs in CpG islands located near the regulatory regions of genes and affects transcription of specific genes. In this study, we examined the possible association of DNMT1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n = 1,100). Statistical analysis demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, showed significant association with HBV clearance in a co-dominant model (OR = 1.30, $P^{corr}$ = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, $P^{corr}$ = 0.01-0.03), respectively. These results suggest that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, might affect HBV clearance.

• Korean Journal of Head & Neck Oncology
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• v.22 no.2
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• pp.117-122
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• 2006

Background and Objectives : Thyroid carcinoma is the sixth commonest cancer in Korea and the papillary carcinoma is the most common type(88%) of the malignant thyroid tumors. Bulky DNA adducts formed by the carcinogens are repaired by DNA repair process, but failure to repair this DNA damage can cause mutations in oncogenes and tumor suppressor genes resulting in tumor formation. The xeroderma pigmentosum group C(XPC) gene is essential for this repair procedure and the XPC-PolyAT(PAT) polymorphisms may alter DNA repair capacity(DRC) and genetic susceptibility to cancer. Subjects and Methods : In a case-control study of 113 Korean patients with pathologically diagnosed thyroid papillary carcinoma and 65 control subjects, we investigated the association between the three XPC-PAT gene polymorphisms and thyroid papillary cancer susceptibility. Results : The frequency of the variant XPC-PAT allele was lower in the cases(0.349) than in the controls (0.423), but the difference was not significant(p=0.140). Using logistic regression adjusting for age and sex, risk for thyroid papillary cancer was not increased in the XPC-PAT-/+ and XPC-PAT+/+ compared to XPCPAT-/-(adjusted overall odds ratio[95% confidence intervals;95%CI]=0.52[0.26-1.03] and 0.62 [0.22-1.75], respectively; trend test, p=0.167). Conclusion : There are no relationship between the XPC-PAT polymorphism and the risk of thyroid papillary carcinoma in Korean population. Based on our results, XPC-PAT polymorphism do not modulate genetic susceptibility to thyroid papillary cancer.