• Genomics & Informatics
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• v.10 no.3
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• pp.184-193
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• 2012

Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index ${\geq}25kg/m^2$), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.

• Genomics & Informatics
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• v.5 no.4
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• pp.161-167
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• 2007

Glucuronidation by the uridine diphosphateglucuronosy-ltransferase 1A enzymes (UGT1As) is a major pathway for elimination of particular drugs and endogenous substances, such as bilirubin. We examined the relation of eight single nucleotide polymorphisms (SNPs) and haplotypes of the UGT1A gene with their clinical factors. For association analysis, we genotyped the variants by direct sequencing analysis and polymerase chain reaction (PCR) in 218 healthy Koreans. The frequency of UGT1A1 polymorphisms, -3279T>G, -3156G>A, -53 $(TA)_{6>7}$, 211G>A, and 686C>A, was 0.26, 0.12, 0.08, 0.15, and 0.01, respectively. The frequency of -118 $(T)_{9>10}$ of UGT1A9 was 0.62, which was significantly higher than that in Caucasians (0.39). Neither the -2152C>T nor the -275T>A polymorphism was observed in Koreans or other Asians in comparison with Caucasians. The -3156G>A and -53 $(TA)_{6>7}$ polymorphisms of UGT1A were significantly associated with platelet count and total bilirubin level (p=0.01, p=0.01, respectively). Additionally, total bilirubin level was positively correlated with occurrence of the UGT1A9-118 $(T)_{9>10}$ rare variant. Common haplotypes encompassing six UGT1A polymorphisms were significantly associated with total bilirubin level (p=0.01). Taken together, we suggest that determination of the UGT1A1 and UGT1A9 genotypes is clinically useful for predicting the efficacy and serious toxicities of particular drugs requiring glucuronidation.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Tuberculosis and Respiratory Diseases
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• v.76 no.6
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• pp.269-275
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• 2014

Background: The six-minute walk test has been widely used in people with chronic cardiopulmonary disorders as an outcome assessment with regards to therapeutic or prognostic determinants. This study was undertaken to determine the six-minute walk distance (6MWD) in a sample of healthy Koreans and to create a reference equation. We also compared the 6MWD of our cohort with previously published equations. Methods: Two hundred fifty-nine healthy subjects (95 males) aged 22-59 years performed two walking tests using a standardized protocol. 6MWD was defined as the greatest distance achieved from the two tests. The effect of anthropometrics on the 6MWD was also investigated. Results: The average 6MWD was $598.5{\pm}57.92m$, with significantly longer distances by males ($628.9{\pm}59.51m$) than females ($580.9{\pm}47.80m$) (p<0.001). Age, height, weight, and body mass index were significantly correlated with 6MWD in univariate analysis. Stepwise multiple regression showed height to be single independent predictor of 6MWD ($r^2$=0.205, p<0.001). The reference equations derived in Caucasian and North African populations tend to overestimate the distance walked by Korean subjects, while Asian equations underestimate it. Conclusion: The average 6MWD in these Korean populations was 600 m. The regression equation revealed that individual's height was the most significant predictor of distance, explaining 20.5% of the distance variance.

• Clinical Nutrition Research
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• v.6 no.3
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• pp.172-182
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• 2017

We investigated the association between dietary habits/food group consumption patterns and early risk of metabolic syndrome (MetS), a main cause for metabolic disease. Study participants were recruited from the health promotion center in Dong-A University Hospital and public advertisement. Study subjects (n = 243, 21-80 years) were categorized into three groups: Super-healthy (MetS risk factor [MetS RF] = 0, n = 111), MetS-risk carriers (MetS RF = 1-2, n = 96), and MetS (MetS $RF{\geq}3$, n = 27). Higher regularity in dietary habits (breakfast-everyday, regular eating time, non-frequent overeating, and non-frequent eating-out) was observed in the Super-healthy group than in the MetS-risk carriers, and particularly in the MetS subjects. The relationship between food group consumption patterns and MetS-risk related parameters were investigated with adjustment for confounding factors. Fruit consumption was positively associated with HDL-cholesterol, and tended to be negatively associated with waist circumference, triglyceride, LDL-cholesterol, and insulin resistance (IR). The consumption of low-fat meats and fish, and vegetables was negatively associated with hs-CRP. Specifically, the consumption of seafoods belonging to the low-fat fish was negatively associated with fasting glucose, hs-CRP, and interleukin (IL)-6. Anchovy/dried white baits consumption was negatively associated with fasting insulin and IR. Green-yellow vegetables consumption was negatively associated with fasting insulin, IR, and hs-CRP. On the other hand, sugars and fast-foods were positively associated with LDL-cholesterol. Additionally, fast-foods consumption was positively associated with hs-CRP and IL-6 levels. In conclusion, dietary habits/food group consumption patterns are closely associated with MetS-risk related parameters in Koreans. It may suggest useful information to educate people to properly select healthy foods for early prevention of MetS.

• Journal of Yeungnam Medical Science
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• v.39 no.3
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• pp.230-234
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• 2022

Background: To date, there have been no studies on the normal anatomic values of the anal sphincter in healthy Koreans. Therefore, this study aimed to determine the normal anatomic values of transanal ultrasonography (TAUS). Methods: The thickness of the external anal sphincter (EAS) and internal anal sphincter (IAS) was measured by TAUS from healthy Korean volunteers between September 2019 and August 2021. Results: Thirty-six volunteers with a median age of 37 years (range, 20-77 years) and a median body mass index (BMI) of 23.5 kg/m² (range, 17.2-31.2 kg/m²) were examined. The median thickness of the EAS at 4 cm and 2 cm from the anal verge was 7.4 mm (range, 5.8-8.8 mm) and 6.5 mm (range, 5.6-8.0 mm), respectively. The median thickness of the IAS at 2 cm from the anal verge was 1.8 mm (range, 0.8-4.3 mm). There were no differences in sphincter muscle thickness between the sexes. However, the EAS tended to thicken as the BMI increased (EAS at 2 cm and 4 cm from the anal verge, Spearman rho=0.433, 0.363; p=0.008 and p=0.029, respectively). Conclusion: In healthy Korean, the median thickness of the IAS at 2 cm from the anal verge was 1.8 mm and the median thickness of the EAS at 2 cm and 4 cm from the anal verge was 6.5 mm and 7.4 mm respectively. There were no differences in anal sphincter thickness between sexes, but BMI was related to EAS thickness.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.65-72
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• 2012

Antidepressants are frequently prescribed for a wide range of symptoms. Surveys in several countries have suggested that negative attitudes towards antidepressants are common. However, there has been limited research associated with the attitudes in Korea. Therefore, this quantitative descriptive study describing the perception and attitudes toward antidepressants was performed using healthy people and outpatients who are not taking antidepressants. The surveys by means of self-reporting questionnaires showed negative attitudes towards antidepressants (74.2%). But, 74.2% of above participants gave positive answers to take antidepressants when they are counseled by medical professionals. Higher rates of negative attitudes were found in younger age group ("it causes addiction") and healthy volunteers and urban area groups ("it causes physical harm"). Study participants without experiences in taking antidepressants showed more negative attitudes although the difference was not statistically significant. Based on the results, accurate and objective information about antidepressants needs to be provided by well-trained health professionals.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.177-177
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• 2003

Adult periodontitis is a chronic inflammatory disease whose etiology is not well defined. Recent studies have shown that vitamin D receptor gene has been a candidate for the susceptibility of adult periodontitis. The purpose of this study is to investigate the frequency of Taq I restriction fragment length polymorphism (RELP) in the vitamin D receptor gene in 141 periodontically healthy controls and 32 adult periodontitis patients. Taq I RFLP in the vitamin D receptor gene were detected by PCR amplification, followed by restriction enzyme digestion and 2% agarose gel electrophoresis. There were no significant difference in the distribution of Taq I RFLP between healthy controls and adult periodontitis group (P > 0.05). Thus, Taq I RFLP in the vitamin D receptor gene may not confer the susceptibility to adult periodontitis in Korean population. However, t allele distributions of this RFLP showed various frequencies among ethnic groups studied. Further studies in other ethnic groups will be required.

• Women's Health Nursing
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• v.4 no.2
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• pp.245-257
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• 1998

The characteristics of health behavior related pregnancy and childbirth have reflected on the cultural belief and value in the society. The efforts for women's health promotion through the current illumination of the traditional health care are the prompting assignment to be in nursing. The process of motherhood already progress before the motherhood actually. The functional state as the expectant mother can be the important predicting factor of the postpartum state, the quality of a married life. Motherhood was analyzed by Walker and Avant's method to clarify the concept 'to be a mother' using the various concepts like Koreans' Taekyo, transition to motherhood, maternal identity, maternal role attainment, maternal fetal attachment, and maternal fetal interaction. Upon the concept analysis, naturalness, responsibility, attachment, readiness, controllability were identified as the defining characteristics of motherhood. The antecedents of motherhood were consist of maternal affection, positive self esteem, pregnancy acceptance, fetus recognition and the consequences of motherhood were consist of positive maternal identity, maternal fetal attachment, confidence about the maternal role, the healthy mother and the healthy baby. The empirical referents of motherhood were consists of recognition of motherhood, expectation about motherhood, fetal recognition with ultrasonography and fetal movement, experience of unification between mother and fetus, expression of affection to the fetus, concern about fetal health, concern and practice about Taekyo, adaptation behavior about physical change and discomfort due to pregnancy. Therefore it is necessary to develop the instruction program of motherhood including the defining attributes identified in this study.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.242-247
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• 2002

Background: Tumor necrosis factor-alpha (TNF-$\alpha$) is known to play an important role in various conditions such as inflammation, autoimmunity, apoptosis, insulin resistance and sleep induction. Five single nucleotide polymorphisms (SNPs) have been known to affect the transcriptional activities of TNF-$\alpha$: -1,031T/C, -863C/A, -857C/T, -308G/A and -238G/A. Methods: We have investigated 5 SNPs of the promoter region of TNF-$\alpha$ gene, the distribution of 5-locus TNF-$\alpha$ haplotypes, and their haplotypic associations with previously typed HLA-A, -B and -DRB1 loci in 107 healthy unrelated Koreans. TNF-$\alpha$ SNPs were typed using PCR-single-strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. Results: The allele frequencies of -1,031C, -863A, -857T, -308A, and-238A, which are known as the high-producer-type, were 19.3%, 15.9%, 14.0%, 5.9%, and 2.9%, respectively. The frequency of -308A allele, known to be associated with autoimmune diseases, was 5.9% in Koreans which was lower than Caucasians (14~17%) and somewhat higher than Japanese (1.7%). Five most common TNF-$\alpha$ haplotypes (-1,031/-863/-857/-308/-238) comprised over 95% of total haplotypes: TCCGG (58.4%), CACGG (14.8%), TCTGG (13.7%), TCCAG (5.3%), and CCCGA (3.1%). Strong positive associations (P<0.001) were observed between TCCGG and B62; between CACGG and B51, $DRB1^*0901$; between TCTGG and B35, B54, B59, $DRB1^*1201$; and between TCCAG and A33, B58, $DRB1^*0301$, $DRB1^*1302$. Five most common extended haplotypes (>3%) comprised around 16% of total haplotypes: A33-B58-TCCAG-$DRB1^*1302$, A24-B52-TCCGG-$DRB1^*1502$, A33-B44-TCCGG-$DRB1^*1302$, A24-B7-TCCGG-$DRB1^*0101$, and A11-B62-TCCGG-$DRB1^*0406$. The distribution of extended HLA and TNF-$\alpha$ haplotypes showed that most of HLA haplotypes were almost exclusively associated with particular TNF-$\alpha$ haplotypes. Conclusion: The results obtained in this study would be useful as basic data for anthropologic studies and disease association studies in Koreans.