Biomedical subjects

Sun-Seog Kweon

Publications and source records attributed to Sun-Seog Kweon.

12 recordsLinked to original sources

PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗

PubMed2025

Identification of MMP14 and MKLN1 as colorectal cancer susceptibility genes and drug-repositioning candidates from a genome-wide association study.

BACKGROUND: Genome-wide association studies (GWAS) and subsequent functional interpretation have been used to identify susceptible genes and potential drug-repositioning candidates. This study aimed to identify genes associated with colorectal cancer (CRC) and potential drug-repositioning candidates. METHODS: Patients with CRC at Seoul National University Hospital (SNUH, discovery study) and Chonnam National University Hospital (CNUH, replication study) were included as case groups. The Korean Genome and Epidemiology Study (KoGES) participants were included as a control group. Single-nucleotide polymorphisms (SNPs) were extracted from blood-derived DNA (N = 409,063). A SNP-based logistic regression model was applied. Furthermore, post-GWAS analysis was conducted. Drug-repositioning candidates were identified using a pre-trained deep neural network and the druggability assessment tool. RESULTS: In the discovery study, we conducted a 1:3 age- and sex-matched case-control study that included 500 CRC cases (mean age 63.0 ± 7.15 years) and 1,500 healthy controls (mean age 62.9 ± 7.07 years), each group comprising 50% males and 50% females. The replication study enrolled 4,860 patients with CRC and 46,384 healthy controls. The two-stage GWAS revealed statistically significant associations among MKLN1 (rs75170436, 7q32.3, beta (log odds ratio) = - 0.90, Pmeta = 5.90 × 10-13), MMP14 (rs3751489, 14q11.2, beta (log odds ratio) = - 1.91, Pmeta = 2.31 × 10-12). Post-GWAS functional analysis revealed strong associations on two genes highlighting deleterious effects and increased gene expression. Drug-repositioning analysis identified GW0742 (PPARβ/δ agonist) with the highest binding score and druggability score for MMP14 with a reference allele (12.06, 0.85). CONCLUSIONS: Using GWAS, MKLN1 and MMP14 were found to be associated with CRC development and we identified GW0742 (PPARβ/δ agonist) as a potential drug-repositioning candidate for CRC based on MKLN1 and MMP14. These findings improve the understanding of CRC development and provide insights into novel therapeutic targets and candidates for CRC treatment.

Humans↗

PubMed2006

Seroprevalence and risk factors for hepatitis C virus infection among female commercial sex workers in South Korea who are not intravenous drug users.

Several previous studies have reported a high prevalence of hepatitis C virus (HCV) infection among commercial sex workers (CSWs), but the situation is often compounded by coexisting factors, such as intravenous drug use. We conducted a seroepidemiologic study of 1,527 female CSWs in South Korea. All participants tested negative for human immunodeficiency virus and were not illicit intravenous drug users (IDUs). Twenty-one participants (1.4%) were positive for antibodies to HCV. According to the multivariate logistic regression analysis, a history of acupuncture and diabetes mellitus were associated with the seroprevalence of HCV, whereas time spent as a CSW showed only borderline significance. Sexual activity was not an independent predictor of increased risk for HCV infection in female CSWs who had never been illicit IDUs.

Adult↗

PubMed2006

[Associations between carotid intima-media thickness, plaque and cardiovascular risk factors].

OBJECTIVES: This study was conducted to examine the association between the carotid artery intima-media thickness (IMT), plaque and cardiovascular risk factors according to gender and age. METHODS: The data used for this study were obtained from 1,507 subjects (691 men, 816 women), aged 20-74 years, who participated in 'Prevalence study of thyroid diseases' in two counties of Jeollanam-do Province during July and August of 2004. The body mass index (BMI) and waist hip ratio (WHR) were calculated by anthropometry. The blood pressure, pulse rate, pulse pressure, total cholesterol, triglyceride, HDL cholesterol and fasting blood sugar level were also measured. Ultrasonography was used to measure the carotid artery IMT and plaque. IMT measurements were performed at 6 sites, including both common carotid arteries, and the bulb and internal carotid arteries. The definition of the 'mean IMT' was mean value obtained from these 6 sites. RESULTS: The mean+/- standard deviation IMT values were 0.65+/-0.14 and 0.60+/-0.13 mm in men and women (p<0.001), respectively. The data were analyzed according to gender and the 50 year age groups. In a multiple linear regression analysis, age and hypertension were positively associated with the mean IMT in both men and women, aged<50 years. Age, total cholesterol and smoking (current) were positively associated with the mean IMT in men (-50 years). Age was positively associated with the mean IMT in women (> or = 50 years), but the HDL cholesterol level was negatively associated. The prevalence of plaques was 44.2%(196/443) in men and 19.4%(89/459) in women, for those greater than 50 years of age. In a multiple logistic regression analysis, age (OR=1.090, 95%CI=1.053-1.129), HDL cholesterol (OR=0.964, 95%CI=0.944-0.984), total cholesterol (OR=1.009, 95%CI=1.002-1.017)and BMI (OR=0.896, 95%CI=0.8180.983) were independently associated with plaques in men; whereas, age (OR=1.057, 95%CI=1.012-1.103), HDL cholesterol (OR=0.959, 95%CI=0.932-0.986), pulse pressure (OR=1.029, 95%CI=1.007-1.050) and triglycerides (OR=0.531, 95%Cl=0.300-0.941) were independently associated with plaques in women. CONCLUSIONS: There were significant gender and aging differences in the association between the IMT, plaque and cardiovascular risk factors. Therefore, for the prevention of atherosclerosis, selective approaches should be considered with regard to gender and age factors.

Adult↗

PubMed2005

Association between bone mineral densities and serum lipid profiles of pre- and post-menopausal rural women in South Korea.

The objectives of this population-based study were to investigate the potential association between bone mineral density (BMD) and serum lipid profiles and to compare the effects of serum lipids on BMD at various skeletal sites in pre- and post-menopausal women. In July and August of 2004, BMD was measured at a variety of skeletal sites [lumbar spine (L1-4), femoral neck, trochanter, Ward's triangle, shaft and proximal total hip] using the GE/Bravo Lunar DPX dual-energy X-ray absorptiometer in a South Korean population-based sample of 375 pre-menopausal and 355 post-menopausal rural women aged 19-80 years. The levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were inversely associated with BMD in both pre- and post-menopausal women. In the pre-menopausal women, correlations were shown only for lumbar 1-4 (TC: r=-0.12, P<0.05; LDL-C: r=-0.12, P<0.05), whereas in the post-menopausal women, no correlation was evident for the lumbar sites. In the post-menopausal subjects, the TC levels showed significant correlations with the BMD values at the trochanter (r=-0.15, P<0.01), shaft (r=-0.16, P<0.001) and proximal total hip (r=-0.15, P<0.01) sites, while the LDL-C levels showed significant correlations with the BMD values at the neck (r=-0.13, P<0.05), trochanter (r=-0.21, P<.001), shaft (r=-0.20, P<0.001) and proximal total hip (r=-0.20, P<0.001) sites. The levels of triglyceride (TG) were shown to have a significant positive correlation with BMD values at the trochanter site (r=0.11, P=0.05) in the post-menopausal women; by contrast, subjects in a higher quartile of TG levels show lower lumbar BMD values in the pre-menopausal women. The levels of high-density lipoprotein cholesterol (HDL-C) were not associated with BMD values at any of the sites in the pre- and post-menopausal subjects. Our data indicate a relationship between BMD values and serum lipid levels and suggest differences between pre- and post-menopausal women in terms of the effects of serum lipids on BMD at various skeletal sites.

Absorptiometry, Photon↗

PubMed2005

Does arm length indicate cognitive and functional reserve?

BACKGROUND: This study aimed to examine whether arm length and height were associated with cognitive and functional abilities. METHODS: Screening interviews were conducted in 235 community dwelling individuals aged 65 and over. The assessment scales included the Korean version of modified Mini-Mental State Examination (K-mMMSE) for cognition, and the Korean Instrumental Activities of Daily Living (K-IADL) for functional ability. All the participants were examined clinically and a diagnosis of dementia was ascertained. Anthropometric measurements included total arm span and height. RESULTS: Both arm length and height correlated significantly with the cognitive and functional scales. In the multivariate regression models, their associations were significant, independent of age, sex, education, and other variables. Shorter arm length was also significantly associated with dementia; while, height lost significance after an adjustment for the potential confounders. CONCLUSIONS: Arm length and height could indicate cognitive and functional ability. Arm length, which was known to be less prone to degenerative processes, might be more stable as an indicator for cognitive and functional reserve capacity than height.

Activities of Daily Living↗

PubMed2005

Association of estrogen receptor-alpha gene polymorphisms with bone mineral density in postmenopausal Korean women.

We examined the potential associations between PvuII and XbaI polymorphisms in the first intron of the estrogen receptor alpha (ER-alpha) gene and bone mineral density (BMD) in a population-based study of 174 postmenopausal Korean women. BMD was measured at the lumbar spine (L2-L4), right femoral neck, right trochanter, and right Ward's triangle. ER-alpha gene polymorphisms were detected by PvuII and XbaI restriction endonuclease digestion of polymerase chain reaction products. Differences in BMD values between the ER-alpha genotypes were analyzed in a general linear model, with adjustments for age, height, weight, and smoking status. The following genotype frequencies were noted: PP, 14.9%; Pp, 46.0%; pp, 39.1%; XX, 3.5%; Xx, 29.3%; and xx, 67.2%. Both the femoral neck and Ward's triangle BMD values in women with the Pp genotype were significantly (P < 0.05) higher than those in women with the pp genotype. No significant effect of the XbaI genotype on BMD was found at any site. Carriers of the pX haplotype were more likely to have lower BMD values at the trochanter than noncarriers, after adjustment for potentially confounding factors. Women with the pp genotype had more previous hip or spine fractures than those with other genotypes (P = 0.05). These results suggest that the PvuII polymorphism and the ER-alpha haplotype may be associated with the BMD at several femur sites in postmenopausal Korean women.

Aged↗

PubMed2005

Does waist indicate dyslipidemia better than BMI in Korean adult population?

Obesity is an independent and modifiable risk factor for cardiovascular disease, and known as a core of the metabolic syndrome. Obesity has been largely diagnosed based upon anthrompometric measurements like waist circumference (WC) and body mass index (BMI). We sought to determine associations between anthropometric measurements and dyslipidemia in a community adult sample composed of 1,032 community residents (356 men, 676 women) aged 50 yr and over in Namwon, Korea. Blood tests for lipid profiles, including total cholesterol (TC) and HDL cholesterol (HDL) were performed, and dyslipidemia was defined as TC/HDL greater than 4. Anthropometric measurements included WC, waist-to-height ratio (WHtR), waist-to-hip ratio, and BMI. All anthropometric measures were categorized into quartiles and evaluated for associations with dyslipidemia. TC/HDL showed the significant associations with the anthropometric measures, independently of potential confounders. In women, increases of obesity indexes by quartile analyses showed linear increases of odds ratios for dyslipidemia (p values <0.01 by trend test). In men, except BMI, same patterns of association were noted. WC and WHtR were significantly associated with dyslipidemia in Korean adult population. As a simple and non-invasive method for a detection of obesity and dyslipidemia, anthropometric measurements could be efficiently used in clinical and epidemiologic fields.

Adult↗

PubMed2005

The effect of apolipoprotein E polymorphism on lipid levels in Korean adults.

The aim of this study was to determine the effects of polymorphisms in the apolipoprotein E gene (APOE) on lipid levels in Korean adults and to investigate the interactions between these polymorphisms and environmental factors in determining lipid levels. We performed a cross-sectional study of 1,900 subjects (668 men and 1,232 women; 45-74 yr old) in Namwon, Korea, in 2004. APOE polymorphisms were determined by polymerase chain reaction and restriction enzyme analysis. Carriers of the APOE*E2 (E2) allele had significantly lower total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations than did carriers of the APOE*E3 (E3) or APOE*E4 (E4) alleles, regardless of gender. The APOE allele type had significant effect on high-density lipoprotein cholesterol (HDL-C) and triglyceride levels in women, but not in men. The effect of APOE allele type on HDL-C levels was modified by age in women. In addition, in men, the effect of APOE allele type on triglyceride levels was modified by smoking. These findings highlight the important effect of gene-environment interactions on lipid levels.

Aged↗

PubMed2005

Distribution of the ankle-brachial index and associated cardiovascular risk factors in a population of middle-aged and elderly koreans.

The Doppler ankle-brachial pressure index (ABI) is an objective and efficient tool that can be used to determine the presence and severity of peripheral arterial disease in the lower extremities. The ABI value is inversely associated with other cardiovascular risk factors. To date, there have been no studies of the distribution of ABI in Korea. We performed a cross-sectional study of 1,943 subjects (681 men and 1,262 women; 45-74 yr old) in Namwon, Korea. The prevalence of a low ABI (<0.90) was 2.2% in men and 1.8% in women, and a high ABI (>or=1.30) was prevalent in 3.1% of men and 0.8% of women. Age, smoking habits, waist circumference, hypertension, and blood pressure were associated with ABI values in both sexes. The presence of carotid plaques was associated with ABI values only in men, whereas pulse pressure was associated with ABI values only in women (p<0.05). Although the prevalence of a low ABI in the present study was lower than those reported previously for Western populations and Japanese men, our results suggest that the ABI might be used as an indicator of cardiovascular risk factors in adult Koreans.

Aged↗

PubMed2005

Quantitative ultrasound of the calcaneus in a Korean population: reference data and relationship to bone mineral density determined by peripheral dual X-ray absorptiometry.

The aim of this study was to establish reference data for the quantitative ultrasound (QUS) of the calcaneus and for the bone mineral densities (BMD) of the calcaneus and distal forearm, and to evaluate the correlation between QUS parameters and BMD in a Korean population. We performed a cross-sectional study involving 3,053 subjects (1,225 men and 1,828 women). QUS was conducted on the calcaneus and was quantified as speed of sound (SOS, m/sec), broadband ultrasound attenuation (BUA, dB/MHz), and stiffness index. The BMD of the calcaneus and distal forearm were measured using dual X-ray absorptiometry. The peak mean values for the QUS parameters occurred in the 20 to 29-yr-old subjects of both sexes, with the exception of the BUA, which reached the highest values in women of 30-39 yr. For both sexes, the mean BMD of the calcaneus was highest in those 20-29 yr old and that of the distal forearm was highest in those 40-49 yr old. The correlations between the QUS and BMD results were found to be 0.41 to 0.73 in men and 0.51 to 0.76 in women. Theses data can serve as a reference values for both sexes in Korea.

Absorptiometry, Photon↗

PubMed2004

Alpha-adducin Gly460Trp polymorphism and essential hypertension in Korea.

Previous studies have suggested that the Gly460Trp polymorphism of the alpha-adducin gene (ADD-1) is associated with salt sensitivity and primary hypertension. The results of linkage or association studies of ADD-1 of different populations are controversial. This study investigated the relationship between the Gly460Trp polymorphism of ADD-1 and essential hypertension in a Korean population. The subjects (n=903) were participants in a population-based study in Jangseong County, Korea. The Gly460Trp polymorphism of ADD-1 was determined using a polymerase chain reaction method. The frequency of the 460Trp allele was 59.4% in normotensives and 61.1% in hypertensives (p=0.523). The frequencies of the genotypes did not differ significantly between the hypertensive and normotensive groups (16.3% Gly/Gly, 45.8% Gly/Trp, and 38.0% Trp/Trp in normotensives; 16.2% Gly/Gly, 45.8% Gly/Trp, and 38.0% Trp/Trp in hypertensives; p=0.928). After adjusting for other risk factors, Gly/Trp and Trp/Trp were not associated with hypertension (OR 1.00, 95% CI 0.65-1.53, Gly/Trp vs. Gly/Gly; OR 1.22, 95% CI 0.79-1.90, Trp/Trp vs. Gly/Gly). These findings suggest that the Gly460Trp polymorphism of ADD-1 is not associated with hypertension.

Calmodulin-Binding Proteins↗