ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.

ATPase inhibitory factor 1 (IF1) is an ATP synthase-interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up-regulated in response to electrical pulse stimulation of skeletal muscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake via AMPK in skeletal muscle cells and primary cultured myoblasts. Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1-mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down-regulated blood glucose level. In addition, IF1 inhibits ATP hydrolysis by ß-F1-ATPase in plasma membrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose a mechanism by which AMPK and Akt contribute independently to IF1-mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.-Lee, H. J., Moon, J., Chung, I., Chung, J. H., Park, C., Lee, J. O., Han, J. A., Kang, M. J., Yoo, E. H., Kwak, S.-Y., Jo, G., Park, W., Park, J., Kim, K. M., Lim, S., Ngoei, K. R. W., Ling, N. X. Y., Oakhill, J. S., Galic, S., Murray-Segal, L., Kemp, B. E., Mantzoros, C. S., Krauss, R. M., Shin, M.-J., Kim, H. S. ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.

Medium-Chain Acylcarnitines Are Associated With Cardioembolic Stroke and Stroke Recurrence.

Objective- Stroke is a heterogeneous disease with diverse causes, which affect the risk of recurrence. This study aimed to identify novel biomarkers that are clinically relevant to the diagnosis of cardioembolic stroke (CE) and the prediction of stroke recurrence using metabolomics. Approach and Results- We obtained blood samples and clinical data from a consecutively registered, hospital-based acute stroke registry and from healthy controls. Mass-spectrometry-based profiling was performed, and several metabolomic signatures were selected for the discrimination of CE and stroke recurrence, coupled with multivariate statistical analysis. Finally, 190 acute ischemic stroke participants (43 CE patients and 147 non-CE patients) and 30 control participants were included. We obtained 29 metabolomics signatures, and of these, 2 medium-chain acylcarnitines (decanoylcarnitine and octanoylcarnitine) were selected as independent discriminants for CE (odds ratio, 2.839; 95% CI, 1.241-6.493 for decanoylcarnitine; odds ratio, 2.839; 95% CI, 1.241-6.493 for octanoylcarnitine). Elevated medium-chain acylcarnitines were also associated with a higher risk of stroke recurrence (hazard ratio, 3.767; 95% CI, 1.276-11.117 for decanoylcarnitine; hazard ratio, 5.519; 95% CI, 1.22-18.781 for octanoylcarnitine). The levels of decanoylcarnitine and octanoylcarnitine were correlated as known surrogate markers of CE. The levels of decanoylcarnitine and octanoylcarnitine were significantly higher in stroke patients with a high-risk potential of cardioembolism than in those with low or intermediate risk. Conclusions- Metabolomics provided an improved understanding of CE pathogenesis and stroke recurrence. We have identified decanoylcarnitine and octanoylcarnitine as novel biomarkers for CE and stroke recurrence.

Association between sugar-sweetened beverage consumption and incident hypertension in Korean adults: a prospective study.

PURPOSE: Epidemiological information on the association between sugar-sweetened beverage (SSB) consumption and the risk for hypertension (HTN) in Koreans is very limited. We tested the hypothesis that increased SSB consumption is related to a higher risk of HTN among middle-aged Korean adults in a Korean community-based cohort. METHODS: From participants of the cohort from 2001 to 2010, we selected 5775 subjects without HTN, diabetes, cardiovascular disease, and cancer and who had no information on dietary assessment at baseline. To assess the relationship between SSB consumption and HTN, we estimated hazard ratios (HRs) and 95% confidence intervals using Cox regression analysis. In addition, stratified analysis by body mass index (BMI) was conducted. RESULTS: During the follow-up, we identified 1175 cases of incident HTN. The adjusted HR of HTN for the highest quartile of SSB consumption was 1.21 compared to the lowest quartile. Furthermore, higher consumption of SSB was significantly associated with increased incidence of HTN in subjects with BMI ≥ 25 kg/m2, whereas there was no significant association among subjects with BMI < 25 kg/m2. CONCLUSIONS: The results of this study suggest that SSB consumption was associated with an increased risk of HTN, particularly among obese participants.

Association among genetic variants in the vitamin D pathway and circulating 25-hydroxyvitamin D levels in Korean adults: results from the Korea National Health and Nutrition Examination Survey 2011-2012.

Vitamin D deficiency affects >60% of the Korean population. Recent reports in Caucasian, African American, and Chinese populations indicate an association between vitamin D status and related single nucleotide polymorphisms (SNPs), but specific associations differ among study populations. We investigated the relationship between five SNPs involved in the vitamin D metabolic pathway (DHCR7 rs12785878, GC rs2282679, CYP2R1 rs12794714, CYP2R1 rs10741657, and CYP24A1 rs6013897) and serum 25-hydroxyvitamin D [25(OH)D] status in Koreans using the Korea National Health and Nutrition Examination Survey, a nationwide database. Whether the association was modified by demographic and lifestyle factors, including sex, body mass index (BMI), smoking status, drinking status, physical activity, and sun exposure, were also investigated. The results showed the serum level of 25(OH)D was associated with rs12785878, rs2282679, and rs12794714 genotypes, but not with rs10741657 or rs6013897. The genetic risk score (GRS) calculated by summing the number of alleles of these 5 SNPs was associated with low circulating levels of 25(OH)D. However, the negative association between 25(OH)D and GRS was modified by obesity and sun exposure. Specifically, negative associations between 25(OH)D and GRS were present in adults with lower BMI (<25 kg/m2) and longer sun exposure time (≥2 h/day). In conclusion, common variants of vitamin D-related SNPs are associated with vitamin D status in Koreans, and this genetic effect was masked when BMI ≥25 kg/m2 or sun exposure <2 h/day. Additionally, seasonal variation must be considered in future studies among Koreans.

Association of dietary intakes of total and subtypes of fat substituted for carbohydrate with metabolic syndrome in Koreans.

Amount of fat consumption has gradually increased among Koreans, which is relatively lower than western countries. In the current study, we examined the association between dietary fat and metabolic syndrome (MetS) prevalence among Korean adults. 3,212 participants who are aged 30-74 years from the Korea National Health and Nutritional Examination Survey (KNHANES) VI (2013) were included for cross-sectional analyses. Dietary intake data was assessed using 24-hour recall method, and MetS was defined using guideline of the National Cholesterol Education Program Adult Treatment panel III (NCEP-ATP III). Multivariate logistic regression analysis was used to estimate MetS odds ratios, using nutrient density model, according to 5% percent unit of dietary fat intake. The prevalence of MetS was significantly associated with dietary intake of total fat and saturated fatty acid (SFA) after adjustment (odds ratio [OR] 0.984 95% confidence interval [CI] 0.972-0.996; OR 0.946 95% CI 0.915-0.979). When dietary intake of total fat and SFA were substituted for carbohydrate (CHO), ORs for MetS were 0.985 (95% CI 0.972-0.998) and 0.948 (95% CI 0.907-0.990), respectively, after adjusting for potential covariates. In summary, MetS was significantly associated with dietary intakes of total fat and SFA, and when substituting dietary fat for carbohydrate among Koreans.

The Association between Advanced Liver Fibrosis and Mortality Is Modified by Dietary Quality among Korean Adults: Results from the Korea National Health and Nutrition Examination Survey with Mortality Data.

Advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality; however, an independent association of liver fibrosis with mortality is not well defined. We aimed to investigate the association between advanced liver fibrosis and all-cause and cardiovascular mortality and the mediation effect of diet quality. We analyzed 35,531 participants with suspected NAFLD, excluding competing etiologies of chronic liver disease, from the Korea National Health and Nutrition Examination Survey 2007-2015, and followed up until 31 December 2019. The severity of liver fibrosis was assessed using the NAFLD fibrosis score (NFS) and the fibrosis-4 index (FIB-4). The Cox proportional hazards model was used to examine the association of advanced liver fibrosis with mortality. During a mean 8.1 years of follow-up, 3426 deaths occurred. Advanced liver fibrosis determined by NFS and FIB-4 was associated with increased risks of all-cause and cardiovascular mortality after adjusting for confounders. When NFS and FIB-4 were combined, the high NFS + high FIB-4 group was significantly associated with higher risks of all-cause mortality (hazard ratio [HR] 1.85, 95% CI 1.42-2.43) and cardiovascular mortality (HR 2.04, 95% CI 1.23-3.39), respectively, compared with the low NFS + low FIB-4 group. However, these associations were attenuated in people with high diet quality. Advanced liver fibrosis is an independent risk factor for all-cause and cardiovascular mortality in people with NAFLD, and the association between advanced liver fibrosis and mortality is modified by a high-quality diet.

Trends in Diet Quality and Cardiometabolic Risk Factors Among Korean Adults, 2007-2018.

Importance: Few studies have examined the dietary trends in Korea beyond evaluating selected food groups. To help prevent cardiometabolic disease burdens, a comprehensive investigation of the trends in overall diet quality and identification of possible contributing factors would be useful. Objective: To investigate the trends and independent associations of age, period, and birth cohort with diet quality and cardiometabolic risk factors among Korean adults. Design, Setting, and Participants: Serial cross-sectional and age-period-cohort analyses were conducted of nationally representative 24-hour dietary recall data from the Korea National Health and Nutrition Examination Survey 2007-2018. The study population included 65 416 Korean adults aged 19 to 79 years. Data analyses were conducted from March 1, 2020, through April 30, 2021. Exposures: Age, calendar year, birth cohort, and population sociodemographic characteristics. Main Outcomes and Measures: Korean Healthy Eating Index (KHEI), a validated diet quality score (range, 0-90, with higher scores indicating greater diet quality), and 8 cardiometabolic risk factors (waist circumference and systolic blood pressure, diastolic blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and fasting blood glucose levels). Results: Among 65 416 participants, mean age (SD) was 44.5 (0.1) years and 36 631 were women (55.8%). In 2007-2018, the age-standardized mean (SE) KHEI score increased from 51.0 (0.4) to 52.1 (0.5), which was associated with reduced sodium intake and increased whole grain, dairy, and protein-rich food intakes. The mean (SE) KHEI score was lowest at age 39 years (50.1 [0.3]) and increased at older ages (58.0 [0.3] at 79 years). Controlling for age and period effects, the highest KHEI score was observed among the birth cohorts of 1960-1964 (53.6 [0.9]) and decreased in subsequent cohorts (45.5 [1.2] in the 1990-1999 birth cohort). Similar cohort effects in cardiometabolic risk factors were observed, showing the lowest waist circumference, blood pressure, and total cholesterol levels among the birth cohorts of the 1960s and 1970s and higher levels among more recent birth cohorts (1990-1999 vs 1960-1964: waist circumference, 83.8 [0.5] vs 81.4 [0.4] cm; systolic blood pressure, 118.7 [0.7] vs 116.4 [0.4] mm Hg; total cholesterol, 200.2 [0.9] vs 198.9 [0.7] mg/dL). At most ages, periods, and birth cohorts, the mean KHEI score was consistently higher in adults living in urban areas (at age 45 years: 50.5 [1.0] vs 49.7 [0.9] rural) and among high-income (at age 45 years: 50.7 [1.1] vs 49.3 [0.9] low income) and educational levels (at age 45 years: 53.1 [0.9] vs 49.1 [1.0] low educational level). Conclusions and Relevance: The findings of this study suggest that, from 2007 to 2018, the diet quality of Korean adults modestly improved. Despite the improvement, inequalities in diet among age, birth cohort, and socioeconomic subgroups persisted, suggesting that more intense interventions may be needed to target the susceptible groups.

Gender and tobacco epidemic in South Korea: implications from age-period-cohort analysis and the DPSEEA framework.

OBJECTIVES: To understand a 20-year trend of gender-specific smoking prevalence among adults in South Korea. DESIGN: Age-period-cohort analysis using the intrinsic estimator method was applied to examine the separate contribution of age, period and cohort effect on smoking prevalence. The Driving Force-Pressure-State-Exposure-Effect-Action (DPSEEA) framework was used to explain the observed smoking trends by mapping potential determinants and to address policy implications. SETTING: General adult population in South Korea. PARTICIPANTS: 34 828 men and 43 632 women who aged 19-78 years, were not currently pregnant and were without a prior diagnosis of cardiovascular disease or cancer. OUTCOME MEASURES: Gender-specific current smoking prevalence using the 1998-2017 Korea National Health and Nutrition Examination Survey. RESULTS: Our results showed gender-specific age and birth cohort effects. More specifically, the smoking prevalence peaked at their mid-20s (prevalence rate ratio (PRR): 1.54, 95% CI: 1.49 to 1.59) and cohort born in 1959-1963 (PRR: 1.63, 95% CI: 1.57 to 1.70) and then decreased in men. On the other hand, in women, the smoking prevalence consistently increased until their mid-40s (PRR: 1.53, 95% CI: 1.27 to 1.84) and in recent birth cohort groups (PRR in 1994-1998 cohort: 1.55, 95% CI: 1.13 to 2.13). The period effects declined from 1998-2002 to 2003-2007, following increasing fluctuations in both genders. The smoking-DPSEEA framework showed the absence of policy actions to target female smokers and emphasised a proactive approach that tackles the upstream causes for smoking in women. CONCLUSIONS: Men and women are clearly in different phases of the smoking epidemic in Korean population, and gender-tailored policies should be implemented.

Adiposity and mortality in Korean adults: a population-based prospective cohort study.

BACKGROUND: The Asia-Pacific obesity classification recommends using lower BMI cutoffs in Asians compared with those in Western populations. However, the supporting evidence is scarce and little is known about the exact shape of the relations between adiposity and mortality in Asians. OBJECTIVES: We investigated the relations of BMI (in kg/m2), waist circumference, and predicted body fat mass with mortality using a population-based prospective cohort of Korean men and women. METHODS: This analysis included 44,060 Korea National Health and Nutrition Examination Survey 2007-2014 participants who agreed to mortality follow-up through 31 December, 2016. At baseline, height, weight, and waist circumference were measured. Using DXA data, we derived predicted body fat and fat-free mass. Cox proportional hazards models were used to estimate HRs and 95% CIs for the associations with mortality, adjusting for potential confounders. We tested for nonlinearity using the likelihood ratio test comparing nonlinear restricted cubic spline models with linear models. RESULTS: During ≤9.5 y of follow-up, 1682 deaths were identified. The relations of BMI with all-cause and cardiovascular mortality were J-shaped with the nadir at BMI = 25.0-29.9 (P-nonlinearity < 0.001). Among participants without a history of cancer or cardiovascular disease, waist circumference (≥95 compared with 75.0-79.9 cm: HR: 2.10; 95% CI: 1.54, 2.86) and predicted body fat mass (highest compared with lowest sextiles: 2.55; 95% CI: 1.60, 4.06) were positively associated with all-cause mortality (all P-nonlinearity ≤ 0.03), as well as cancer and cardiovascular mortality. The highest mortality was observed among participants who had both high predicted fat mass and low fat-free mass. CONCLUSIONS: Our data suggest a strong positive association between adiposity and mortality in a population without pre-existing disease. We observed the lowest mortality at BMI = 25.0-29.9, suggesting that the current cutoff for overweight (BMI ≥23) may require re-evaluation and that BMI alone may not be a useful measure for indicating adiposity in Asians.

Impact of dietary risk factors on cardiometabolic and cancer mortality burden among Korean adults: results from nationally representative repeated cross-sectional surveys 1998-2016.

BACKGROUND/OBJECTIVES: Dietary factors are important contributors to cardiometabolic and cancer mortality. We examined the secular trends of nine dietary factors (fruits, vegetables, whole grains, nuts and seeds, milk, red meat, processed meat, sugar-sweetened beverages, and calcium) and the associated burdens of cardiometabolic and cancer mortality in Korea using representative cross-sectional survey data from 1998 to 2016. SUBJECTS/METHODS: Using dietary data from Korean adults aged ≥ 25 years in the Korea National Health and Nutrition Examination Survey (KNHANES), we characterized secular trends in intake levels. We performed comparative risk assessment to estimate the population attributable fraction and the number of cardiometabolic and cancer deaths attributable to each dietary factor. RESULTS: A total of 231,148 cardiometabolic and cancer deaths were attributable to nine dietary risk factors in Korea from 1998 to 2016. Suboptimal intakes of fruits and whole grains were the leading contributors. Although the intakes of fruits, vegetables, and whole grains moderately improved over time, the intake levels in 2016 (192.1 g/d, 225.6 g/d, and 10.9 g/d, respectively) remained far below the optimal levels. Deaths attributable to the low intakes of nuts and seeds (4.5 g/d), calcium (440.5 mg/d), and milk (37.1 g/d) and the high intakes of red meat (54.7 g/d), processed meat (4.7 g/d), and sugar-sweetened beverages (33.0 g/d) increased since 1998. Compared with older age groups (≥ 45 years), more unfavorable changes in dietary patterns were observed in the younger population aged 25-44 years, including more sharply increased intakes of processed meat. CONCLUSIONS: We observed improvement in the intakes of fruits, vegetables, and whole grains and unfavorable changes in the intakes of processed meat and sugar-sweetened beverages over the past few decades. Our data suggest that to reduce the chronic disease burden in Korea, more effective nutritional policies and interventions are needed to target these dietary risk factors.

Association between dietary sodium intake and disease burden and mortality in Koreans between 1998 and 2016: The Korea National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVES: Sodium intake is positively associated with blood pressure, which may increase the risk for cardiovascular disease (CVD). Therefore, we assessed the disease burden of CVD attributable to sodium intakes above 2,000 mg/day and prospectively investigated the association between dietary/urinary sodium levels and the risk of all-cause and CVD-mortality using the Korea National Health and Nutrition Examination Survey (KNHNES). SUBJECTS/METHODS: A total of 68,578 and 33,113 participants were included for comparative risk assessment (CRA) analysis and mortality analysis, respectively, and mean follow-up time for mortality was 5.4 years. CRA analysis was used to quantify attributable incidences of stroke, ischemic heart disease (IHD), and deaths attributable to sodium intake between 1998 and 2016. Cox proportional hazard regression model was used to determine the association between sodium intake and all-cause and CVD-mortality. RESULTS: Mean dietary sodium intake decreased over time, reaching 3,647 mg/day in 2016. Similarly, the population attributable fractions of stroke and IHD, and the number of CVD-associated deaths attributable to high sodium intake/excretion also decreased. In terms of association with mortality, when participants were grouped into quartiles (Q) by energy-adjusted sodium intake, those in Q2 had a lower risk of all-cause mortality than those in Q1 with lower intakes. The risk of CVD-associated mortality was higher only in females with high sodium intake in Q4 than those in Q1. CONCLUSIONS: This nationwide data indicates that, in line with previous studies of multiple cohorts, both low and high sodium intakes may be associated with an increased risk of mortality; therefore, the optimal sodium intake for Koreans needs to be revised.

The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans.

The role of angiopoietin-like 3 (ANGPTL3) in blood lipid levels, cardiovascular disease risk, and glucose metabolism has received wide attention. This study aimed to examine whether rs11207997 in ANGPTL3 is associated with a 10-year risk of diabetes mellitus (DM) and if the association is modified by the consumption of certain food groups or nutrients. A prospective cohort study was designed using the Ansan-Ansung data of the Korean Genome and Epidemiology Study (n = 7,358; age ≥40 years at baseline). Participants with the T allele of rs11207997, particularly TT homozygotes, had lower triglyceride (TG) and total cholesterol levels than those with CC. There was no association with fasting blood glucose or other biochemical parameters. ANGPTL3 mRNA was positively associated with circulating TG levels and blood pressure (all p < 0.05). Cox proportional hazard models showed that the rs11207997 T allele is associated with a lower risk of DM after adjusting for covariates (hazard ratio: 0.90, 95% confidence interval: 0.812-0.998, p = 0.046). Furthermore, the association between rs11207997 and the risk of DM was modified by dietary factors. These associations were no longer statistically significant when additionally adjusted for baseline TG, a potential mediator. Our data suggest that genetic variation of rs11207997 in the ANGPTL3 gene is associated with risk of DM, possibly through contributing to a lifelong set point of TG.

Effects of 12-week combined exercise program on self-efficacy, physical activity level, and health related physical fitness of adults with intellectual disability.

The current study examined the effects of an exercise program on health related physical fitness, self-efficacy, and physical activity levels in adults with intellectual disability. The study used pre- and posttest experimental research design with a control group. Total of 23 adults with intellectual disability were recruited with 12 assigned for the exercise group and 11 for the control group, separately. The measures of health related physical fitness included cardio pulmonary endurance (step-test), body composition (bioelectrical impedance analysis), flexibility (sit and reach), muscle endurance (sit-up), and strength (hand grip strength). Self-efficacy was measured using the physical self-efficacy scale. Accelerometers were used to measure physical activity levels. All variables were measured and evaluated twice at baseline and at the end of the program. The exercise program consisted of band exercises and rhythmic activity for 90 min, twice per week for 12 weeks. After the intervention, significant improvements were found in the experimental group in muscle endurance, self-efficacy, and physical activity levels. An exercise program may be recommended as a nonpharmaceutical method to improve the health of adults with intellectual disabilities.

Effects of virtual reality exercise for Korean adults with schizophrenia in a closed ward.

The purpose of this study was to examine the effects of virtual reality exercise (VRE) using Nintendo Wii-Fit on physical fitness of Korean adults with schizophrenia living in a mental health facility located in South Korea. Two male participants diagnosed with schizophrenia, ages 53 and 61, were recruited and selected for inclusion in this study. The intervention using the Nintendo Wii-Fit consisted of 35-min sessions, 3 times per week for 8 weeks and was facilitated by the primary researcher and two graduate students. The senior fitness test and 10-m walking test were used to measure the physical functioning, specifically, physical fitness and mobility, of the participants. The study was divided into three phases using an A-B-A single-subject design and involved multiple repeated measures of functional physical fitness. Both participants were evaluated each week for the duration of 18 weeks. Both participants exhibited measureable improvement in some of the physical fitness measures, but not in the mobility. These results thus provide preliminary evidence to support the use of VRE to improve physical function for Korean adults with schizophrenia as an alternative exercise regimen to the conventional exercise.

Genetic Association between Serum 25-Hydroxyvitamin D Levels and Lung Function in Korean Men and Women: Data from KNHANES 2011⁻2012.

The association between single-nucleotide polymorphisms (SNPs) in the vitamin D metabolic pathway and lung function is unknown. We examined the association between five SNPs on DHCR7, GC, CYP2R1, and CYP24A1 along with serum 25-hydroxyvitamin D (25(OH)D) levels and lung function in older Korean men (n = 758) and women (n = 837). Lung function was determined by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) from the data in the Korea Nutrition and Health Examination Survey 2011⁻2012. Genetic risk score (GRS) was calculated by the number of 25(OH)D-decreasing alleles of the five SNPs. Our results showed that increases in GRS were associated with reduced 25(OH)D levels (p < 0.05 for both sexes). In the entire population, FVC and FEV1 were associated with both GRS and 25(OH)D levels. In women, FVC and FEV1 were negatively associated with GRS (ß-coefficient (95% CI): -0.022 (-0.039, -0.005) and -0.020 (-0.035, -0.005), respectively; both p < 0.05), but not with 25(OH)D. However, in men, FVC and FEV1 were positively associated with 25(OH)D (ß-coefficient (95% CI): 0.008 (0.001, 0.016) and 0.008 (0.002, 0.015), respectively; both p < 0.05), but not with GRS. In conclusion, lung function was associated with genetic variation in Korean women and with 25(OH)D in Korean men.

Association between Genetic Variant of Apolipoprotein C3 and Incident Hypertension Stratified by Obesity and Physical Activity in Korea.

Apolipoprotein C3 (APOC3) is an important regulator of lipoprotein metabolism, and has been shown to be strongly associated with hypertriglyceridemia. We tested whether triglyceride-influencing genetic variants at APOC3 (T-455C, C-482T, C1100T, and SstI) are associated with the onset of hypertension (HTN) among Korean adults stratified by lifestyle-related factors in the Ansung⁻Ansan cohort within the Korean Genome and Epidemiology Study. After excluding participants with preexisting cancer, cardiovascular diseases, diabetes, and HTN, a total of 5239 men and women were included at baseline (2001⁻2002), and followed up for a median of 9.8 years. Carriers of the C allele of C1100T with body mass index <25 kg/m² showed a significantly lower HTN risk (hazard ratio (HR) than non-carriers: 0.87, 95% confidence interval (CI): 0.77⁻0.98) after adjusting for covariates. In addition, carriers of the C allele of T-455C and the T allele of C-482T with low physical activity had lower incident HTN than non-carriers (HR: 1.14, 95% CI: 1.03⁻1.26; HR: 1.13, 95% CI: 1.02⁻1.25). Our results suggest that genotype effects in APOC3 on HTN risk have been shown in lean carriers of the C allele of C1100T and in less active people having the C allele of T-455C and T allele of C-482T in a large sample of the Korean population.

Glycated Hemoglobin and Cancer Risk in Korean Adults: Results from Korean Genome and Epidemiology Study.

The purpose of this study was to test whether elevated glycated hemoglobin A1c (HbA1c) levels are associated with cancer incidence in the Korean population. In cohorts of the Korea Genome and Epidemiology Study (KoGES) consortium, we tested whether plasma levels of HbA1c were associated with all-site cancer incidence in 7,822 participants without any known history of cancer or diabetes. Cancer developed in 117 participants during the follow-up period. Subjects were subdivided into 3 categories according observed levels of HbA1c (< 5.7%, low; ≥ 5.7% and < 6.5%, mid; and ≥ 6.5%, high). The adjusted hazard ratio for all-site cancer was 3.03 (95% confidence intervals, 1.54-5.96) for the high HbA1c group relative to the low HbA1c group after adjusting for covariates. Higher circulating HbA1c levels were associated with an increased risk of all-site cancer in Korean population.

Apolipoprotein A5 3'-UTR variants and cardiometabolic traits in Koreans: results from the Korean genome and epidemiology study and the Korea National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVES: This study aimed to test the association between APOA5 3'-UTR variants (rs662799) and cardiometabolic traits in Koreans. SUBJECTS/METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained. APOA5 mRNA expression was also measured. RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports. In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes. Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [ß = -2.048, P < 0.001; ß = -2.199, P < 0.001] as well as elevation of circulating triglyceride levels [ß = 0.053, P < 0.001; ß = 0.066, P < 0.001] in both the KoGES-ASAS and KNHANES groups. In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = -0.277, P = 0.027) and circulating triglyceride level (r = -0.340, P = 0.006) but not significantly correlated with circulating HDL cholesterol level. On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms. CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES. The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.

Serum metabolite profile associated with incident type 2 diabetes in Koreans: findings from the Korean Genome and Epidemiology Study.

The identification of metabolic alterations in type 2 diabetes (T2D) is useful for elucidating the pathophysiology of the disease and in classifying high-risk individuals. In this study, we prospectively examined the associations between serum metabolites and T2D risk in a Korean community-based cohort (the Ansan-Ansung cohort). Data were obtained from 1,939 participants with available metabolic profiles and without diabetes, cardiovascular disease, or cancer at baseline. The acylcarnitine, amino acid, amine, and phospholipid levels in fasting serum samples were analyzed by targeted metabolomics. During the 8-year follow-up period, we identified 282 cases of incident T2D. Of all metabolites measured, 22 were significantly associated with T2D risk. Specifically, serum levels of alanine, arginine, isoleucine, proline, tyrosine, valine, hexose and five phosphatidylcholine diacyls were positively associated with T2D risk, whereas lyso-phosphatidylcholine acyl C17:0 and C18:2 and other glycerophospholipids were negatively associated with T2D risk. The associated metabolites were further correlated with T2D-relevant risk factors such as insulin resistance and triglyceride indices. In addition, a healthier diet (as measured by the modified recommended food score) was independently associated with T2D risk. Alterations of metabolites such as amino acids and choline-containing phospholipids appear to be associated with T2D risk in Korean adults.

Alterations in Circulating Amino Acid Metabolite Ratio Associated with Arginase Activity Are Potential Indicators of Metabolic Syndrome: The Korean Genome and Epidemiology Study.

Upregulated arginase activity, which competes with nitric oxide synthase (NOS), impairs nitric oxide production and has been implicated in various metabolic disorders. This study examined whether circulating amino acid metabolite ratios are associated with arginase and NOS activities and whether arginine bioavailability is associated with metabolic syndrome (MetS). Data related to arginase and NOS activities were collected from non-diabetic Koreans without cardiovascular disease (n = 1998) in the Ansan-Ansung cohorts (2005-2006). Subsequently, correlation and multivariate logistic regression analyses were performed. With the increase in the number of MetS risk factors, ratios of circulating amino acid metabolites, such as those of ornithine/citrulline, proline/citrulline, and ornithine/arginine, also significantly increased, whereas arginine bioavailability significantly decreased. These metabolite ratios and arginase bioavailability were also significantly correlated with MetS risk-related parameters, which remained significant after adjusting for covariates. In addition, logistic regression analysis revealed that high ratios of circulating metabolites and low arginine bioavailability, which indicated increased arginase activity, were significantly associated with a high MetS risk. This study demonstrated that altered ratios of circulating amino acid metabolites indicates increased arginase activity and decreased arginine bioavailability, both of which can be potential markers for MetS risk.