Genetic Variants Linked to Myocardial Infarction in Individuals with Non-Alcoholic Fatty Liver Disease and Their Potential Interaction with Dietary Patterns.

In recent studies, non-alcoholic fatty liver disease (NAFLD) has been associated with a high risk of ischemic heart disease. This study aimed to investigate a genetic variant within a specific gene associated with myocardial infarction (MI) among patients with NAFLD. We included 57,205 participants from a Korean genome and epidemiology study. The baseline population consisted of 45,400 individuals, with 11,805 identified as patients with NAFLD. Genome-wide association studies were conducted for three groups: the entire sample, the healthy population, and patients with NAFLD. We defined the p-value < 1 × 10-5 as the nominal significance and the p-value < 5 × 10-2 as statistically significant for the gene-by-nutrient interaction. Among the significant single-nucleotide polymorphisms (SNPs), the lead SNP of each locus was further analyzed. In this cross-sectional study, a total of 1529 participants (2.8%) had experienced MI. Multivariable logistic regression was performed to evaluate the association of 102 SNPs across nine loci. Nine SNPs (rs11891202, rs2278549, rs13146480, rs17293047, rs184257317, rs183081683, rs1887427, rs146939423, and rs76662689) demonstrated an association with MI in the group with NAFLD Notably, the MI-associated SNP, rs134146480, located within the SORCS2 gene, known for its role in secreting insulin in islet cells, showed the most significant association with MI (p-value = 2.55 × 10-7). Our study identifies candidate genetic polymorphisms associated with NAFLD-related MI. These findings may serve as valuable indicators for estimating MI risk and for conducting future investigations into the underlying mechanisms of NAFLD-related MI.

Relationship between Handgrip Strength and Incident Diabetes in Korean Adults According to Gender: A Population-Based Prospective Cohort Study.

(1) Background: Diabetes mellitus (DM) is a well-known disease that causes comorbidities such as chronic kidney disease (CKD) and cardiovascular disease. Therefore, it is necessary to develop diagnostic tools to prevent DM. Handgrip strength, a known diagnostic tool for sarcopenia, is a predictor of several diseases. However, the value of handgrip strength as an indicator of incident DM in Asian populations remains unknown. This study aimed to identify the relationship between handgrip strength and incidence of DM in Korean adults according to sex. (2) Methods: A total of 173,195 participants registered in a nationwide cohort were included in this study. After applying the exclusion criteria, 33,326 participants remained. DM occurred in 1473 individuals during the follow-up period (mean follow-up period, 4.1 years). To reduce the impact of body size, the study population was subdivided into quartiles of relative handgrip strength, defined as absolute handgrip strength divided by body mass index. Multivariate Cox regression analysis revealed that the relative handgrip strength was inversely associated with new-onset DM. (3) Results: Compared with the lowest quartile (Q1), the hazard ratios (HRs) [95% confidence intervals (CIs)] for new-onset DM for the highest quartiles (Q4) was 0.60 (0.43-0.84) in men and 0.72 (0.52-0.99) in women after adjusting for confounding factors. The incidence of DM decreased with the increase in the relative handgrip strength. These inverse relationships were statistically more significant in men than in women. (4) Conclusions: This novel study revealed that relative handgrip strength is related to incident DM in both men and women. Relative handgrip strength can be used as a practical tool to prevent DM. Regular measurement of handgrip strength can be used to detect DM.

Elevated Uric Acid Levels with Early Chronic Kidney Disease as an Indicator of New-Onset Ischemic Heart Disease: A Cohort of Koreans without Diabetes.

Several studies have showed that hyperuricemia is related to the development of ischemic heart disease (IHD). There is also growing evidence indicating that hyperuricemia may contribute to the progression of IHD as a pathogenic factor. Ironically, uric acid can be an antioxidant agent, as shown in experimental studies. The aim of our study is to analyse the association between uric acid and IHD with early-stage chronic kidney disease (CKD). Data were assessed from 17,492 participants without cardiovascular disease from the Korean Genome and Epidemiology Study (KoGES) and Korea Health Insurance Review and Assessment (HIRA) data. The subjects were categorized as four groups according to CKD and uric acid levels. We retrospectively evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD by using multivariate Cox regression analysis over a 4-year period from the baseline survey. During the follow-up, 335 individuals (3.4%; 236 men and 99 women) developed IHD. Compared to the participants without elevated uric acid and early CKD HRs for incident IHD according to uric acid levels and early CKD, the uric acid level was 1.13 (95% CI, 0.86-1.48) in participants with elevated uric acid and without early CKD, 0.99 (95% CI, 0.55-1.77) in participants without elevated uric acid and with early CKD, and 1.65 (95% CI, 1.03-2.66) in participants with elevated uric acid and early CKD after adjusting for confounding metabolic factors. Early CKD and high uric acid levels increased the risk of new-onset IHD (HR, 1.65; 95% CI, 1.03-2.66). Elevated uric acid levels were related to an increased risk of incident IHD in early-stage CKD patients. It is expected that uric acid can be a reliable predictor for IHD, even in early-stage CKD patients; thus, in those with CKD, proactively managing uric acid levels can play a significant role in reducing the risk of cardiovascular disease.

Association of handgrip strength with new-onset CKD in Korean adults according to gender.

Introduction: Handgrip strength (HGS) is an indicator of many diseases such as pneumonia, cardiovascular disease and cancer. HGS can also predict renal function in chronic kidney disease (CKD) patients, but the value of HGS as a predictor of new-onset CKD is unknown. Methods: 173,195 subjects were recruited from a nationwide cohort and were followed for 4.1 years. After exclusions, 35,757 participants remained in the final study, and CKD developed in 1063 individuals during the follow-up period. Lifestyle, anthropometric and laboratory data were evaluated in relation to the risk of CKD. Results: The participants were subdivided into quartiles according to relative handgrip strength (RGS). Multivariate Cox regression demonstrated that RGS was inversely associated with incident CKD. Compared with the lowest quartile, the hazard ratios (HRs) [95% confidence intervals (CIs)] for incident CKD for the highest quartile (Q4) was 0.55 (0.34-0.88) after adjusting for covariates in men and 0.51 (0.31-0.85) in women. The incidence of CKD decreased as RGS increased. These negative associations were more significant in men than in women. The receiver operating characteristic (ROC) curve showed that baseline RGS had predictive power for new-onset CKD. Area under the curve (AUC) (95% CIs) was 0.739 (0.707-0.770) in men and 0.765 (0.729-0.801) in women. Conclusion: This is the novel study demonstrating that RGS is associated with incident CKD in both men and women. The relationship between RGS and incident CKD is more significant in women than in men. RGS can be used in clinical practice to evaluate renal prognosis. Regular measurement of handgrip strength is essential to CKD detection.

The Combination of Uric Acid and Hemoglobin Levels Predicts the Incident Risk of Ischemic Heart Disease More Than Uric Acid Alone in Non-Diabetic Koreans: A Longitudinal Study Using National Health Insurance Data.

Uric acid has been related to cardiovascular disease (CVD). Recently, slightly elevated hemoglobin (Hb) was also shown to be associated with CVD. We retrospectively investigated the joint effect of uric acid and elevated Hb by comparing normal-range uric acid alone on incident ischemic heart disease (IHD) risk in a large cohort of non-diabetic Korean adults using National Health Insurance data. We assessed 16,786 participants without diabetes (8595 men and 8191 women) using extensive cohort data. High Hb was defined as ≥16.4 g/dL in men and 13.8 g/dL in women (>75th percentile). We analyzed the data using two different methods. First, the participants were divided into quartiles according to uric acid levels. Second, subjects were also divided into quartiles: reference (group 1), high uric acid and normal Hb (group 2), normal uric acid and high Hb (group 3), and normal uric acid and high Hb (group 4). We evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox regression analysis over a 50-month follow-up. During the follow-up, 345 (1.9%) participants developed IHD. In the analysis using both uric acid and Hb, compared with the reference group, the HRs for IHD were 1.37 (95% CI, 1.01-1.86) in the second group, 1.63 (95% CI, 1.21-2.21) in the third group, and 1.86 (95% CI, 1.30-2.67) in the fourth group after adjusting for IHD risk factors. Subsequently, patients with high uric acid are more likely to develop incident IHD than control patients. Moreover, we confirmed the joint effects of high uric acid and high hemoglobin on incident IHD. Awareness of these interactions is essential for clinicians. Risk factor management and screening for IHD are part of the routine management of patients with high uric acid and Hb.

Association of Handgrip Strength with Diabetes Mellitus in Korean Adults According to Sex.

Diabetes mellitus (DM) is known to lead to many diseases such as cardiovascular disease and chronic kidney diseases. Therefore, it is essential to find diagnostic tools to prevent DM. This study aimed to find the association between handgrip strength and the prevalence of diabetes mellitus (DM) in Korean adults with respect to sex and menopause. A total of 26,536 participants (12,247 men, 6977 premenopausal women, and 7312 postmenopausal women) aged >19 years were recruited. The study population was divided into quartiles of relative handgrip strength. Logistic regression was used to analyse the association between relative handgrip strength and the prevalence of DM. Compared with the lowest quartile, the odds ratio (95% confidence interval (CI)) the prevalence of DM for the fourth quartile (Q4) was 0.57 (0.43−0.75) after adjusting for confounding factors in men; 0.33 (0.14−0.75), premenopausal women; and 0.82 (0.63−1.07), postmenopausal women. The prevalence of DM decreased as relative handgrip strength increased. This inverse association was more significant in men and premenopausal women than that in postmenopausal women.

Dyslipidaemia-Genotype Interactions with Nutrient Intake and Cerebro-Cardiovascular Disease.

A comprehensive understanding of gene-diet interactions is necessary to establish proper dietary guidelines to prevent and manage cardio-cerebrovascular disease (CCD). We investigated the role of genetic variants associated with dyslipidaemia (DL) and their interactions with macro-nutrients for cardiovascular disease using a large-scale genome-wide association study of Korean adults. A total of 58,701 participants from a Korean genome and epidemiology study were included. Their dietary intake was assessed using a food frequency questionnaire. Dyslipidaemia was defined as total cholesterol (TCHL) ≥ 240 mg/dL, high-density lipoprotein (HDL) < 40 mg/dL, low-density lipoprotein (LDL) ≥ 160 mg/dL, triglycerides (TG) ≥ 200 mg/dL, or dyslipidaemia history. Their nutrient intake was classified as follows: protein intake: high ≥ 30%, 30% > moderate ≥ 20%, and 20% > low in daily total energy intake (TEI); carbohydrate intake: high ≥ 60%, 60% > moderate ≥ 50%, and 50% > low; fat intake: high ≥ 40%, 40% > moderate ≥ 30%, and 30% > low. Odds ratios and 95% confidence intervals were calculated after adjusting for age; sex; body mass index (BMI); exercise status; smoking status; alcohol intake; principal component 1 (PC1); principal component 2 (PC2); and intake of carbohydrates, fats, and proteins. This analysis included 20,596 patients with dyslipidaemia and 1027 CCD patients. We found that rs2070895 related to LIPC was associated with HDL-cholesterol. Patients with the minor allele (A) in rs2070895 had a lower risk of CCD than those carrying the reference allele (G) (odds ratio [OR] = 0.8956, p-value = 1.78 × 10−2). Furthermore, individuals consuming protein below 20% TEI with the LIPC reference allele had a higher risk of CCD than those with the minor allele (interaction p-value 6.12 × 10−3). Our findings suggest that the interactions of specific polymorphisms associated with dyslipidaemia and nutrients intake can influence CCD.

Genome-Wide Association of New-Onset Hypertension According to Renin Concentration: The Korean Genome and Epidemiology Cohort Study.

The renin-angiotensin system (RAS) is a crucial regulator of vascular resistance and blood volume in the body. This study aimed to examine the genetic predisposition of the plasma renin concentration influencing future hypertension incidence. Based on the Korean Genome and Epidemiology Cohort dataset, 5211 normotensive individuals at enrollment were observed over 12 years, categorized into the low-renin and high-renin groups. We conducted genome-wide association studies for the total, low-renin, and high-renin groups. Among the significant SNPs, the lead SNPs of each locus were focused on for further interpretation. The effect of genotypes was determined by logistic regression analysis between controls and new-onset hypertension, after adjusting for potential confounding variables. During a mean follow-up period of 7.6 years, 1704 participants (32.7%) developed hypertension. The low-renin group showed more incidence rates of new-onset hypertension (35.3%) than the high-renin group (26.5%). Among 153 SNPs in renin-related gene regions, two SNPs (rs11726091 and rs8137145) showed an association in the high-renin group, four SNPs (rs17038966, rs145286444, rs2118663, and rs12336898) in the low-renin group, and three SNPs (rs1938859, rs7968218, and rs117246401) in the total population. Most significantly, the low-renin SNP rs12336898 in the SPTAN1 gene, closely related to vascular wall remodeling, was associated with the development of hypertension (p-value = 1.3 × 10-6). We found the candidate genetic polymorphisms according to blood renin concentration. Our results might be a valuable indicator for hypertension risk prediction and preventive measure, considering renin concentration with genetic susceptibility.

Association of Muscle Strength with Non-Alcoholic Fatty Liver Disease in Korean Adults.

Sarcopenia is known to be associated with non-alcoholic fatty liver disease (NAFLD). However, few studies have revealed the association between muscle strength and prevalence of NAFLD. We investigated the association by using relative handgrip strength in a nationwide cross-sectional survey. The participants were recruited from the Korean National Health and Nutrition Examination Surveys (KNHANES). A total of 27,531 subjects from the KNHANES were selected in our study. We used normalized handgrip strength, which is called relative handgrip strength. The index was defined as handgrip strength divided by BMI. These subjects were divided into quartile groups according to relative handgrip strength. NAFLD was defined as hepatic steatosis index >36. Multinomial logistic regression was analysed to investigate the association between relative handgrip strength with prevalence of NAFLD. The mean age of study population was 45.8 ± 0.3 in men, and 48.3 ± 0.2 in women. The proportion of males was 37.5%. In multiple linear regression, relative handgrip strength was inversely associated with HSI index (Standardized ß = -0.70; standard error (SE), 0.08; p < 0.001 in men, Standardized ß = -0.94; standard error (SE), 0.07; p < 0.001 in women). According to the logistic regression model, the prevalence of NAFLD decreased with quartile 4 groups in relative handgrip strength, compared with quartile 1 groups (OR 0.42 [0.32-0.55] in men; OR 0.30 [0.22-0.40] in women). Relative handgrip strength, used as a biomarker of sarcopenia, is independently inversely associated with NAFLD.

Early Chronic Kidney Disease (G1-G3a) in Combination with Steatosis as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study in Non-Diabetic Koreans.

Hepatic steatosis and chronic kidney disease (CKD) in the advanced stages are closely related to cardiovascular diseases. Despite the potential connection between early CKD (G1-G3a) and hepatic steatosis on cardiometabolic risks, few studies have revealed their causal link to ischemic heart disease (IHD). We prospectively investigated the combined effect of CKD in earlier stages and hepatic steatosis on incident IHD risk in large-scale, non-diabetic Koreans. Data were assessed from 16,531 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. We divided the study population into four groups according to the existence of early CKD and hepatic steatosis: controls, early CKD only, hepatic steatosis only, and both early CKD and hepatic steatosis. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period. During the follow-up period, 326 (2.0%) patients developed IHD. HRs of IHD in the four groups were 1.00 (controls), 1.26 (95% CI 0.72-2.19), 1.19 (95% CI 0.90-1.57) and 1.76 (95% CI 1.04-2.97), respectively, after adjusting for potential confounding variables. Even less than stage 3A, CKD could precede and predict IHD in patients with hepatic steatosis.

C-reactive protein-to-albumin ratio and 8-year incidence of type 2 diabetes: the Korean genome and epidemiology study.

AIMS: The C-reactive protein-to-albumin ratio (CAR) has been reported as a novel prognostic marker in serious illness and various inflammatory diseases. The aim of this study is to investigate the association of CAR with incidence risk of type 2 diabetes in adults without chronic disease. METHODS: A total of 5904 participants aged 40 to 69 years were selected from the Korean Genome and Epidemiology Study who were observed over 12 years. Multivariable logistic regression was analyzed to examine the relationship between CAR tertiles and incident diabetes. The predictive power of new-onset diabetes by CAR and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured using the random forest model. RESULTS: During a mean follow-up period of 7.6 years, 701 subjects (11.9%) developed diabetes. Compared with the lowest CAR group, the highest CAR group was associated with incidence of diabetes (OR 1.60; 95% CI 1.24-1.89) after adjustment for other potential confounding factors. In the random forest model, CAR did not show a significant difference in prediction of new-onset diabetes compared with HOMA-IR (p = 0.561). CONCLUSIONS: CAR, which is a ratio of commonly used biomarkers and reflects both oxidative stress and antioxidants, is suggested as a predictor of incident diabetes.

Body fat change and 8-year incidence of hypertension: Korean Genome and Epidemiology Study.

Hypertension is strongly correlated with an increased risk of cardiovascular events. Recent studies have demonstrated that body fat percentage (BF%) is associated with cardiometabolic risk factors. The aim of this study was to investigate the association between a change in BF% and body mass index (BMI) and the incidence of new-onset hypertension in a normotensive Korean cohort. At baseline (2001-2002), 8848 participants aged 40-70 years were recruited for the study; follow-up surveys were completed in the year 2012. A total of 3902 adults (1866 men and 2036 women) were included in the final analysis. These subjects were divided into quartile groups according to changes in BF% and were followed for 8.4 years to monitor for the development of hypertension. A Poisson regression model was used to evaluate the relative risk (RR) for hypertension according to BF% change quartile. Additionally, we also stratified participants into four groups according to BMI change levels and body fat change levels. Finally, we compared two factors, BF% change, and BMI change, to determine which is more predictive of incident hypertension. In an adjusted model, compared with the lowest BF% quartile group, the risk of new-onset hypertension significantly increased with BF% change: Changes in risk were 0%-2.0% for quartile 3 subjects (RR: 1.32 [1.06-1.63]) and 2.0%-8.9% for quartile 4 participants (RR: 1.78 [1.43-2.19]). We also revealed that the RR for new-onset hypertension was 1.81 (95% CI: 1.47-2.21) for quartile 4 group subjects, compared with subjects in quartile 1 (change in BMI -6.80 to -0.86% [kg/m2 ]). Body fat gain and BMI increase were predictors of hypertension in this community-based Korean cohort.

Differences in subgingival microflora of Korean and German periodontal patients.

PURPOSE: The goal of this study was to characterize the microbiological profile in samples of subgingival plaque taken from periodontal patients with different ethnic origin. METHODS: 178 patients (n=90 from South Korea and n=88 from Germany; age: 45.4 +/- 10.4 years) were diagnosed with severe generalized periodontitis. In all patients the deepest pocket of each quadrant was sampled for subgingival plaque. The four samples per patient were pooled and subsequently analysed with a 16s-RNA-gene probe test. RESULTS: Prevalence of Aggregatibacter actinomycetemcomitans was significantly higher in German patients (47.7%) compared to Korean patients (26.7%) (p < 0.01, chi(2)-test). For Tannerella forsythia and porphyromonas gingivalis, differences between Germans and Koreans were not as pronounced. A statistically significant difference could also be found for Treponema denticola (Germans: 95.5%, Koreans: 81.1%, p < 0.01, chi(2)-test). After logarithmic transformation, bacterial counts differed for all microorganisms under investigation between Germans and Koreans, even after using a General Linear Model/Analysis of Covariance (GLM/ANCOVA) to adjust for gender, age, smoking status, pocket probing depths (PPD) of sampled teeth, and gingival bleeding index (GBI). CONCLUSION: Depending on their ethnic origin, the microbiological profile of pooled subgingival plaque sample seems to differ significantly between patients of Caucasian and Asian ethnic origin.