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.

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.

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.

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 (β-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 (β-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.