Association of plasma free amino acids with hyperuricemia in relation to diabetes mellitus, dyslipidemia, hypertension and metabolic syndrome

Abstract

Previous studies demonstrated independent contributions of plasma free amino acids (PFAAs) and high uric acid (UA) concentrations to increased risks of lifestyle-related diseases (LSRDs), but the important associations between these factors and LSRDs remain unknown. We quantified PFAAs and UA amongst Japanese subjects without LSRDs (no-LSRD, n = 2805), and with diabetes mellitus (DM, n = 415), dyslipidemia (n = 3207), hypertension (n = 2736) and metabolic syndrome (MetS, n = 717). The concentrations of most amino acids differed significantly between the subjects with and without hyperuricemia (HU) and also between the no-LSRD and LSRD groups (p < 0.05 to 0.001). After adjustment, the logistic regression analyses revealed that lysine in DM, alanine, proline and tyrosine in dyslipidemia, histidine, lysine and ornithine in hypertension, and lysine and tyrosine in MetS demonstrated significant positive associations with HU among the patients with LSRDs only (p < 0.05 to 0.005). By contrast, arginine, asparagine and threonine showed significant inverse associations with HU in the no-LSRD group only (p < 0.05 to 0.01). For the first time, we provide evidence for distinct patterns of association between PFAAs and HU in LSRDs, and postulate the possibility of interplay between PFAAs and UA in their pathophysiology.

Associations of Amino Acid and Acylcarnitine Profiles With Incident Hyperuricemia in Middle‐Aged and Older Chinese Individuals

“…To our knowledge, this is the first population-based study to evaluate associations between multiple metabolites and longitudinal change in uric acid and incident hyperuricemia, implying that metabolite perturbations could precede and predict the onset of hyperuricemia. All previous studies were cross-sectional in nature and focused on gout or hyperuricemia per se rather than on changes in uric acid, a continuous trait that can serve as an early sign of hyperuricemia risk (6,7,(24)(25)(26). In some earlier studies, investigators focused primarily on associations with amino acids, including glutamine, glycine, aspartic acid, and serine, which are known to contribute to the biosynthesis of purine (25,26).…”

“…Metabolites such as amino acids are known to be involved in uric acid synthesis, excretion, and regulation (5). To date, only a few cross-sectional studies have shown correlations between metabolites (mainly amino acids) and hyperuricemia or uric acid levels (6,7). Metabolomics signatures in the pathogenesis of hyperuricemia and even gout risk have not been studied in a longitudinal setting.…”

Modulation of Free Amino Acid Profile in Healthy Humans Administered with Mastiha Terpenes. An Open-Label Trial

“…This relationship is supported by a recent study in Japanese subjects with or without lifestyle-risk factors for future cardiovascular disease exploring the association between plasma-free AAs and high levels of UA. Apart from significant correlations of plasma-free AAs with UA, significant inverse associations with high UA levels were observed for arginine, asparagine and threonine in healthy subjects as well, indicating the possibility of interplay between plasma-free AAs and UA [ 21 ]. However, hereby, whether the changes in AAs have a direct relationship with antioxidant status or whether the relationship between plasma-free AAs and UA is causal remain unanswered.…”

Relationship of reduced glomerular filtration rate with alterations in plasma free amino acids and uric acid evaluated in healthy control and hypertensive subjects

“…Conversely, the kidneys play major roles in the regulation of circulating UA level as they reabsorb around 90% of filtered urate and eliminate approximately 60–70% of the total UA produced in the human body 12 . On the other hand, we recently showed a clear relationship of HU with hypertension 7 ; and the role of HU might be causal in the development of hypertension 13 .…”

“…Published data suggest that in chronic kidney diseases, alterations in the levels of plasma free amino acids (PFAAs) appear early and are more pronounced in advanced stages of it 6 . Also, published research works suggest the possibility of the changes in amino acid metabolism in the pathogenesis of hypertension 7,8 . Existing evidence also indicate a clear relationship of an elevated level of circulating uric acid (UA), known as hyperuricemia (HU) with the accelerated decline in kidney function 9,10 .…”