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 Table of Contents  
Year : 2019  |  Volume : 4  |  Issue : 4  |  Page : 95-98

Correlation between serum apolipoprotein A1 and serum uric acid level in patients with hyperuricemia

Center for Endocrine Metabolism and Immune Diseases, Luhe Hospital Capital Medical University, Beijing, China

Date of Submission05-Jun-2019
Date of Decision22-Nov-2019
Date of Acceptance05-Dec-2019
Date of Web Publication31-Dec-2019

Correspondence Address:
Prof. Baoyu Zhang
Department of Endocrinology, Beijing Luhe Hospital, Capital Medical University, Beijing
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ed.ed_22_19

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Objective: Patients with hyperuricemia is often associated with hyperlipidemia. Therefore, the relationship between serum apolipoprotein A1 (Apo-A1) and serum uric acid (UA) level was studied.
Methods: Seventy-three patients with gout, 43 patients with hyperuricemia, and 70 healthy controls were enrolled in the study. The liver and kidney function, blood glucose, blood lipid and other biochemical indicators were detected, and Apo-A1 content was detected by enzyme-linked immunosorbent assay.
Results: 73 patients with gout, 43 patients with hyperuricemia, and 70 healthy controls were included in the study. None of the patients had diabetes, hypertension, coronary heart disease, or other chronic diseases. There was no difference in blood lipids among the three groups. The lower expressed Apo-A1 was validated in the hyperuricemia group and gout group (P < 0.001). Among all patients, Apo-A1 levels were negatively correlated with plasma UA level (R2 = −0.4925, P < 0.0001).
Conclusion: It was confirmed that Apo-A1 was related to the change of plasma UA level to some extent.

Keywords: Gouty arthritis, hyperuricemia, serum apolipoprotein A1

How to cite this article:
Wang Y, Wang Z, Li X, Zhang B. Correlation between serum apolipoprotein A1 and serum uric acid level in patients with hyperuricemia. Environ Dis 2019;4:95-8

How to cite this URL:
Wang Y, Wang Z, Li X, Zhang B. Correlation between serum apolipoprotein A1 and serum uric acid level in patients with hyperuricemia. Environ Dis [serial online] 2019 [cited 2023 Mar 30];4:95-8. Available from: http://www.environmentmed.org/text.asp?2019/4/4/95/274520

  Introduction Top

Gouty arthritis is a heterogeneous group of disorders of purine metabolism and/or uric acid (UA) excretion. Hyperuricemia (400 μmol/L at 37°C, i.e., 6.8 mg/dl) is the most important biochemical basis of gout. However, not all patients with hyperuricemia will eventually develop gout, and there is no absolute relationship between blood UA level and gout.[1] Factors that have contributed to the development of hyperuricemia in recent years have become a research hot spot. It is well known that gout patients are often accompanied by hyperlipidemia. Apolipoprotein A1 (Apo-A1), which is mainly synthesized by hepatocytes and intestinal cells, is a major component of high-density lipoprotein (HDL).[2] HDL endows Apo-A1 with more pleiotropic anti-atherosclerosis effects, and the second major feature is HDL's anti-inflammatory properties.[3] However, there are few reports on the relationship between serum Apo-A1 levels and blood UA levels in gout patients. In this study, we measured the correlation between Apo-A1 level and serum UA in hyperuricemia patients to better understand the relationship between lipid metabolism and urea metabolism.

  Methods Top


All patients were admitted to the Department of Rheumatology and Immunology, Beijing Luhe Hospital, Capital Medical University from November 2018 to January 2019, Beijing, China. There were three groups in our study, such as 73 patients with gout, 43 patients with hyperuricemia, and 70 healthy controls who according to the blood lipid match of gout group. To exclude the effects of blood lipids, there was no difference in blood lipid between the three groups. To exclude the effects of estrogen levels, all the patients were male. All patients with gout met the diagnostic criteria for gouty arthritis jointly issued by ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) in 2015. All patients were excluded diabetes, coronary atherosclerotic heart disease, hypertension, abnormal liver function, renal insufficiency, thyroid disease, and other chronic diseases. All patients were excluded from infectious agents such as bacteria, fungi, and viruses.


All patients took 5 ml of venous blood in the fasting state. The blood samples were separated in 2 h using a high-speed refrigerated centrifuge (Thermo Fisher 2014 No. 1412022) and biochemical tests (blood glucose, blood lipid, UA, liver, and kidney functions) were performed. Serum Apo-A1 content was performed by Apo-A1 human enzyme-linked immunosorbent assay Kit (Shanghai Enzyme-linked Biotechnology Co., Ltd., Shanghai, China.).


The clinical characteristics of the study groups were tested using a general linear model for unbalanced data with Bonferroni's multiple comparison tests. The relationship between plasma UA and Apo-A1 was analyzed by Pearson's correlation. Differences in hepatic Apo-A1 secretion among untreated and treated samples in cell models were analyzed by the Kruskal–Wallis test with Dunn's multiple comparisons. The P value for linear trend was calculated using a simple regression model. The healthy controls were matched according to the blood lipids of gout patients using R software 3.5.1 (https://www.r-project.org/).

  Results Top

Basic situation

A total of 186 patients were included in this study, including 73 in the gout group, 43 in the hyperuricemia group, and 70 in the healthy control group. All the patients in the three groups were male, with no abnormal gender. In age, the hyperuricemia group and gout group were lower than the healthy control group, and there was a statistically significant difference (P < 0.05). Body mass index (BMI) of gout group was higher than that of hyperuricemia group and healthy control group, and the difference was statistically significant (P < 0.05). Blood pressure, serum creatinine, and blood glucose levels in the three groups were all within the normal range. The levels of systolic blood pressure, diastolic blood pressure, creatinine, and blood glucose in the gout group were higher than those in the control group, with statistical differences (P < 0.05). The levels of diastolic blood pressure in the hyperuricemia group were higher than that in the control group, with statistical differences (P < 0.05). The blood UA of the hyperuricemia group and the gout group was higher than that of the healthy control group, with statistical differences (P < 0.05). There was no difference in blood lipid [Table 1].
Table 1: Clinical characteristics of the hospital-based study population

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Apolipoprotein A1 level

The lower expressed Apo-A1 was validated in hyperuricemia group and gout group. The levels of Apo-A1 gradually increased in hyperuricemia, gout, and healthy controls [Figure 1]a and [Figure 1]b.
Figure 1: (a) Th lower expressed apolipoprotein A1 was validated in hyperuricemia group and gout group. (b) The levels of apolipoprotein A1 gradually increased in hyperuricemia, gout, and healthy controls

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Plasma Apo-A1 was negatively correlated with plasma UA: Plasma Apo-A1 level 21.61 ± 13.04 vg/ml was negatively correlated with plasma UA level 438.83 ± 109.31 μmol/L (R2= −0.4925, P < 0.0001) [Figure 2].
Figure 2: Plasma apolipoprotein A1 was negatively correlated with plasma uric acid

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Through multivariate linear analysis, the association of Apo-A1 with UA was established. through multiple linear analysis of age, BMI, blood pressure and biochemical indicators (serum creatinine, blood glucose, blood lipids, etc.), and plasma UA levels, UA was independently related to plasma Apo-A1 (β = −2.29, odds ratio = −3.96, P = 0.0001) [Table 2].
Table 2: Multiple linear dependence of uric acid

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  Discussion Top

Given the rise sharply over the past two decades gout prevalence, acute gouty arthritis is a major and growing public health problem.[4] Hyperuricemia is a common feature of the occurrence and the development of gout arthritis. Dyslipidemia is common in gout patients, and this study confirmed that Apo-A1 was negatively correlated with plasma UA level. In this study, the blood lipid of the gout group was matched with that of the control group. In other words, the hyperuricemia group, the gout group, and the control group were showed no significant difference in blood lipid. We confirmed that the Apo-A1 level of the hyperuricemia group (with gout attack and without gout attack) was significantly reduced. The level of Apo-A1 was negatively correlated with the plasma UA level.

Apo-A1 was negatively correlated with plasma UA levels, which was consistent with the recent article.[5] Another recent study suggested that plasma Apo-A1 in people with hyperuricemia (with gout attack and without gout attack) was no difference from the control group.[6] Conclusion was different from our study. The reasons for my analysis were as follows: there was a significant difference in plasma lipids between the hyperuricemia group and healthy control group in this study. That was, hyperuricemia group was hyperlipidemia group, whereas healthy control group was hyperlipidemia group. However, the plasma lipid of the selected population in our study was matched, which may lead to different conclusions.

HDL, which transports cholesterol in reverse through the walls of blood vessels, lowers cholesterol levels and has anti-inflammatory and antithrombotic properties.[7] Apo-A1 is the main apolipoprotein component of HDL and has the main function of reversing cholesterol transport. In addition, Apo-A1 is immunogenic. Some studies have suggested that Apo-A1 autoimmunity may affect HDL level and function.[8] In our study, Apo-A1 showed an inverse relationship with blood UA level. It may indicate that lipid metabolism and UA metabolism are crossed to some extent. The intersection of these two metabolisms may explain why gout patients are more likely to be obese or why lipid-lowering drugs have a synergistic effect on UA.

Our study is a bit thin, only confirming the correlation between Apo-A1 and UA level. In a recent study, it was suggested that gout patients had elevated levels of Apo-A1 in the acute phase of arthritis.[6] We believe that increased Apo-A1 levels during acute gouty arthritis may be associated with spontaneous regression, and a clinical process involving a “shutdown” mechanism involving self-healing or spontaneous regression to affect acute gout flares has been proposed.[9] Serum UA stimulates the secretion of Apo-A1 mRNA in a dose-dependent manner in normal human liver cells. However, chronic hyperuricemia induces excessive deposition of high dose monosodium urate crystals (MSU crystals). It causes the liver to run out of Apo-A1, which can lead to a decrease in Apo-A1 levels. On the other hand, Apo-A1 may affect the inflammatory cells and inflammatory factors to some extent, thus, Apo-A1 playing an anti-inflammatory role. Apo-A1 inhibits the activation of CD11b through the atp-binding transporter A-I transporter pathway and penetrates into the inflammatory site to play an anti-inflammatory role on human monocytes.[10] During the development of gout, the expression of interleukin (IL)-1β (a key pro-inflammatory cytokine in the pathogenesis of gout) was decreased in the presence of Apo-A1.[11],[12],[13] Although the exact mechanism of action has not been fully elucidated, Apo-A1 may affect cell interactions.[14] Apo-A1 has also been observed to inhibit lymphocyte migration by reducing adhesion expression, thereby acting as an antiinflammatory. In addition, Apo-A1 prevented t-cell-stimulated monocytes from releasing IL-1β in vitro. However, the role of Apo-A1 in regulating cell-cell contact inhibition is still unknown.[15] The phenomenon that Apo-A1 decreases with the increase of serum UA, whether it was related to the formation of MSU crystals, needs further study.

  Conclusion Top

Apo-A1 may participate in the occurrence and development of hyperuricemia through multiple factors. The specific mechanism needs further study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Yi Zheng. Gout[m]//Medicine. 3rd ed. Beijing: People's Medical Publishing House; 2017. p1227-31.  Back to cited text no. 1
Li WH, Tanimura M, Luo CC, Datta S, Chan L. The apolipoprotein multigene family: Biosynthesis, structure, structure-function relationships, and evolution. J Lipid Res 1988;29:245-71.  Back to cited text no. 2
Healy SJ, Osei K, Gaillard T. Comparative study of glucose homeostasis, lipids and lipoproteins, HDL functionality, and cardiometabolic parameters in modestly severely obese African Americans and white Americans with prediabetes: Implications for the metabolic paradoxes. Diabetes Care 2015;38:228-35.  Back to cited text no. 3
Terkeltaub R. What makes gouty inflammation so variable? BMC Med 2017;15:158.  Back to cited text no. 4
Huang H, Yu B, Liu W, Lin Q, Chen L, Chen J, et al. Serum apoprotein A1 levels are inversely associated with disease activity in gout: From a Southern Chinese Han population. Medicine (Baltimore) 2017;96:e6780.  Back to cited text no. 5
Chiang SL, Ou TT, Wu YJ, Tu HP, Lu CY, Huang CM, et al. Increased level of MSU crystal-bound protein apolipoprotein A-I in acute gouty arthritis. Scand J Rheumatol 2014;43:498-502.  Back to cited text no. 6
Lagerstedt JO, Dalla-Riva J, Marinkovic G, Del Giudice R, Engelbertsen D, Burlin J, et al. Anti-ApoA-I IgG antibodies are not associated with carotid artery disease progression and first-time cardiovascular events in middle-aged individuals. J Intern Med 2019;285:49-58.  Back to cited text no. 7
Croca S, Bassett P, Chambers S, Davari M, Alber KF, Leach O, et al. IgG anti-apolipoprotein A-1 antibodies in patients with systemic lupus erythematosus are associated with disease activity and corticosteroid therapy: An observational study. Arthritis Res Ther 2015;17:26.  Back to cited text no. 8
Ortiz-Bravo E, Sieck MS, Schumacher HR Jr. Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. Immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model. Arthritis Rheum 1993;36:1274-85.  Back to cited text no. 9
Thacker SG, Zarzour A, Chen Y, Alcicek MS, Freeman LA, Sviridov DO, et al. High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation. Immunology 2016;149:306-19.  Back to cited text no. 10
Martinon F, Burns K, Tschopp J. The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002;10:417-26.  Back to cited text no. 11
Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006;440:237-41.  Back to cited text no. 12
Martinon F, Mayor A, Tschopp J. The inflammasomes: Guardians of the body. Annu Rev Immunol 2009;27:229-65.  Back to cited text no. 13
Hyka N, Dayer JM, Modoux C, Kohno T, Edwards CK 3rd, Roux-Lombard P, et al. Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes. Blood 2001;97:2381-9.  Back to cited text no. 14
Burger D, Dayer JM. Cytokines, acute-phase proteins, and hormones: IL-1 and TNF-alpha production in contact-mediated activation of monocytes by T lymphocytes. Ann N Y Acad Sci 2002;966:464-73.  Back to cited text no. 15


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]

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