Lipocalin-2 Variants and Their Relationship With Cardio-Renal Risk Factors

Dahui Li; Haoyun Li; Carlie Bauer; Yue Hu; Joshua R Lewis; Aimin Xu; Itamar Levinger; Yu Wang

doi:10.3389/fendo.2021.781763

Lipocalin-2 Variants and Their Relationship With Cardio-Renal Risk Factors

Front Endocrinol (Lausanne). 2021 Dec 6:12:781763. doi: 10.3389/fendo.2021.781763. eCollection 2021.

Authors

Dahui Li^{1

2

3}, Haoyun Li^{1

2

3}, Carlie Bauer⁴, Yue Hu^{2

3}, Joshua R Lewis^{5

6

7}, Aimin Xu^{2

3}, Itamar Levinger^{4

8}, Yu Wang^{1

2}

Affiliations

¹ The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
² Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
³ Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁴ Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia.
⁵ Medical School, University of Western Australia, Perth, WA, Australia.
⁶ Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
⁷ Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
⁸ Australian Institute for Musculoskeletal Science, Victoria University, University of Melbourne, Western Health, St. Albans, VIC, Australia.

Abstract

Objectives: To investigate the serum, plasma and urine levels of lipocalin-2 (LCN2) variants in healthy humans and their associations with risk factors for cardiometabolic (CMD) and chronic kidney (CKD) diseases.

Methods: Fifty-nine males and 41 females participated in the study. Blood and urine were collected following an overnight fasting. LCN2 variants were analyzed using validated in-house ELISA kits. Heart rate, blood pressure, lipids profile, glucose, adiponectin, high-sensitivity C-reactive protein (hsCRP), creatinine, cystatin C, and biomarkers for kidney function were assessed.

Results: The levels of hLcn2, C87A and R81E in serum and urine, but not plasma, were significantly higher in men than women. Increased levels of LCN2 variants, as well as their relative ratios, in serum and plasma were positively associated with body mass index, blood pressure, triglyceride and hsCRP (P<0.05). No significant correlations were found between these measures and hLcn2, C87A or R81E in urine. However, LCN2 variants in urine, but not plasma or serum, were correlated with biomarkers of kidney function (P<0.05).

Conclusions: Both the serum and plasma levels of LCN2 variants, as well as their ratios are associated with increased cardiometabolic risk, whereas those in urine are correlated with renal dysfunction. LCN2 variants represent promising biomarkers for CMD and CKD.

Keywords: Lipocalin-2 (Lcn2); biomarker; heart; kidney; protein variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Female
Genetic Variation / genetics*
Heart Diseases / genetics*
Heart Diseases / metabolism
Humans
Kidney Diseases / genetics*
Kidney Diseases / metabolism
Lipocalin-2 / genetics*
Lipocalin-2 / metabolism
Male
Middle Aged
Risk Factors

Substances

LCN2 protein, human
Lipocalin-2