Evaluation Between Serum Concentrations of Lipocalin-2 and Metabolic Syndrome and its Components in Korean-Chinese and Han-Chinese Individuals from Yanbian Area

Abstract

Objectives:

To investigate the association between the blood concentration of lipocalin-2 (LCN2) in local multiethnic residents and the increased risk for the development of metabolic syndrome (MS) in the Yanbian Korean Autonomous Prefecture population.

Methods:

A total of 2078 subjects with (study group) or without (control group) MS (1217 Korean-Chinese and 861 Han-Chinese subjects) were included in this study. MS subjects were divided into five groups according to ethnicity and MS components. They were assessed for smoking history, drinking history, past medical history, general demographic characteristics, and LCN2 concentrations.

Results:

LCN2 concentrations were higher in all ethnic MS groups than in the control group, and the highest concentrations were detected in Han-Chinese subjects with dyslipidemia. Moreover, LCN2 concentrations were significantly higher in Korean-Chinese individuals with all MS components than in the control group. Logistic regression analyses were conducted. In the unadjusted models, Korean-Chinese and Han-Chinese individuals with high LCN2 concentrations both faced a risk of MS with odds ratios (ORs) of 2.339 (95% confidence interval [CI]: 1.632–3.352) and 1.523 (95% CI: 1.101–2. 108), respectively. After the adjustment, the risk only remained in Korean-Chinese individuals, with an OR of 1.818 (95% CI: 1.031–3.207).

Conclusion:

Elevated circulating LCN2 was associated with the increased incidence of MS, and the effect in Korean-Chinese individuals was stronger than that in Han-Chinese individuals.

Introduction

In recent years, the prevalence of metabolic syndrome (MS) in the global adult population has reached 20%–25%,¹ and the prevalence data vary in China for the wide diversity in sociocultural background and deferent levels of economic development, which contributed to the increasing prevalence of obesity, diabetes, and cardiovascular disease. The prevalence of MS reached 24.2% in 2012 and 33.9% in 2017.^2,3 Data from China Nutrition and Health surveillance (2015–2017) showed the prevalence of MS in the north China (35.9%) was higher than that in the south (27.4%).⁴ Data from the China Multi-Ethnic Cohort (CMEC) focused on the prevalence of different altitude in Southwest China, an area which covered a wide range of altitudes situation and ethics. The highest prevalence of MS was detected in higher altitude groups (26.70%).⁵ MS is indicated by the clustering of metabolic disorders, such as obesity, dyslipidemia, insulin resistance (IR), hypertension, and a proinflammatory state.^6

–9 Various components of MS can cause more severe damage¹⁰ and can also increase the risk and burden of cardiovascular disease.¹¹ Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin, is a 25-kDa secreted glycoprotein that belongs to the lipocalin superfamily and is dispersed among adipose tissue, liver, lung, brain tissue, and skeletal muscle.^12
–14 LCN2 has been reported to be involved in obesity, IR, and other metabolic disorders,^15,16 and studies both on humans and animal models have reported elevated concentrations of circulating LCN2 in the subjects with MS.^17,18 On the other hand, LCN2 has been shown to inhibit diet-induced obesity, maintain glucose tolerance, and prevent dyslipidemia.^19,20

China is a multiethnic country with different metabolic statuses among individuals because of its various lifestyle habits and regions. At present, there is inconsistency in the prevalence of various metabolic disorders between Korean and Han populations. Some studies have shown that the prevalence of MS and hypertension in Korean individuals is higher than that in the Han population, and it has been reported that there is a varied prevalence of MS.^21,22 However, the role of LCN2 in the MS components in different metabolic states and different populations is still controversial,^23

–26 and the interaction between them still needs to be clarified. Therefore, the current study was designed to investigate the association between LCN2 and MS in the Yanbian Korean Autonomous Prefecture population.

Materials and Methods

Participants

This was a cross-sectional study conducted among a total of 3875 participants above 20 years old with complete evaluation data of anthropometric, clinical, and biochemical status from a community in Yan Ji city, Jilin Province, China, from April to September 2017. Exclusion criteria included liver dysfunction (triple increase in aminotransferase), liver cirrhosis, malignancy, and other chronic diseases such as chronic renal disease. Then, a total of 2078 subjects (1217 Korean-Chinese and 861 Han-Chinese) were included. The match groups between MS participants as the study group and non-MS participants as the control group in different ethnic groups were performed by propensity score matching according to their age and sex. Finally, a total of 1214 participants were included, with, respectively, of 253 pairs of Korean-Chinese and 354 pairs of Han-Chinese were matched.

Questionnaire

The sociodemographic data were adopted by a unified questionnaire, and the participants were investigated by the same group of personnel after professional training. The contents of the questionnaire mainly included general demographic characteristics, smoking history (smoked at least one cigarette per week during at least 6 months, or at least 100 cigarettes in their life time, and those who had quit smoking), drinking history (alcohol consumption over 50 g per week and over 1 time per weak), disease history, etc. The investigator was responsible for measuring the waist circumference (WC), height, weight, blood pressure, and other general physical indicators of the subjects, helping them complete the questionnaire, and then uniformly entering them into the database after the survey.

Measurement of clinical parameters

After 8 hrs of fasting, 3 mL of venous blood was obtained from all participants, and then samples were centrifuged for plasma and stored at −80°C before analysis. A complete blood count and neutrophile classification were measured using an automated hematology analyzer (Mindray; Shenzhen; China). Fasting plasma glucose levels (FPG) were measured using the hexokinase method. Levels of total cholesterol (TC) (CHOD-PAP method), triglyceride (TG) (GPO-PAP method), low-density lipid cholesterol (LDL) (surfactant LDL assay), high-density lipid cholesterol (HDL) (catalase HDL assay), alanine aminotransaminase (ALT) (alanine substrate method), aspartate aminotransferase (AST) (aspartic acid substrate method), gamma-glutamyl transpeptidase (GGT) (GPNA substrate method), serum urinary acid (SUA) (uricase method), blood urea nitrogen (BUN) (urease-glutamate dehydrogenase method), creatin (CREA) (sarcosine oxidase method), total bilirubin (TBIL) (chemical oxidation method), direct bilirubin (DBIL) (chemical oxidation method), total protein (TP) (biuret method), albumin (ALB) (bromocresol green method), and albumin globulin ratio (A/G) were measured using a chemiluminescence autoanalyzer (Modular Cobas 702; Roche; Mannheim; Germany). All the assay kits were provided by Roche Company.

Measurement of LCN2

Plasma samples were stored at −80°C in a refrigerator. Enzyme-linked immunosorbent assays and inserted software for analysis were performed according to the manufacturer’s instructions (BioTek Instruments, Inc. Winooski, VT, USA) to quantify the serum concentration of LCN2. The microplate reader is the product of BioTek Company (Winooski, VT, USA).

Definition of metabolic syndrome

MS was categorized according to the Chinese Diabetes Society Chinese guidelines for the prevention and treatment of type 2 diabetes mellitus (2020 edition)²⁷ as the presence of at least three of the following abnormalities: 1) central obesity: WC ≥90 cm for males and ≥85 cm for females; 2) hyperglycemia: fasting blood glucose ≥6.1 mmol/L or 2 hr post loading glucose ≥7.80 mmol/L and/or previously diagnosed with diabetes mellitus and under treatment; 3) hypertension: blood pressure ≥130/85 mmHg and/or previously diagnosed with hypertension and under treatment; 4) fasting TG: TG≥1.70 mmol; and 5) fasting HDL-C: HDL-C ≤1.04 mmol/L.

Statistics

All the values reported are expressed as the mean ± SD or median and interquartile range using Windows SPSS/PC (version 26.0; SPSS; Chicago, IL, USA). After log-transforming nonnormally distributed variables such as TG, AST, ALT, GGT, TBIL, DBIL, and LCN2, they turned into normally distributed. Differences between groups were calculated using Student’s t test for continues variables with normal distribution and chi-square tests for categorical variables. The strength of the association between variables was calculated using Spearman’s method for nonparametric variables. Logistic regression analysis using the existence of LCN2 as a dependent variable was conducted to determine the relative contributions. P values < 0.05 indicated statistical significance.

Results

Comparison of general characteristics and biochemical parameters between the MS group and the control group in Korean-Chinese and Han-Chinese populations

Table 1 presents the characteristics of subjects by ethnicity and MS prevalence. Korean-Chinese subjects with MS showed significantly higher BMI, WC, SBP, DBP, FPG, TG, AST, ALT, GGT SUA, WBC, and LCN2 levels and lower HDL, TBIL, DBIL, and A/G levels than those in the control group. Similarly, in Han-Chinese subjects, BMI, WC, SBP, DBP, FPG, TG, AST, ALT, GGT SUA, ALB, WBC, and LCN2 levels were significantly higher, and HDL, TBIL, DBIL, and A/G were lower in the MS group than in the control group.

Table 1.

Anthropometric and Metabolic Characteristics of Subjects

	Korean-Chinese		Han-Chinese
Characteristics	Non-MS (n = 253)	MS(n = 253)	Non-MS(n = 354)	MS(n = 354)
Age	50.37 ± 10.42	50.90 ± 10.78	47.55 ± 10.88^b	47.90 ± 11.17^b
BMI	24.15 ± 2.92	26.98 ± 3.08^a	24.63 ± 3.18	27.68 ± 3.20a ^, b
WC	85.93 ± 8.73	94.07 ± 7.22^a	87.22 ± 9.00	96.22 ± 7.97a ^, b
SBP	124.81 ± 19.60	140.42 ± 18.23^a	123.02 ± 17.16	134.45 ± 18.81a ^, b
DBP	78.23 ± 11.61	88.34 ± 11.98^a	76.90 ± 11.13	85.14 ± 12.88a ^, b
FPG	5.70 ± 1.54	6.67 ± 2.08^a	5.41 ± 0.94^b	6.64 ± 2.38^a
CHO	5.09 ± 0.93	5.23 ± 1.11	4.82 ± 0.88^b	5.12 ± 0.99
TG	0.37 ± 0.12	0.56 ± 0.16^a	0.35 ± 0.10^b	0.55 ± 0.16^a
LDL	2.86 ± 0.70	2.83 ± 0.76	2.70 ± 0.65^b	2.83 ± 0.75
HDL	1.44 ± 0.34	1.15 ± 0.28^a	1.37 ± 0.30^b	1.10 ± 0.26a ^, b
AST	1.32 ± 0.15	1.36 ± 0.17^a	1.28 ± 0.13^b	1.34 ± 0.16^a
ALT	1.33 ± 0.22	1.45 ± 0.22^a	1.31 ± 0.21	1.46 ± 0.22^a
GGT	1.58 ± 0.33	1.76 ± 0.32^a	1.50 ± 0.26^b	1.73 ± 0.28^a
SUA	374.77 ± 100.28	426.03 ± 107.07^a	390.30 ± 100.92	442.18 ± 101.93^a
CREA	77.03 ± 17.01	76.20 ± 15.84	79.63 ± 14.00^b	80.37 ± 16.31^b
BUN	5.86 ± 1.43	5.96 ± 1.41	6.34 ± 1.44^b	6.17 ± 1.31
TP	73.08 ± 3.59	74.07 ± 3.80	72.92 ± 3.58	74.40 ± 3.91
ALB	49.17 ± 2.57	49.14 ± 2.70	48.95 ± 2.63	49.47 ± 2.51^a
TBIL	1.20 ± 0.16	1.16 ± 0.17^a	1.18 ± 0.16	1.16 ± 0.17
DBIL	0.72 ± 0.18	0.66 ± 0.20^a	0.70 ± 0.18	0.67 ± 0.20^a
A/G	0.32 ± 0.11	0.30 ± 0.11^a	0.31 ± 0.07	0.30 ± 0.08^a
WBC	5.94 ± 1.53	7.01 ± 2.04^a	6.48 ± 1.65^b	7.05 ± 1.76^a
LCN2	3.36 ± 0.55	3.59 ± 0.34^a	3.54 ± 0.43^b	3.65 ± 0.36a ^, b
Smoke, n (%)	99 (39.1)	108 (42.7)	137 (38.7)	158 (44.6)
Drink, n (%)	146 (57.7)	149 (58.9)	156 (44.1)	164 (46.3)

Significance at 0.05 level compared between MS and non-MS groups within same nationality using t-test.

Significance at 0.05 level when compared between different nationality groups within the same MS or non-MS group using t-test.

MS, metabolic syndrome; A/G, albumin globulin ratio; ALB, albumin; ALT, aspartate aminotransferase; AST, alanine aminotransferase; BUN, blood urea nitrogen; CHO, cholesterol; CREA, creatinine; DBIL, direct bilirubin; DBP, diastolic blood pressure; FPG, fasting plasma glucose; GGT, gamma-glutamyl transpeptidase; HDL, high-density-lipid cholesterol; LCN2, lipocalin-2; LDL, low-density-lipid cholesterol; SBP, systolic blood pressure; SUA, serum urinary acid; TBIL, total bilirubin; TG, triglyceride; TP, total protein; WBC, white blood cell count.

Notes: TG, AST, ALT, GGT, TBIL, DBIL, and LCN2 were log-ranked and turned into normally distributed data.

Comparison of LCN2 concentrations in subcomponents of MS in Korean-Chinese and Han-Chinese individuals

Stratification analysis by ethnicity and MS components showed that Korean-Chinese individuals with high WC had significantly higher LCN2 concentrations than those with normal WC. Similar results were also observed in the hypertensive, high FPG, high TG, lower HDL groups and BMI ≥25 groups. In the Han-Chinese subjects, significantly higher LCN2 concentrations were observed only in the high WC, high TG, low HDL groups and BMI ≥25 groups (Table 2).

Table 2.

Serum LCN2 Concentrations in Korean-Chinese and Han-Chinese Individuals with Different MS Components

		Korean-Chinese	Han-Chinese
WC	High WC	3.54 ± 0.43^a	3.64 ± 0.38^a
	Control group	3.38 ± 0.51	3.51 ± 0.43
BP	Hypertension	3.54 ± 0.37^a	3.60 ± 0.40
	Control group	3.38 ± 0.57	3.59 ± 0.41
FPG	Elevated glucose	3.57 ± 0.37^a	3.58 ± 0.39
	Control group	3.43 ± 0.50	3.60 ± 0.40
TG	High TG	3.58 ± 0.37^a	3.64 ± 0.38^a
	Control group	3.36 ± 0.54	3.55 ± 0.42
HDL	Low HDL	3.62 ± 0.33^a	3.66 ± 0.39^a
	Control group	3.43 ± 0.50	3.56 ± 0.41
BMI	BMI ≥ 25	3.52 ± 0.45^a	3.62 ± 0.39^a
	Control group	3.42 ± 0.49	3.55 ± 0.42

Significance at 0.05 level.

BP, blood pressure; FPG, fasting plasma glucose; HDL, high-density-lipid cholesterol; TG, triglyceride; WC, waist circumference.

In Korean-Chinese, the concentration of LCN2 showed positive correlation with WC, SBP, DBP, TG, AST, ALT, GGT, SUA, BUN, CREA, and white blood cell (WBC) counts. In Han-Chinese, serum LCN2 concentrations were positively correlated with age, BMI, WC, TG, GGT, SUA, BUN, CREA, and WBC counts. Moreover, LCN2 concentrations were negatively correlated with HDL in Han-Chinese individuals. Similar results were also found in Korean-Chinese patients (Table 3).

Table 3.

Correlation between Serum LCN2 Concentrations and Anthropometric and Metabolic Characteristics in Subjects

	Korean-Chinese		Han-Chinese
	r	P	r	P
Age	0.084	0.059	0.075	0.047
BMI	0.171	<0.001	0.090	0.017
WC	0.255	<0.001	0.160	<0.001
SBP	0.140	0.002	0.034	0.362
DBP	0.147	0.001	0.004	0.921
FPG	0.081	0.070	0.011	0.766
CHO	−0.055	0.213	0.007	0.854
TG	0.255	<0.001	0.134	<0.001
LDL	−0.037	0.405	−0.034	0.371
HDL	−0.315	<0.001	−0.132	<0.001
AST	0.104	0.019	0.026	0.491
ALT	0.190	<0.001	0.051	0.175
GGT	0.157	<0.001	0.082	0.029
SUA	0.199	<0.001	0.201	<0.001
CREA	0.167	<0.001	0.139	<0.001
BUN	0.167	<0.001	0.147	<0.001
TP	−0.031	0.481	−0.011	0.763
ALB	−0.030	0.496	−0.034	0.370
TBIL	−0.064	0.153	0.017	0.646
DBIL	0.000	0.996	0.056	0.136
A/G	0.019	0.663	−0.024	0.523
WBC	0.280	<0.001	0.182	<0.001

WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; CHO, cholesterol; TG, triglyceride; AST, alanine aminotransferase; ALT, aspartate aminotransferase; SUA, serum urinary acid; CREA, creatinine; BUN, blood urea nitrogen; TP, total protein; ALB, albumin; TBIL, total bilirubin; DBIL, direct bilirubin; A/G, albumin globulin ratio; WBC, white blood cell count.

Association analysis of LCN2 concentrations in MS of Korean-Chinese and Han-Chinese patients

According to the receiver operating characteristic curve analysis results of LCN2 for the diagnosis of MS, the cutoff value was 3.1448 mg/mL (sensitivity 71.3%, specificity 42.5%), and the area under the curve was 0.585 [95% confidence interval (CI): 0.553–0.617].

To further assess the association between LCN2 and the incident risk of MS, logistics analysis was performed in both the high-LCN2 and low-LCN2 groups divided by 3.1448 mg/mL. In Korean-Chinese patients, the risk of MS in the high LCN2 group was nearly 2.339 times higher than that in the low LCN2 group (95% CI: 1.632–3.352) in the unadjusted model, whereas in Han-Chinese patients, it was 1.523 (95% CI: 1.101–2.108). To better examine the effect of LCN2 in MS, we adjusted for several confounding factors. After adjustment for WC, SBP, DBP, FPG, TG, HDL, AST, ALT, GGT, SUA, TBIL, DBIL, A/G, and WBC count, the risk of developing MS remained in Korean-Chinese subjects, with an odds ratio (OR) of 1.818 (95% CI: 1.031–3.207). In contrast, the risk of MS was absent in Han-Chinese subjects after we adjusted for WC, SBP, DBP, FPG, TG, HDL, AST, ALT, GGT, SUA, ALB, DBIL, A/G, and WBC count (Table 4).

Table 4.

Risk and 95% CI of MS in Korean-Chinese and Han-Chinese Patients with Higher LCN2 Concentrations

		B	SE	Wald	OR (95% CI)
Korean-Chinese	Model 1	0.850	0.184	21.403	2.339 (1.632–3.352)
	Model 2	0.676	0.228	8.818	1.966 (1.258–3.071)
	Model 3	0.640	0.281	5.179	1.8.97 (1.093–3.293)
	Model 4	0.598	0.290	4.266	1.818 (1.031–3.207)
Han-Chinese	Model 1	0.421	0.166	6.452	1.523 (1.101–2.108)
	Model 2	0.291	0.207	1.970	1.337 (0.891–2.007)
	Model 3	0.025	0.270	0.008	1.025 (0.604–1.739)
	Model 4	0.023	0.281	0.007	1.024 (0.591–1.774)

Model 1: unadjusted; Model 2: adjusted for WC, SBP, DBP, and FPG; Model 3: Model 2+ TG, HDL, AST, ALT, GGT, SUA; Model 4: Model 3 + TBIL, DBIL, A/G, and WBC (In Korean-Chinese); Model 3: ALB, DBIL, A/G, and WBC (In Han-Chinese).

CI, confidence interval; SE, standard error; OR, odds ratio.

Discussion

In parallel to the rapid increase in socioeconomic level and alterations in lifestyle and dietary habits of residents, China has experienced a steady increase in the prevalence of MS. According to nationwide studies, the prevalence of MS reached 24.2% in 2012 and 33.9% in 2017.^2,3 Several recent studies showed that the incidence and development of LCN2 was closely associated with various adipokines secreted by human adipose tissue and that chronic inflammatory status, impaired pancreatic function, and endothelial dysfunction could also induce the pathogenesis of MS.²⁸

As a manifestation of nutrition overloading, it could consequently induce adipose tissue expansion and alter the release of adipokines. Studies have shown that visceral white adipose tissue enlargement is closely associated with obesity.^29
–31 It has been demonstrated that LCN2 is produced by adipose tissue,^32,33 and its production can be increased after the maturation of preadipose tissue to mature adipose tissue.³⁴ Several previous in vitro studies and experiments using obesity models have demonstrated the increased expression of LCN2 mRNA in adipose tissue.^34
–36 Other studies based on obese populations have shown that circulating LCN2 concentrations were significantly higher than those in the control group and were closely associated with BMI and WC.^37,38 Wang et al.³⁶ showed that circulating concentrations of LCN2 were significantly higher in the BMI ≥30 kg/m² group than in the BMI <23 kg/m² group and were positively correlated WC and BMI. In the present study, the concentrations of LCN2 were positively correlated with WC and BMI in both Korean-Chinese and Han-Chinese populations. It has been demonstrated that LCN2 is the key regulator of peroxisome proliferator activated receptor-γ (PPAR-γ), and the latter has been shown to participate in insulin sensitization and lipid metabolism.³⁹ Zhang et al.³⁴ showed that LCN2 could inhibit the secretion of PPAR-γ in adipocytes and macrophages, and the downregulation of PPAR-γ could also limit the use of lipids, which results in endothelial dysfunction and dyslipidemia. The study performed by Wallenius et al.⁴⁰ showed that LCN2 was positively correlated with TG and inversely correlated with HDL in metabolically healthy male subjects. Similar results were also observed in the present study. However, the exact underlying pathophysiological mechanism of LCN2 involvement in lipid metabolism still needs to be determined.

Peripheral IR is often accompanied by an increased concentration of LCN2, which increases blood glucose by promoting inflammatory pathways and inhibiting insulin signaling pathways. However, the improvement of insulin sensitivity, manifested as decreases in blood glucose and insulin concentrations, is observed in LCN2 knockout mice.^16,41
–43 In our subgroup study of MS components, an increased concentration of LCN2 was detected only in Korean-Chinese patients with hyperglycemia. Clinical experiments performed by Huang et al.⁴⁴ confirmed that serum LCN2 concentrations in subjects with impaired fasting glucose and glucose tolerance were significantly higher than those in subjects with normal glucose, reflecting that elevated LCN2 was associated with an increased risk of impaired glucose regulation. However, in a cross-sectional study of 58 volunteers, LCN2 was not significantly associated with IR.⁴⁵ Further experimental and large-scale studies are needed to unravel the mechanism of the observed controversial association to gain more knowledge into the role in obesity and glucose metabolism.

Regarding the risk of MS incidence among ethnic groups, we found that the risk of MS incidence in Korean-Chinese patients with high LCN2 was 2.339 (95% CI: 1.632–3.352) compared with the low LCN2 group. After adjusting for WC, SBP, DBP, FPG, TG, HDL, AST, ALT, GGT, SUA, TBIL, DBIL, A/G, and WBC, the risk remained with an OR of 1.818 (95% CI: 1.031–3.207). Interestingly, the risk of MS incidence in Han-Chinese with high LCN2 was 1.523 (95% CI: 1.101–2.108), but after the adjustment for WC, SBP, DBP, FPG, TG, HDL, AST, ALT, GGT, SUA, ALB, DBIL, A/B, and WBC, the risk was absent. This gap indicates that there are ethnic differences in the risk of MS, and the predictive effect of LCN2 concentrations on MS in Korean-Chinese individuals is stronger than that in Han-Chinese individuals.

Yanbian Korean Autonomous Prefecture is located in the northeast border area of China. It has a cold climate, and the living habits and genetic background of Korean-Chinese are different from those of the Han population. It is believed to result from the following two reasons: 1) Differences in living habits: according to statistics, Korean-style eating habits include higher fat and salt intakes,⁴⁶ drinking rates,⁴⁷ and smoking rates⁴⁸ than those of Han people. 2) Genetic environment differences: The different distribution characteristics of genetic susceptibility genes such as ApM1 gene, PPARY gene and apolipoprotein B gene in minority regions may be one of the reasons for the ethnic differences in the prevalence of MS.^49,50 Recently, several studies focused on the genetic diversity of residents in Yanbian revealed that single nucleotide polymorphisms (SNPs) might contribute to the metabolic diversities between Korean and Han populations. For example, phosphoenolpyruvate carboxykinase-1 (PCK1) participates in glucose metabolism, and the genotype of the PCK1 SNP rs1042531 site in Korean nationality resulted in a significant difference in the mean concentrations of HDL-C (P < 0.05); at the same time, differences in BMI, WC, SBP, DBP and FBG were observed in those with Han nationality.⁵¹ In addition, it has been observed that various members of the lipocalin superfamily, including adiponectin gene SNP rs17846872 related to lipid metabolism and the nitric oxide synthase 3 gene SNP rs3918227 associated with blood pressure regulation exhibit correlations with BMI, WC, TGs, TC, and other metabolic indicators or blood pressure levels. Furthermore, there are ethnic differences between Korean and Han populations in the Yanbian region.^52,53

The difference in MS risk between Korean and Han populations may be affected by the interaction of environmental and genetic factors at the same time, but for the exact role of LCN2 in MS risk, in addition to the use of traditional biochemical indicators in future research, further genetic analysis of the study population may be more helpful to reveal the differences in the distribution characteristics of MS in minority areas.

Our research has certain limitations. First, the method of cross-sectional design cannot be used to determine a causal relationship; it can only analyze the correlation. Second, because of the lack of sensitive index data such as insulin concentrations, HOMA-IR, inflammatory factors, and more comprehensive sociodemographic characteristics in this study. Therefore, prospective research needs to further include residents in other regions of China to explore the role of LCN2 in MS.

Conclusions

In conclusion, we revealed that elevated circulating LCN2 was associated with the increased incidence of MS, and this effect in Korean-Chinese individuals was stronger than that in Han-Chinese individuals.

Footnotes

Acknowledgments

The authors thank all participants for their participation. The authors are further indebted to The Medical School of Yanbian University for the support.

Authors’ Contributions

Z.Q. offered experiment resources, conceived and designed the experiments. S.Z. performed the experiments, coordinated the study, performed data analysis, and drafted the article; Y.T. and S.Y. contributed to draft the article; Z.Q. contributed to statistical analysis; Z.Q. reviewed and edited the article. All authors have read and agreed to the published version of the article.

Ethics Statement

The studies involving human participants were reviewed and approved by the Ethics Committee of Yanbian University (20230975). The patients/participants provided their written informed consent to participate in this study.

Author Disclosure Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding Information

This work was supported by the National Natural Science Foundation of China (Grant No. 81660562).

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