Reference intervals for serum apolipoproteins A-I, A-II, B, C-II, C-III, and E in healthy Japanese determined with a commercial immunoturbidimetric assay and effects of sex, age, smoking, drinking, and Lp(a) level

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Abstract

Background: Apolipoproteins, which are contained in lipoprotein particles, play important roles in the transport of lipids. Methods: Serum levels of apolipoproteins (apo) A-I, A-II, B, C-II, C-III, and E were determined by immunoturbidimetry in a healthy Japanese study population (1018 men and 1167 women, age 20–69 years) to establish reference intervals. Results: Among the 2185 subjects examined, the mean serum value for apoA-I was 1.42±0.20 g/l, for apoA-II was 0.30±0.05 g/l, for apoB was 0.87±0.18 g/l, for apoC-II was 29±13 mg/l, for apoC-III was 75±20 mg/l, and for apoE was 36±9 mg/l. A sex difference was detected in the mean serum concentrations of all six apolipoproteins. Alcohol consumption and cigarette use had a slight effect on serum apolipoprotein concentrations. Age effects were observed among women in apoB, apoC-II, and apoC-III concentrations. Moreover, individuals with elevated serum lipoprotein (a) [Lp(a), >300 mg/l] also displayed increased serum apoB and apoC-II levels and an increased apoB/apoA-I ratio. Conclusion: The reference intervals for apolipoproteins in Japanese adults that we established, using commercially available reagents for automated analyzers, will be helpful for assessing risk of coronary heart disease and pathological conditions of patients with hyperlipidemia. We recommend use of these reference intervals for the clinical interpretation of serum apolipoprotein concentrations.

Introduction

Epidemiologic studies indicate that serum apolipoprotein concentrations and risk of coronary heart disease (CHD) are related [1], [2], [3], [4], [5]. High serum concentrations of apoB, a protein component of low-density lipoprotein (LDL), are associated with increased risk of CHD, and concentrations of apoA-I, a major protein component of high-density lipoprotein (HDL), are inversely associated with CHD risk. In addition to serum concentrations, the apoB to apoA-I ratio (apoB/apoA-I) can also be a marker for CHD [6], [7].

Apolipoproteins that can be used in routine clinical laboratory tests include apoA-I, apoA-II, apoB, apoC-II, apoC-III, and apoE, and all of which can be assayed by immunoturbidimetric assay [8], [9], [10], immunonephelometry [11], single radial immunodiffusion [12], [13], and enzyme-linked immunosorbent assay [14], [15]. Despite the potential clinical utility of apolipoprotein measurements, use of apolipoprotein assays has been limited because of the lack of standardization, a suitable reference database, and an automated assay suitable for use in routine clinical laboratory tests. The World Health Organization (WHO) and the International Federation of Clinical Chemistry (IFCC) have collaborated to develop reference material to ensure comparability between laboratories and manufacturers [16], [17], [18]. A recent study established reference intervals for apoA-I and apoB using WHO-IFCC reference materials and a traceable measurement system [19], [20], [21]. Moreover, the STANISLAS cohort study [22], which was a large-scale epidemiologic investigation, established reference intervals for apoE.

Here, we report reference intervals for apoA-I, apoA-II, apoB, apoC-II, apoC-III, and apoE in healthy Japanese adults for use with commercially available reagents for automated analyzers. Sex and age-related differences were taken into account.

Section snippets

Subjects and sample collection

The subjects, recruited from 14 different sites throughout Japan, were 2185 Japanese adults (1018 men and 1167 women) 20–69 years who had not been treated with hyperlipidemia drugs, tricyclic drugs, or long-term steroids. The subjects met the following criteria: total serum cholesterol level between 1.20 and 2.20 g/l, serum triglyceride level between 0.50 and 1.50 g/l, and HDL-cholesterol level of not less than 0.40 g/l. The study participants were selected from among 4170 recruited patients

Results

The mean concentrations of apolipoproteins for the 2185 samples collected from the 14 participating institutions are shown in Table 1. A sex difference was detected for the apolipoprotein concentrations. ApoA-I and apoE levels were higher in women, whereas apoA-II, apoB, apoC-II, and apoC-III levels were higher in men (Table 1). The apolipoprotein concentrations are shown according to age in Table 2. ApoA-I was higher in women than in men in all age categories, and no significant age-related

Discussion

Numerous comparative epidemiologic studies have been conducted concerning apolipoproteins and their respective parent lipoproteins in association with CHD. There has been particular interest in apolipoprotein associations with HDL and LDL; both apoA-I and apoB levels reflect the relation between their parent lipoproteins and the risk for CHD [2], [3], [4], [5], [6], [7], [19], [20], [21], [22], [24], [25], [26].

In both men and women, we found age-related changes in apoB, apoC-II, and apoC-III;

Acknowledgements

The authors gratefully acknowledge the valuable assistance of Kazunori Saito, Shigeru Koizumi, Hideo Igarashi, Osamu Sato, and Haruo Yamakami of Daiichi Pure Chemicals.

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