Assessment of the biological variation of plasma tissue inhibitor of metalloproteinases-1

C.B. Frederiksen, Anne Fog Lomholt, Tine Lottenburger, G.J. Davis, B.L. Dowell, M.A. Blankenstein, Ib Jarle Christensen, Nils Brunner, H.J. Nielsen, Camilla Frederiksen, A F Lomholt, T Lottenburger, G J Davis, B L Dowell, M A Blankenstein, Ib Jarle Christensen, N Brunner, Hans Jørgen Nielsen

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Abstract

BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret the utility of TIMP-1 in CRC. The aim of this study was to establish the biological and analytical variation of plasma TIMP-1 in volunteers. MATERIAL AND METHODS: Three separate studies were undertaken. 1: Plasma was collected from 23 volunteers 6 times within a 3-week period, first in September 2004 (round [R] 1), then repeated in May 2005 (R2) and May 2006 (R3) in the same group of individuals. TIMP-1 levels were determined by the MAC15 ELISA assay and with the Abbott ARCHITECT i2000 Immunoanalyzer. 2: Circadian variation was evaluated in plasma collected 7 times within a 24-hour period (n=16). 3: Effects of physical exercise were evaluated in plasma collected before and after bicycling (n=14). In studies 2 and 3 TIMP-1 levels were determined with the MAC15 ELISA assay only. RESULTS: A significant correlation between TIMP-1 MAC15 and ARCHITECT i2000 was shown (rs=0.78, p<0.002), with consistently higher levels being detected by the ARCHITECT i2000. Median levels of TIMP-1 (ARCHITECT) at 8 a.m. in each round were 74.9 ng/mL (range 65.7-89.9) (R1), 87.3 ng/mL (range 72.7-127.9) (R2), and 81.9 ng/mL (range 66.8-113.6) (R3). The within-subject variation was 10.7%, the variation between rounds was 7.4%, and the intraclass correlation was 46.2%. Comparison between the 3 rounds and time of collection showed that TIMP-1 values decreased by 11% after storage for more than 16 months (p=0.0002). A systematic circadian variation in plasma TIMP-1 levels was not observed (p=0.17). No significant variation of plasma TIMP-1 was found in relation to physical exercise (p=0.92 [global test]). CONCLUSION: Levels of plasma TIMP-1 in volunteers show limited circadian, day-to-day, week-to-week and season-to-season variation. In addition, physical exercise has no impact on plasma TIMP-1 levels. Possible storage-dependent decreases in plasma TIMP-1 levels warrant further investigation.
Original languageEnglish
JournalInternational Journal of Biological Markers
Volume23
Issue number1
Pages (from-to)42-7
Number of pages5
ISSN0393-6155
Publication statusPublished - 2008

Bibliographical note

Keywords: Adult; Aged; Analysis of Variance; Blood Chemical Analysis; Circadian Rhythm; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Exercise; Female; Humans; Immunoassay; Male; Middle Aged; Reference Values; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Tumor Markers, Biological

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