Abstract
Background: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality.
Methods: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA).
Results: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI.
Conclusions: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.
Acknowledgments
This study was supported by Research Fund of Uludag Universty (UAP(T)-2011/48), IFCC C-RIDL, Scientific Research Fund (No:24256003:2012-2014) provided by the Japan Society for the Promotion of Science, Abbott Diagnostics and Becton Dickinson. We had invaluable input from the IFCC C-RIDL and the Turkish National Biochemical Association. We are very grateful to Uludag University Central Laboratory, We are thankful to David Ambruster from Abbott Diagnostics for his kind cooperation to realize this study. The final manuscript was edited with generous support by Prof. A. Myron Johnson.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
References
1. Horn PS, Pesce AJ. Reference intervals an update. Clin Chim Acta 2003;334:5–23.10.1016/S0009-8981(03)00133-5Search in Google Scholar
2. Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation on the theory of reference values. Part 1.The concepts of reference values. Clin Chim Acta 1987;167:111–8; J Clin Chem Clin Biochem 1987;25:337–42.Search in Google Scholar
3. Petit Clerc C, Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation on the theory of reference values. Part 2. Selection of individual for the production of reference value. Clin Chim Acta 1987;170:S1–12; J Clin Chem Clin Biochem 1987;25:337–42.Search in Google Scholar
4. Solberg HE, Petit Clerc C. International Federation of Clinical Chemistry (IFCC). Approved recommendation on the theory of reference values. Part 3. Preparation of individuals and collection of the specimens for the production of reference values. Clin Chim Acta 1988;177:S3–11; J Clin Chem Clin Biochem 1988;26:593–8.Search in Google Scholar
5. Solberg HE, Stamm D. International Federation of Clinical Chemistry (IFCC). Approved recommendation on the theory of reference values. Part 4. Control of analytical variation in the production, transfer and application of reference values. Clin Chim Acta 1991;202:S5–11; J Clin Chem Clin Biochem 1991;29:531–5.Search in Google Scholar
6. Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation on the theory of reference values. Part 5. Statistical treatment of collected reference values. Clin Chim Acta 1987;170:S13–32; J Clin Chem Clin Biochem 1987;25:645–56.Search in Google Scholar
7. Dybkaer R, Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation on the theory of reference values. Part 6. Presentation of observed values related to reference values. Clin Chim Acta 1987;170:S33–42; J Clin Chem Clin Biochem 1987;25:657–62.Search in Google Scholar
8. CLSI and IFCC, C28-A3 document; Defining, establishing and verifying reference intervals in the clinical laboratory: approved guideline, 3rd ed., 2008;28:1–76.Search in Google Scholar
9. Ceriotti F, Hinzmann R, Panteghini M. Reference intervals: the way forward. Ann Clin Biochem 2009;46:8–17.10.1258/acb.2008.008170Search in Google Scholar
10. Directive 98/79/EC of European Parliamant and the Council of 27 October 1998 ON invitro diagnostic medical devices. Offical J Eur Commun 7 December 1998; L331/1–L331/37.Search in Google Scholar
11. International Organization for Standardization. ISO 15189:2012 Medical laboratories – Requirements for quality and competence, 3rd ed., 2012.Search in Google Scholar
12. Ceriotti F. Common reference intervals the IFCC position. Clin Biochem 2009;42:297.10.1016/j.clinbiochem.2008.09.017Search in Google Scholar
13. Ozarda Y, Ichihara K, Barth JH, Klee G, and on behalf of the CRIDL on Reference intervals and Decision Limits, IFCC. Protocol and standard operating procedures for common use in wordwide multicenter study on reference values. Clin Chem Lab Med 2013;51:1027–40.10.1515/cclm-2013-0249Search in Google Scholar
14. Ichihara K, Ozarda Y, Klee G, Straseski J, Barth JH, Baumann N, et al. Utility of panel of sera for alignment of test results in the worldwide multicenter study on reference values. Clin Chem Lab Med 2013;51:1007–20.10.1515/cclm-2013-0248Search in Google Scholar
15. Ozarda Ilcol Y, Aslan D. Determining reference value of blood chemistry profile in healthy subjects in Bursa. Turk J Biochem 2004;29:183–92.Search in Google Scholar
16. Ozarda Ilcol Y, Aslan D. Use of patient data for indirect estimation of reference intervals for clinical chemical anaytes in Turkey. Clin Chem Lab Med 2006;44:867–76.Search in Google Scholar
17. Ozarda Y, Sucu DK, Hizli B, Aslan D. Rate of T alleles and TT genotype at MTHFR 677C->T locus or C alleles and CC genotype at MTHFR 1298A->C locus among healthy subjects in Turkey: impact on homocysteine and folic acid status and reference intervals. Cell Biochem Func 2009;27:568–77.10.1002/cbf.1610Search in Google Scholar
18. Inal TC, Serteser M, Coskun A, Ozpinar A, Unsal I. Indirect reference intervals estimated from hospitalized population for throtropin annd free thyroxine. Croat Med J 2010;51:124–30.10.3325/cmj.2010.51.124Search in Google Scholar
19. Koseoglu M, Isleten F, Dursun S, Cuhadar S. Determination of reference intervals of healthy adults aged between 20–50 years in Izmir. Turk J Biochem 2004;35:215–24.Search in Google Scholar
20. Ichihara K. Statistical considerations for harmonization of the global multicenter study on reference values. Clin Chim Acta 2014;432:108–18.10.1016/j.cca.2014.01.025Search in Google Scholar
21. Ricos C, Alverez V, Cava F, Garcia-Lario CV, Hernandez A, Jimenez CV, et al. Current data bases on biyologic variation: pros, cons and progress. Scand J Clin Lab Invest 1999;59:491–500.10.1080/00365519950185229Search in Google Scholar
22. Ichihara K, Boyd J. An appraisal of statistical procedures used in derivation of reference intervals. Clin Chem Lab Med 2010;48:1537–51.10.1515/CCLM.2010.319Search in Google Scholar
23. Yamamato Y, Hosogaya S, Osawa S, Ichıhara K, Onuma T, Saito A, et al. Nationwide multicenter study aimed at the establishment of common reference intervals for standardized clinical laboratory tests in Japan. Clin Chem Lab Med 2013;51:1–10.10.1515/cclm-2012-0413Search in Google Scholar
24. Ichihara K, Ceriotti F, Tam TH, Sueyoshi S, Poon PM, Thong ML, et al. The Asian project for collaborative derivation of reference intervals: (1) strategy and major results of standardized analytes. Clin Chem Lab Med 2013;48:1593–601.10.1515/cclm-2012-0421Search in Google Scholar
25. Ceriotti F. Prerequisites for use of common reference intervals. Clin Biochem Rev 2007;28:115–21.Search in Google Scholar
26. Mahley RW, Palaoglu EK, Atak Z, Dawson-Pepin J, Langlois AM, Cheung V, et al. Turkish Heart Study: lipids, lipoproteins, and apolipoproteins. J Lipid Res 1995;36:839–59.10.1016/S0022-2275(20)40067-7Search in Google Scholar
27. Onat A. Risk factors and cardiovascular disease in Turkey. Aterosclerosis 2001;156:1–10.10.1016/S0021-9150(01)00500-7Search in Google Scholar
28. Bersot TP, Vega GL, Grundy SM, Paloglu EK, Atagündüz P, Ozbayrakçi S, et al. Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population. J Lipid Res 1999;40:432–8.10.1016/S0022-2275(20)32447-0Search in Google Scholar
29. Mahley RW, Pepin J, Paloglu EK, Malloy MJ, Kane JP, Bersot TP. Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase activity: high density lipoprotein characterization and gender specific effects of apoprotein E genotype. J Lipid Res 2000;41:1290–301.10.1016/S0022-2275(20)33437-4Search in Google Scholar
30. Onat A, Can G, Hergenç G, Uğur M, Yüksel H. Coronary disease risk prediction algorithm warranting incorporation of C-reactive protein in Turkish adults, manifesting sex difference. Nutr Metab Cardiovasc Dis 2012;22:643–50.10.1016/j.numecd.2010.10.010Search in Google Scholar
31. Mahley RW, Can S, Ozbayrakci S, Bersot TP, Tanir S, Palaoglu KE, et al. Modulation of high-density lipoproteins in a population in Istanbul, Turkey with low levels of high-density lipoproteins. Am J Cardiol 2005;96:547–55.10.1016/j.amjcard.2005.04.018Search in Google Scholar
32. Yadav D, Gupta M, Mishra S, Sharma P. Reference interval for lipid profile in North Indian population from Rajasthan according to various partitioning criteria. Clin Chim Acta 2013;426:145–51.10.1016/j.cca.2013.06.004Search in Google Scholar
33. Wang XJ, Xu GB, Li HX, Liu Y, Wang F. Reference intervals for serum creatinine with enzymatic assay and evaluation of four equations to estimate glomerular filtration rate in a healthy Chinese adult population. Clin Chim Acta 2011;412:1793–7.10.1016/j.cca.2011.05.033Search in Google Scholar
34. Mazzachi BC, Peake MJ, Ehrhardt V. Reference range and method comparison studies for enzymatic and Jaffe creatinine assays in plasma and serum and early morning urine. Clin Lab 2000;46:53–5.Search in Google Scholar
35. Rustad P, Felding P, Franzson I, Kairisto V, Lahti A, Mårtensson A, et al. The Nordic Reference Interval Project 2000: recommended reference intervals for 25 common biochemical properties. Scand J Clin Lab Invest 2004;64:271–84.10.1080/00365510410006324Search in Google Scholar
36. Mårtensson A, Rustad P, Lund H, Ossowicki H. Creatininium reference intervals for corrected methods. Scand J Clin Lab Invest 2004;64:439–42.10.1080/00365510410002832Search in Google Scholar
37. Junge W, Wilke B, Halabi A, Klein G. Determination of reference intervals for serum creatinine, creatinine excretion and creatinine clearance with an enzymatic and a modified Jaffe method. Clin Chim Acta 2004;344:137–48.10.1016/j.cccn.2004.02.007Search in Google Scholar
38. Ceriotti F, Boyd JC, Klein G, Henny J, Queraltó J, Kairisto V, et al.; IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem 2008;54:1261.10.1373/clinchem.2007.099648Search in Google Scholar
39. Ceriotti F, Henny J, Queraltó J, Ziyu S, Ozarda Y, Chen B, et al. IFCC Committee on Reference Intervals and Decision Limits (C-RIDL); Committee on Reference Systems for Enzymes (C-RSE). Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study. Clin Chem Lab Med 2010;48:1593–601.10.1515/CCLM.2010.315Search in Google Scholar
40. Lo YC, Armbruster DA. Reference intervals of common clinical chemistry analytes for adults in Hong Kong. eJIFCC, 2012. Available from: http://www.ifcc.org/ifcc-communications-publications-division. Accessed on 13 June, 2013.Search in Google Scholar
Supplemental Material
The online version of this article (DOI 10.1515/cclm-2014-0228) offers supplementary material, available to authorized users.
©2014 by De Gruyter