Abstract
Carbohydrate deficient transferrin (CDT) is one of the conventional markers for chronic alcohol consumption, is used by researchers and clinicians. A number of enzymes are affected by ethanol intake. The induction or inhibition of sialyl transferase and plasma sialidase may be involved in the CDT level elevation. An alteration of protein transport during post-translational modification could be a primary mechanism in the impairment of protein metabolism associated with chronic alcohol abuse. Transferrin being a steroid responsive protein, sex-based hormonal variations might contribute to the lower sensitivity of CDT. Varying hormonal statuses such as pregnancy, use of contraceptives, menopause/ menstrual cycle can alter iron homeostasis in women. CDT levels are markedly affected by iron homeostasis. Several CDT assay methods appeared promising, but it is not readily apparent which technique is the most accurate. Moreover, false-positive results of CDT have been reported in non-alcohol related hepatic failure and in rare conditions. Therefore clinical interpretation of CDT needs careful assessment in patients with alcohol-related or non-alcohol-related health disorders.
Key Words: Carbohydrate deficient transferrin (CDT), Transferrin, Alcohol, Marker, Iron homeostasis
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References
- 1.Stibler H., Kjellin K.G. Isoelectric focusing and electrophoresis of the CSF proteins in tremor of different origins. J. Neurol. Sci. 1976;30:269–285. doi: 10.1016/0022-510X(76)90133-7. [DOI] [PubMed] [Google Scholar]
- 2.Stibler H. Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful alcohol consumption reviewed. Clin. Chem. 1991;37:2029–2037. [PubMed] [Google Scholar]
- 3.Sillanaukee P., Strid N., Allen J.P., Litten R.Z. Possible reasons why heavy drinking increases carbohydrate-deficient transferrin. Alcoholism Clin. Exp. Res. 2001;25:34–40. doi: 10.1111/j.1530-0277.2001.tb02124.x. [DOI] [PubMed] [Google Scholar]
- 4.Aisen P., Listowsky I. Iron transport and storage proteins. Ann. Rev. Biochem. 1980;7:357–393. doi: 10.1146/annurev.bi.49.070180.002041. [DOI] [PubMed] [Google Scholar]
- 5.Putnam F. W. Transferrin. In: Putnam F.W., editor. The Plasma Proteins: Structure, Function, and Genetic Control. 2nd Ed. San Diego: Academic Press; 1975. pp. 58–131. [Google Scholar]
- 6.MacGillivray R.T.A., Mendez E., Shewale J.G., Sinha S.K., Lineback-Zing J., Brew K. The primary structure of human serum transferrin. The structure of seven cyanogen bromide fragments and the assembly of the complete structure. J. Biol. Chem. 1983;258:3543–3553. [PubMed] [Google Scholar]
- 7.Noort W.L., Jong G., Eijk H.G. Purification of isotransferrins by concanavalin A Sepharose chromato-graphy and preparative isoelectric focusing. Eur. J. Clin. Chem. Clin. Biochem. 1994;32:885–892. doi: 10.1515/cclm.1994.32.12.885. [DOI] [PubMed] [Google Scholar]
- 8.Eijk H.G., Noort W.L., Jong G., Koster J.F. Human serum sialo transferrins in diseases. Clin. Chim. Acta. 1987;165:141–145. doi: 10.1016/0009-8981(87)90157-4. [DOI] [PubMed] [Google Scholar]
- 9.Märtensson O., Härlin A., Brandt R., Seppä K., Sillanaukee P. Transferrin isoform distribution: gender and alcohol consumption. Alcohol Clin. Exp. Res. 1997;21:1710–1715. doi: 10.1111/j.1530-0277.1997.tb04512.x. [DOI] [PubMed] [Google Scholar]
- 10.Kamboh M. I., Ferrell R.E. Human transferrin polymorphism. Hum. Hered. 1987;37:65–81. doi: 10.1159/000153680. [DOI] [PubMed] [Google Scholar]
- 11.Bean P., Peter J.B. A new approach to quantify carbohydrate-deficient transferrin isoforms in alcohol abusers: Partial iron saturation in isoelectric focusing/ immunoblotting and laser densitometry. Alcohol Clin. Exp. Res. 1993;17:1163–1170. doi: 10.1111/j.1530-0277.1993.tb05222.x. [DOI] [PubMed] [Google Scholar]
- 12.Petren S., Vesterberg O., Jomvall H. Differences among five main forms of serum transferrin. Alcohol Clin. Exp. Res. 1987;11:453–456. doi: 10.1111/j.1530-0277.1987.tb01922.x. [DOI] [PubMed] [Google Scholar]
- 13.Schade A.I., Feinhart R., Levy H. Carbon dioxide and oxygen in complex formation with iron and siderophilin, the iron-binding component of human plasma. Arch. Biochem. Biophys. 1949;20:170–170. [PubMed] [Google Scholar]
- 14.Ehrenberg A., Laurell C.B. Magnetic measurements on crystallized Fetransferrin isolated from the blood plasma of swine. Acta. Chem. Scand. 1955;9:68–68. [Google Scholar]
- 15.Geffen I., Spiess M. A sialoglycoprotein receptor. Int. Rev. Cytol. 1992;137B:81–219. doi: 10.1016/s0074-7696(08)62605-4. [DOI] [PubMed] [Google Scholar]
- 16.Schachter H. Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosacharides. Biochem. Cell. Biol. 1986;64:163–181. doi: 10.1139/o86-026. [DOI] [PubMed] [Google Scholar]
- 17.Rademacher T., Parekh R.B., Dwek R.A. Glycobiology. Ann. Rev. Biochem. 1988;57:785–838. doi: 10.1146/annurev.bi.57.070188.004033. [DOI] [PubMed] [Google Scholar]
- 18.März L., Hatton M., Berry L., Recoeczi E. The structural heterogeneity of the carbohydrate moiety of desialylated human transferrin. Can. J. Biochem. 1982;60:624–630. doi: 10.1139/v82-092. [DOI] [PubMed] [Google Scholar]
- 19.Spik G., Bayard B., Fournet F., Strecker G., Bouquelet S., Montreuil J. Studies on glycoconjugates LXIV. Complete structure of two carbohydrates of human serotransferrin. FEBS Lett. 1975;50:296–299. doi: 10.1016/0014-5793(75)80513-8. [DOI] [PubMed] [Google Scholar]
- 20.Ghosh P., Okoh C., Liu Q.H., Lakshman M.R. Effects of chronic ethanol on enzymes regulating sialylation and desialylation of transferrin in rats. Alcohol Clin. Exp. Res. 1993;17:576–579. doi: 10.1111/j.1530-0277.1993.tb00802.x. [DOI] [PubMed] [Google Scholar]
- 21.Baraona E., Lieber C.S. Effects of alcohol on hepatic transport of proteins. Ann. Rev. Med. 1982;33:281–292. doi: 10.1146/annurev.me.33.020182.001433. [DOI] [PubMed] [Google Scholar]
- 22.Behrens U., Worner T.M., Braly L.F., Schaffner F., Lieber C.S. Carbohydrate-deficient transferrin, a marker for chronic alcohol consumption in different ethnic populations. Alcohol Clin. Exp. Res. 1988;12:427–432. doi: 10.1111/j.1530-0277.1988.tb00221.x. [DOI] [PubMed] [Google Scholar]
- 23.Allen J.P., Litten R.Z., Anton R.F., Cross G.M. Carbohydrate-deficient transferrin as a measure of immoderate drinking: Remaining issues. Alcohol Clin. Exp. Res. 1994;18:799–812. doi: 10.1111/j.1530-0277.1994.tb00043.x. [DOI] [PubMed] [Google Scholar]
- 24.Sillanaukee P. Laboratory markers of alcohol abuse. Alcohol Alcohol. 1996;31:613–616. doi: 10.1093/oxfordjournals.alcalc.a008199. [DOI] [PubMed] [Google Scholar]
- 25.Gronbaek M., Henriksen J.H., Becker U. Carbohydrate-deficient transferrin-A valid marker of alcoholism in population studies? Results from the Copenhagen City Heart Study. Alcohol Clin. Exp. Res. 1995;19:457–461. doi: 10.1111/j.1530-0277.1995.tb01531.x. [DOI] [PubMed] [Google Scholar]
- 26.Huseby N.E., Nilssen O., Erfurth A., Wetterling T., Kanitz R.D. Carbohydrate-deficient transferrin and alcohol dependency-Variation in response to alcohol intake among different groups of patients. Alcohol Clin. Exp. Res. 1997;21:201–205. doi: 10.1111/j.1530-0277.1997.tb03750.x. [DOI] [PubMed] [Google Scholar]
- 27.LaGrange L., Anton R.F., Crow H., Garcia S. A correlational study of carbohydrate-deficient transferrin (CDT) values and alcohol consumption among Hispanic college students. Alcohol Clin. Exp. Res. 1994;18:653–656. doi: 10.1111/j.1530-0277.1994.tb00926.x. [DOI] [PubMed] [Google Scholar]
- 28.LaGrange L., Anton R.F., Garcia S., Herrbold C. Carbohydrate-deficient transferrin levels in a female population. Alcohol Clin. Exp. Res. 1995;19:100–103. doi: 10.1111/j.1530-0277.1995.tb01476.x. [DOI] [PubMed] [Google Scholar]
- 29.Löf K., Seppä K., Itala L., Koivula T., Turpeinen U., Sillanaukee P. Carbohydrate-deficient transferrin as an alcohol marker among female heavy drinkers: A population-based study. Alcohol Clin. Exp. Res. 1994;18:889–894. doi: 10.1111/j.1530-0277.1994.tb00056.x. [DOI] [PubMed] [Google Scholar]
- 30.Stibler H., Borg S., Beckman G. Transferrin phenotype and level of carbohydrate-deficient transferrin in healthy individuals. Alcohol Clin. Exp. Res. 1988;12:450–453. doi: 10.1111/j.1530-0277.1988.tb00224.x. [DOI] [PubMed] [Google Scholar]
- 31.Anton R.F., Stout R.L., Roberts J.S., Allen J.P. The effect of drinking intensity and frequency on serum carbohydratedeficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics. Alcohol Clin. Exp. Res. 1998;22:1456–1462. doi: 10.1111/j.1530-0277.1998.tb03935.x. [DOI] [PubMed] [Google Scholar]
- 32.Helander A, Vabö E, Levin K, Borg S. Intra- and inter-individual variability of carbohydrate-deficient transferrin, ψ-glutamyl-transferase, and mean corpuscular volume in teetotalers. Clin Chem. 1998;44:2120–2125. [PubMed] [Google Scholar]
- 33.Niemela O., Sorvajarvi K., Blake J.E., Israel Y. Carbohydrate deficient transferrin: as a marker of alcohol abuse. Relationship to alcohol consumption, severity of liver disease and fibrinogenesis. Alcohol Clin. Exp. Res. 1995;19:1205–1208. doi: 10.1111/j.1530-0277.1995.tb01601.x. [DOI] [PubMed] [Google Scholar]
- 34.Xin Y, Lasker JM, Lieber CS. Serum carbohydrate-deficient transferrin: Mechanism of increase after chronic alcohol intake. Hepatology. 1995;22:1462–1468. [PubMed] [Google Scholar]
- 35.Stibler H., Borg S. Glycoprotein glycosyltransferase activities in serum in alcohol-abusing patients and healthy controls. Scand. J. Clin. Lab. Invest. 1991;51:43–51. doi: 10.3109/00365519109091621. [DOI] [PubMed] [Google Scholar]
- 36.Murawaki Y., Sugisaki H., Yuasa I., Kawasaki H. Serum carbohydrate-deficient transferrin in patients with nonalcoholic liver disease and with hepatocellular carcinoma. Clin. Chim. Acta. 1997;259:97–108. doi: 10.1016/S0009-8981(96)06473-X. [DOI] [PubMed] [Google Scholar]
- 37.Stauber R.E., Pesserl I., Wollman H. Carbohydrate-deficient transferrin in pre- and post-menopausal women. Alcohol Clin. Exp. Res. 1995;19:43A–43A. [Google Scholar]
- 38.Lesch O.M., Walter H., Antal J., Heggli D.E., Vovacz A., Leitner A., Neumeister A., Stumpf I., Sundrehagen E., Kasper S. Carbohydrate-deficient transferrin as a marker of alcohol intake: A study with healthy subjects. Alcohol Alcohol. 1996;31:265–271. doi: 10.1093/oxfordjournals.alcalc.a008146. [DOI] [PubMed] [Google Scholar]
- 39.Salmela K.S., Laitinen K., Nyström M., Salaspuro M. Carbohydrate-deficient transferrin during 3 weeks heavy alcohol consumption. Alcohol Clin. Exp. Res. 1994;18:228–230. doi: 10.1111/j.1530-0277.1994.tb00005.x. [DOI] [PubMed] [Google Scholar]
- 40.Fagerberg B., Agewall S., Urbanavicius V., Attvall S., Lundberg P.A., Lindstedt G. Carbohydrate-deficient transferrin is associated with insulin sensitivity in hypertensive men. J. Clin. Endocrinol. Metab. 1994;79:712–715. doi: 10.1210/jc.79.3.712. [DOI] [PubMed] [Google Scholar]
- 41.Yki-Järvinen H., Nikkila E.A. Ethanol decreases glucose utilization in healthy man. J. Clin. Endocrinol. Metab. 1985;6:941–945. doi: 10.1210/jcem-61-5-941. [DOI] [PubMed] [Google Scholar]
- 42.Kuvshinoff B.W., Brodish R.J., McFadden D.W., Fischer J.E. Serum transferrin as a prognostic indicator of spontaneous closure and mortality in gastrointestinal cutaneous fistula. Ann. Surg. 1993;217:615–622. doi: 10.1097/00000658-199306000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Skjöldebrand S.L., Brundin J., Carlström A., Schoultz B., Carlström K. Serum levels of estrogens and of five “steroid sensitive” proteins in early normal pregnancy. Acta. Endocrinologica. 1988;118:239–244. doi: 10.1530/acta.0.1180239. [DOI] [PubMed] [Google Scholar]
- 44.Anton F., Moak D.H. Carbohydrate-deficient transferrin and γ-glutamyl transferase as markers of heavy alcohol consumption: gender differences. Alcohol Clin. Exp. Res. 1994;18:747–754. doi: 10.1111/j.1530-0277.1994.tb00941.x. [DOI] [PubMed] [Google Scholar]
- 45.Stauber R.E., Jauk B., Fickert P., Häusler M. Increased carbohydrate-deficient transferrin during pregnancy: Relation to sex hormones. Alcohol Alcohol. 1996;31:389–392. doi: 10.1093/oxfordjournals.alcalc.a008167. [DOI] [PubMed] [Google Scholar]
- 46.Sillanaukee P., Alho H., Strid N., Jousilahti P., Vartiainen E, Olsson U, Sillanaukee P. Effect of hormone balance on carbohydrate-deficient transferrin and gamma glutamyl transferase in female social drinkers. Alcohol Clin Exp Res. 2000;24:1505–1509. doi: 10.1111/j.1530-0277.2000.tb04568.x. [DOI] [PubMed] [Google Scholar]
- 47.Stauber R.E., Vollman H, Pesserl I, Jauk B, Lipp R, Halwachs G, Wilders- Truschning M. Carbohydrate-deficient transferrin in healthy women: Relation to estrogens and iron status. Alcohol Clin Exp Res. 1996;20:1114–1117. doi: 10.1111/j.1530-0277.1996.tb01955.x. [DOI] [PubMed] [Google Scholar]
- 48.Leusink G.L., Smeets-Goevaers C.G., Breed S.A., Keyzer J.J., Pelt J. Carbohydrate-deficient transferrin in relation to the menopausal status in women. Alcohol Clin. Exp. Res. 2000;24:172–175. doi: 10.1111/j.1530-0277.2000.tb04587.x. [DOI] [PubMed] [Google Scholar]
- 49.DeJong G., vanNoort W.L., Feelders R.A., deJeu-Jaspars C.M.H., vanEijk H.G. Adaptation of transferrin protein and glycan synthesis. Clin. Chim. Acta. 1992;212:27–45. doi: 10.1016/0009-8981(92)90135-D. [DOI] [PubMed] [Google Scholar]
- 50.Cesarini L., Mandelli C., Fraquelli M., Velio P., Barisani D., Bianchi P.A., Conte D. Prevalence and degree of hepatic siderosis in 58 chronic alcohol abusers. Alcologia. 1991;3:129–132. [Google Scholar]
- 51.Duane P., Raja K.B., Simpson R.J., Peters T.J. Intestinal iron absorption in chronic alcoholics. Alcohol Alcohol. 1992;27:539–544. [PubMed] [Google Scholar]
- 52.Charlton R.W., Jacobs P., Steftel H., Bothwell T.H. Effect of alcohol on iron absorption. Br. Med. J. 1964;2:1427–1429. doi: 10.1136/bmj.2.5422.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.DeFeo T.M., Fargion S., Duca L., Mattioli M., Cappelini M.D., Sampietro M., Cesana B.M., Fiorelli G. Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron. Hepatol. 1999;29:658–663. doi: 10.1002/hep.510290326. [DOI] [PubMed] [Google Scholar]
- 54.Jensen P.D., Peterslund N.A., Poulsen J.H., Jensen F.T., Christensen T., Ellegaard J. The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin. Br. J. Haematol. 1994;88:56–63. doi: 10.1111/j.1365-2141.1994.tb04977.x. [DOI] [PubMed] [Google Scholar]
- 55.Arndt T. Carbohydrate-deficient-transferrin as a marker of chronic alcohol abuse: a critical review of preanalysis, analysis and interpretation. Clin. Chem. 2001;47:13–27. [PubMed] [Google Scholar]
- 56.Regoeczi E., Chindemi P.A., Debanne M.T. Transferrin glycans: a possible link between alcoholism and hepatic siderosis. Alcoholism. 1984;8:287–292. doi: 10.1111/j.1530-0277.1984.tb05513.x. [DOI] [PubMed] [Google Scholar]
- 57.Stibler H., Sydow S., Borg S. Quantitative estimation of abnormal microheterogeneity of serum transferrin in alcoholics. Biochem. Behav. 1980;13(Suppl 1):47–51. doi: 10.1016/s0091-3057(80)80008-6. [DOI] [PubMed] [Google Scholar]
- 58.Hackler R., Arndt T., Kleine T.O., Gressner A.M. Effect of separation conditions on automated isoelectric focusing of carbohydrate-deficient transferrin and other human isotransferrins using the PhastSystem. Anal. Biochem. 1995;230:281–289. doi: 10.1006/abio.1995.1475. [DOI] [PubMed] [Google Scholar]
- 59.Kilar F., Hjerten S. Fast and high resolution analysis of human serum transferrin by high performance isoelectric focusing in capillaries. Electrophoresis. 1989;10:23–29. doi: 10.1002/elps.1150100107. [DOI] [PubMed] [Google Scholar]
- 60.Tagliaro F., Crivellente F., Manetto G., Puppi I., Deyl Z., Marigo M. Optimized determination of carbohydrate-deficient transferrin isoforms in serum by capillary zone electrophoresis. Electrophoresis. 1998;19:3033–3039. doi: 10.1002/elps.1150191640. [DOI] [PubMed] [Google Scholar]
- 61.Inoue T., Yamauchi M., Ohkawa K. Structural studies on sugar chains of carbohydrate-deficient transferrin from patients with alcoholic liver disease using lectin affinity electrophoresis. Electrophoresis. 1999;30(1):13–26. doi: 10.1002/(SICI)1522-2683(19990301)20:3<452::AID-ELPS452>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
- 63.Das S.K., Nayak P., Vasudevan D.M. Biochemical markers for alcohol consumption. Ind. J. Clin. Biochem. 2003;18(2):111–118. doi: 10.1007/BF02867376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64.Arndt T., Behnken L., Martens B., Hackler R. Evaluation of the cut-off for serum carbohydrate-deficient transferrin as a marker of chronic alcohol abuse determined by the ChronAlco I.D.TM-Assay. J. Lab. Med. 1999;23:507–510. [Google Scholar]
- 65.Stibler H., Borg S., Joustra M. Micro anion exchange chromatography of carbohydrate-deficient transferrin in serum in relation to alcohol consumption. Alcohol Clin. Exp. Res. 1986;10:535–544. doi: 10.1111/j.1530-0277.1986.tb05138.x. [DOI] [PubMed] [Google Scholar]
- 66.Stibler H., Jaeken J. Carbohydrate deficient transferrin in a new systemic hereditary syndrome. Arch. Dis. Child. 1990;65:107–111. doi: 10.1136/adc.65.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67.Stibler H., Jaeken J., Kristiansson B. Biochemical characteristics and diagnosis of the carbohydrate-deficient glycoprotein syndrome. Acta. Paediatr. Scand. 1991;375:21–31. doi: 10.1111/j.1651-2227.1991.tb12025.x. [DOI] [PubMed] [Google Scholar]
- 68.Wada Y., Nishikawa A., Okamoto N., Inui K., Tsukamoto H., Okada S., Taniguchi N. Structure of serum transferrin in carbohydrate-deficient glycoprotein syndrome. Biochem. Biophys. Res. Commun. 1992;189:832–836. doi: 10.1016/0006-291X(92)92278-6. [DOI] [PubMed] [Google Scholar]
- 69.Hagberg B.A., Blennow G., Kristiansson B., Stibler H. Carbohydrate-deficient glycoprotein syndromes: Peculiar group of new disorders. Pediatr. Neurol. 1993;9:255–262. doi: 10.1016/0887-8994(93)90060-P. [DOI] [PubMed] [Google Scholar]
- 70.Yamashita K., Ideo H., Ohkura T., Fukushima K., Yuasa I., Ohno K., Takeshita K. Sugar chains of serum transferrin from patients with carbohydrate-deficient glycoprotein syndrome. J. Biol. Chem. 1993;268:5783–5789. [PubMed] [Google Scholar]
- 71.Giblett E. The plasma transferrins. Prog. Med. Genet. 1962;2:34–63. [Google Scholar]
- 72.Bell H., Tallaksen C., Sjaheim T., Weberg R., Raknerud N., Orjasaeter H., Try K., Haug E. Serum carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with chronic liver diseases. Alcohol Clin. Exp. Res. 1993;17:246–252. doi: 10.1111/j.1530-0277.1993.tb00757.x. [DOI] [PubMed] [Google Scholar]
- 73.DeFeo T.M., Duca L., Colucci P., Meloni A.R., Fargion S., Fiorelli G. Is carbohydrate-deficient transferrin (CDT) a useful marker of high alcohol consumption in cirrhosis? Gastroenterology. 1997;112(Suppl 4):A1253–A1253. [Google Scholar]
- 74.Meregalli M., Giacomini V., Lino S., Marchetti L., DeFeo T.M., Cappellini M.D., Fiorelli G. Carbohydrate-deficient transferrin in alcohol and non-alcohol abusers with liver disease. Alcohol Clin. Exp. Res. 1995;19:1525–1527. doi: 10.1111/j.1530-0277.1995.tb01018.x. [DOI] [PubMed] [Google Scholar]
- 75.Bean P., Sutphin M.S., Liu Y.S., Anton R., Reynolds T.B., Shoenfeld Y., Peter J.B. Carbohydrate-deficient transferrin and false-positive results for alcohol abuse in primary biliary cirrhosis: Differential diagnostic by detection of mitochondrial autoantibodies. Clin. Chem. 1995;41:858–861. [PubMed] [Google Scholar]
