Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the AFPgene. The AFP gene is located on the q arm of chromosome 4 (4q25).
AFP is the most abundant plasma protein found in the human fetus. Plasma levels decrease rapidly after birth but begin decreasing prenatally starting at the end of the first trimester. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adult humans is unknown; however, in rodents it binds estradiol to prevent the transport of this hormone across the placenta to the fetus. The main function of this is to prevent the virilization of female fetuses. As human AFP does not bind estrogen, its function in humans is less clear.
The rodent AFP system can be overridden with massive injections of estrogen, which overwhelm the AFP system and will masculinize the fetus. The masculinizing effect of estrogens may seem counter-intuitive since estrogens are critical for the proper development of female secondary characteristics during puberty. However, this is not the case prenatally. Gonadal hormones from the testes, such as testosterone and antimullerian hormone are required to cause development of a phenotypic male. Without these hormones the fetus will develop into a phenotypic female even if genetically XY. Interestingly, the conversion of testosterone into estradiol by aromatase in many tissues may be an important step in masculinization of that tissue. Masculinization of the brain is thought to occur both by conversion of testosterone into estradiol by aromatase, but also by de novo synthesis of estrogens within the brain. Thus, AFP may protect the fetus from maternal estradiol that would otherwise have a masculinizing effect on the fetus, but its exact role is still controversial.
In pregnant women, fetal AFP levels can be monitored in urine. Since AFP is quickly cleared from the mother's serum via her kidneys, maternal urine AFP correlates with fetal serum levels, although the maternal urine level is much lower than the fetal serum level. AFP levels rise until about week 32.
The normal range of AFP for adults and children is variously reported as under 50, under 10, and under 5 ng/mL. At birth, normal infants have AFP levels 4 or more orders of magnitude above this normal range, that decreases to a normal range over the first year of life.
During this time, the normal range of AFP levels spans approximately 2 orders of magnitude. Correct evaluation of abnormal AFP levels in infants must take into account these normal patterns.
Very high AFP levels may be subject to hooking (see Tumor marker), which results in the level being reported significantly lower than the actual concentration. This is important for analysis of a series of AFP tumor marker tests, e.g. in the context of post-treatment early surveillance of cancer survivors, where the rate of decrease of AFP has diagnostic value.
Measurement of AFP is generally used in two clinical contexts. First, it is measured in pregnant women through the analysis of maternal blood or amniotic fluid as a screening test for certain developmental abnormalities. Second, serum AFP level is elevated in people with certain tumors, and so it is used as a biomarker to follow these diseases. Some of these diseases are listed below:
developmental birth defects associated with elevated AFP
^Harding CF (2004). "Hormonal modulation of singing: hormonal modulation of the songbird brain and singing behavior.". Annals of the New York Academy of Sciences. 1016: 524–39. PMID15313793. doi:10.1196/annals.1298.030.
^Sizaret P, Martel N, Tuyns A, Reynaud S (February 1977). "Mean alpha-fetoprotein values of 1,333 males over 15 years by age groups". Digestion. 15 (2): 97–103. PMID65304. doi:10.1159/000197990.
^Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U (1998). "Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age". Pediatr Hematol Oncol. 15 (2): 135–42. PMID9592840. doi:10.3109/08880019809167228.
^Ohama K, Nagase H, Ogino K, Tsuchida K, Tanaka M, Kubo M, Horita S, Kawakami K, Ohmori M (October 1997). "Alpha-fetoprotein (AFP) levels in normal children". Eur J Pediatr Surg. 7 (5): 267–9. PMID9402482. doi:10.1055/s-2008-1071168.
^ abcLee PI, Chang MH, Chen DS, Lee CY (January 1989). "Serum alpha-fetoprotein levels in normal infants: a reappraisal of regression analysis and sex difference". J. Pediatr. Gastroenterol. Nutr. 8 (1): 19–25. PMID2471821. doi:10.1097/00005176-198901000-00005.
^Bader D, Riskin A, Vafsi O, Tamir A, Peskin B, Israel N, Merksamer R, Dar H, David M (November 2004). "Alpha-fetoprotein in the early neonatal period--a large study and review of the literature". Clin. Chim. Acta. 349 (1-2): 15–23. PMID15469851. doi:10.1016/j.cccn.2004.06.020.
^Wu JT, Roan Y, Knight JA (1985). "Serum levels of AFP in normal infants: their clinical and physiological significance". In Mizejewski GJ, Porter I. Alfa-Fetoprotein and Congenital Disorders. New York: Academic Press. pp. 111–122.
^Szabó M, Veress L, Münnich A, Papp Z (September 1990). "[Alpha fetoprotein concentration in the amniotic fluid in normal pregnancy and in pregnancy complicated by fetal anomaly]". Orv Hetil (in Hungarian). 131 (39): 2139–42. PMID1699194.
^Ertle, JM; Heider, D; Wichert, M; Keller, B; Kueper, R; Hilgard, P; Gerken, G; Schlaak, JF (2013). "A combination of α-fetoprotein and des-γ-carboxy prothrombin is superior in detection of hepatocellular carcinoma.". Digestion. 87 (2): 121–31. PMID23406785. doi:10.1159/000346080.
Yachnin S, Hsu R, Heinrikson RL, Miller JB (1977). "Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis". Biochim. Biophys. Acta. 493 (2): 418–28. PMID70228. doi:10.1016/0005-2795(77)90198-2.
Aoyagi Y, Ikenaka T, Ichida F (1977). "Comparative chemical structures of human alpha-fetoproteins from fetal serum and from ascites fluid of a patient with hepatoma". Cancer Res. 37 (10): 3663–7. PMID71198.
Aoyagi Y, Ikenaka T, Ichida F (1978). "Copper(II)-binding ability of human alpha-fetoprotein". Cancer Res. 38 (10): 3483–6. PMID80265.
Aoyagi Y, Ikenaka T, Ichida F (1979). "alpha-Fetoprotein as a carrier protein in plasma and its bilirubin-binding ability". Cancer Res. 39 (9): 3571–4. PMID89900.
Torres JM, Anel A, Uriel J (1992). "Alpha-fetoprotein-mediated uptake of fatty acids by human T lymphocytes". J. Cell. Physiol. 150 (3): 456–62. PMID1371512. doi:10.1002/jcp.1041500305.
Greenberg F, Faucett A, Rose E, et al. (1992). "Congenital deficiency of alpha-fetoprotein". Am. J. Obstet. Gynecol. 167 (2): 509–11. PMID1379776.
Bansal V, Kumari K, Dixit A, Sahib MK (1991). "Interaction of human alpha fetoprotein with bilirubin". Indian J. Exp. Biol. 28 (7): 697–8. PMID1703124.
Pucci P, Siciliano R, Malorni A, et al. (1991). "Human alpha-fetoprotein primary structure: a mass spectrometric study". Biochemistry. 30 (20): 5061–6. PMID1709810. doi:10.1021/bi00234a032.
Gibbs PE, Zielinski R, Boyd C, Dugaiczyk A (1987). "Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene". Biochemistry. 26 (5): 1332–43. PMID2436661. doi:10.1021/bi00379a020.
Sakai M, Morinaga T, Urano Y, et al. (1985). "The human alpha-fetoprotein gene. Sequence organization and the 5' flanking region". J. Biol. Chem. 260 (8): 5055–60. PMID2580830.
Ruoslahti E, Pihko H, Vaheri A, et al. (1975). "Alpha fetoprotein: structure and expression in man and inbred mouse strains under normal conditions and liver injury". Johns Hopkins Med. J. Suppl. 3: 249–55. PMID4138095.