Advertisement

Human Genetics

, Volume 72, Issue 4, pp 281–293 | Cite as

Ethnic variation in vitamin D-binding protein (GC): a review of isoelectric focusing studies in human populations

  • M. I. Kamboh
  • R. E. Ferrell
Review Articles

Summary

Since the discovery in 1977 that the GC1 gene could be resolved into two common subcomponents on an isoelectric focusing (IEF) gel, a large number of ethnic groups have been screened to analyze the extent of genetic variation in human populations. Using the IEF technique, approximately 50,000 individuals from 160 different populations have been tested for the GC polymorphism. A marked variation in common GC suballele frequencies in different geographic areas seems to correlate with skin pigmentation and intensity of sun light. Pigmented (black) and keratinized (yellowish) skin type populations have a relatively high frequency of the GC*IF allele as compared to white skin populations. By comparison non-pigmented and non-keratinized white skin populations are generally characterized by having the maximum values of the GC*IS allele. The anthropologic significance of the GC locus has been enhanced further by detecting additional unique GC variants which provide useful information about evolutionary links between different populations. However, the presence of some electrophoretically identical unique variants in genetically and geographically distinct populations demand further investigation of these allelic variants to shed more light on their origins.

Keywords

Human Population Unique Variant Distinct Population Ethnic Variation Marked Variation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ayala FJ (1982) Genetic variation in natural populations. Problems of electrophoretically cryptic alleles. Proc Natl Acad Sci USA 79:550–554Google Scholar
  2. Bellwood P (1978) Man's conquest of the Pacific. Collins, Auckland Sydney LondonGoogle Scholar
  3. Bouillon R, van Baelen H, Rombauts W, DeMoor P (1976) The purification and characterization of the human serum binding protein for the 25-hydroxycholecalciferol (transcalciferin) identity with group-specific component. Eur J Biochem 66:285–291Google Scholar
  4. Cleve H (1973) The variants of the group-specific component. A review of their distribution in human populations. Isr J Med Sci 9:1133–1146Google Scholar
  5. Cleve H, Dencker H (1966) Quantitative variations of the group specific component (Gc) and of barium-α2-glycoprotein of human serum in health and disease. In: Peters H (ed) Protides of the biological fluids, vol 14. Elsevier, Amsterdam, pp 379–384Google Scholar
  6. Cleve H, Patutschnick W (1977) The vitamin D binding of the common and rare variants of the group specific component (Gc). Hum Genet 38:289–296Google Scholar
  7. Cleve H, Patutschnick W (1979) Neuraminidase treatment reveals sialic acid differences in certain genetic variants of the Gc system (vitamin-D-binding protein). Hum Genet 47:193–198Google Scholar
  8. Cleve H, Kirk RL, Bearn AG, Schacht LE, Kleinman H, Horsfail WR (1963) Two genetic variants of the group-specific component of human serum. Gc Chippewa and Gc Aborigine. Am J Hum Genet 15:368–379Google Scholar
  9. Cleve H, Krupe M, Ensgraber A (1966) Zur Vererbung der Gc-Variante GcZ. Bericht über eine weitere Familie. Humangenetik 3:46–49Google Scholar
  10. Cleve H, Patutschnick W, Nevo S, Wendt GG (1978) Genetic studies of the Gc subtypes. Hum Genet 44:117–122Google Scholar
  11. Cleve H, Constans J, Berg S, Hoste B, Ishimoto G, Matsumoto M, Spees EK, Weber W (1981) GC revisited: six further Gc-phenotypes delineated by isoelectric focusing and by polyacrylamide gel electrophoresis. Hum Genet 57:312–316Google Scholar
  12. Constans J, Viau M (1977) Group-specific component: evidence for two subtypes of the Gc gene. Science 198:1070–1071Google Scholar
  13. Constans J, Salzano FM (1980) Gc and transferrin isoelectric focusing subtypes among Brazilian Indians. J Hum Evol 9:489–494Google Scholar
  14. Constans J, Viau M, Cleve H, Jaeger G, Quilici JC, Palisson MJ (1978a) Analysis of the Gc polymorphism in human populations by isoelectric focusing on polyacrylamide gels. Demonstration of subtypes of the Gc allele and of additional Gc variants. Hum Genet 41:53–60Google Scholar
  15. Constans J, Viau M, Pison G, Langaney A (1978b) Gc subtypes demonstrated by isoelectric focusing: further data and description of new variants among an African sample (Fula) from Senegal. Jinrui Idengaku Zasshi 23:111–117Google Scholar
  16. Constans J, Viau M, Moatti JP, Clavere JL (1979a) Serum vitamin D binding protein and Gc polymorphism. In: Vitamin D, basic research and its clinical application. de Gruyter, Berlin New York, pp 153–156Google Scholar
  17. Constans J, Cleve H, Bennet A, Bouillon R, Cox DW, Daiger SP, Ehnol C, Fujiki N, Johnson AM, Kirk RL, Kuhnl P, Martin W, Matsumoto M, Mayr WR, Miyake K, Miyazaki T, Omoto K, Porck HJ, Seger J, Thymann M, Tills D, Toyomasur M, Van Baeten H, Vavrusa B, Viau M (1979b) Group-specific component. Report on the first international workshop. Hum Genet 48:143–149Google Scholar
  18. Constans J, Lefevre-Witier Ph, Richard P, Jaeger G (1980a) Gc (vitamin D binding protein) subtype polymorphism and variants distribution among Saharan, Middle East and African populations. Am J Phys Anthropol 52:435–441Google Scholar
  19. Constans J, Viau M, Bouissou C (1980b) Affinity differences for the 25-OH-D3 associated with the genetic heterogeneity of the vitamin D-binding protein. FEBS Lett 111:107–111Google Scholar
  20. Constans J, Oksman F, Viau M (1981a) Binding of the apo and holo forms of the serum vitamin D-binding protein to human lymphocyte and membrane by direct immunofluorescence. Immunol Lett 3:159–162Google Scholar
  21. Constans J, Viau M, Jaeger G, Palisson MJ (1981b) Gc, Tf, Hp subtype and alpha-1-antitrypsin polymorphism in a pygmy Bi-Aka sample. Phenotype association between TfD1 and Gc1A1 (GcAb) variants. Hum Hered 31:129–137Google Scholar
  22. Constans J, Arlet Ph, Viau M, Bouiossu C (1983a) Unusual sialilation of the serum DBP associated with the Gc 1 allele in alcoholic cirrhosis of the liver. Clin Chim Acta 130:219–230Google Scholar
  23. Constans J, Cleve H, Dykes D, Fischer M, Kirk RL, Papiha SS, Scheffran W, Scherz R, Thymann M, Weber W (1983b) Isoelectric focusing in 3M urea as additional method for identification of genetic variants. Hum Genet 65:176–180Google Scholar
  24. Constans J, Hazout S, Garruto RM, Gajdusek DC, Spees EK (1985) Population distribution of the human vitamin D binding protein: anthropological considerations. Am J Phys Anthropol 68:107–122Google Scholar
  25. Cooper DW (1978) Inherited variation in plasma proteins. In: Brock DJH, Mayo O (eds) The biochemical genetics of man, 2nd edn. Academic Press, New York London, pp 271–324Google Scholar
  26. Coue M, Constans J, Viau M, Olomucki A (1983) The effect of serum vitamin D-binding protein on polymerization and depolymerization of actin is similar to the effect of profilin on actin. Biochim Biophys Acta 759:137–145Google Scholar
  27. Cox DW, Simpson NE, Jantti R (1978) Group-specific component, alpha-1-antitrypsin and esterase D in Canadian Eskimos. Hum Hered 28:341–350Google Scholar
  28. Daiger SP, Cavalli-Sforza LL (1977) Detection of genetic variation with radioactive ligands 11. Genetic variants of vitamin D-labelled group-specific component (Gc) proteins. Am J Hum Genet 29:593–604Google Scholar
  29. Daiger SP, Schanfield MS, Cavalli-Sforza LL (1975) Group-specific component (Gc) proteins bind vitamin D and 25-hydroxy vitamin D. Proc Natl Acad Sci USA 72:2076–2080Google Scholar
  30. Dykes DD, Polesky HF (1982) Gc 1C12: a new Gc variant. Hum Hered 32:136–138Google Scholar
  31. Dykes DD, Polesky HF (1984) Review of isoelectric focusing for Gc, PGM1, Tf and Pi subtypes — population distributions. CRC Crit Rev Clin Lab Sci 20:115–151Google Scholar
  32. Dykes DD, Crawford MH, Polesky HF (1983) Population distribution in North and Central America of PGM1 and Gc subtypes as determined by isoelectric focusing (IEF). Am J Phys Anthropol 62:137–146Google Scholar
  33. Fawcett JS (1968) Isoelectric fraction of proteins on polyacrylamide gels. FEBS Lett 1:81–82Google Scholar
  34. Garber RA, Delapointe L, Morris JW (1983) PGM1 and GC subtype gene frequencies in a California Hispanic population. Am J Hum Genet 35:773–776Google Scholar
  35. Goedde HW, Rothammer F, Benkmann HG, Bogdenski P (1985) Genetic studies in Atacameno Indians: serum protein and red cell enzyme polymorphisms. Ann Hum Biol 12:251–259Google Scholar
  36. Haddad JG Jr, Walgate J (1976) 25-Hydroxy vitamin D transport in human plasma. Isolation and partial characterization of calcifodiol-binding protein. J Biol Chem 251:4803–4809Google Scholar
  37. Harris H (1980) The principles of human biochemical genetics. North Holland Biomedical Press/Elsevier, AmsterdamGoogle Scholar
  38. Hirschfeld J (1959) Immunoelectrophoretic demonstration of qualitative differences in human sera and their relation to the haptoglobins. Acta Pathol Microbiol Scand 47:160–168Google Scholar
  39. Hirschfeld J, Jonsson B, Rasmusan M (1960) Inheritance of a new group-specific system demonstrated in normal human sera by means of an immunoelectrophoretic technique. Nature 185:931–932Google Scholar
  40. Holick MF, MacLaughlin JA, Clark MB, Holick SA, Polts JT (1980) Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 210:203–205Google Scholar
  41. Hoste B (1979) Group-specific component (Gc) and transferrin (Tf) subtypes ascertained by isoelectric focusing: a simple nonimmunological staining procedure for Gc. Hum Genet 50:75–79Google Scholar
  42. Imawari M, Goodman DS (1977) Immunological and immunoassay studies of the binding protein for vitamin D and its metabolites in human serum. J Clin Invest 59:432–442Google Scholar
  43. Ishimoto G, Kuwata M, Nakajima H (1979) Group-specific component (Gc) polymorphism in Japanese. An analysis by isoelectric focusing on polyacrylamide gels. Jinrui Idengaku Zasshi 24:75–83Google Scholar
  44. Johnson AM, Cleve H, Alper CA (1975) Variants of the group-specific component system as demonstrated by immunofixation electrophoresis. Report of a new variant, Gc Boston (GcB). Am J Hum Genet 27:728–736Google Scholar
  45. Kamboh MI, Kirk RL (1983) Distribution of transferrin (Tf) subtypes in Asian, Pacific and Australian aboriginal populations. Evidence for the existence of a new subtype TfC6. Hum Hered 33:237–243Google Scholar
  46. Kamboh MI, Kirk RL, Clark P (1983) Alpha-1-antitrypsin (PI) types in Asian, Pacific and aboriginal Australian populations. Dis Markers 1:33–42Google Scholar
  47. Kamboh MI, Ranford PR, Kirk RL (1984) Population genetics of the vitamin D-binding protein (GC) subtypes in the Asian, Pacific area: description of new alleles at the GC locus. Hum Genet 67:378–384Google Scholar
  48. Karlsson S, Skaftadottir I, Arnason A, Thordarson G, Jensson O (1983a) Gc subtypes in Icelanders. Hum Hered 33:5–8Google Scholar
  49. Karlsson S, Skaftadottir I, Arnason A, MacKintosh P, Jensson O (1983b) Gc subtypes in Northern Indians. Hum Hered 33:199–200Google Scholar
  50. Kawai N, Matsui K, Shibata K (1983) Vitamin D binding protein (Gc) concentration difference of vitamin D binding protein subtypes among normal and liver cirrhosis (Abstract). Jinrui Idengaku Zasshi 28:119Google Scholar
  51. Kawakami M, Goodman DS (1981) Effect of protein modification procedures on the interaction between 25-hydroxy vitamin D and human plasma binding protein for vitamin D and its metabolites. Biochemistry 20:5881–5887Google Scholar
  52. Kirk RL (1980) Language, genes and people in the Pacific. In: Eriksson AW (ed) Population structure and genetic disorders. Academic Press, New York London, pp 113–137Google Scholar
  53. Kirk RL (1982a) Microevolution and migration in the Pacific. In: Human genetics, part A: The unfolding genome. Liss, New York, pp 215–225Google Scholar
  54. Kirk RL (1982b) Linguistic, ecological and genetic differentiation in New Guinea and the Western Pacific. In: Crawford MH, Mielke JH (eds) Current developments in anthropological genetics 2. Ecology and population structure. Plenum Press, New York, pp 229–253Google Scholar
  55. Kirk RL, Cleve H, Bearn AG (1963) The distribution of the Gc types in sera from Australian aborigines. Am J Phys Anthropol 21:215–223Google Scholar
  56. Kitchin FD (1965) Demonstration of the inherited serum group-specific component by acrylamide electrophoresis. Proc Soc Exp Biol Med 119:1153–1155Google Scholar
  57. Kueppers F, Harpel B (1979) Group-specific component (Gc) ‘subtypes’ of Gc1 by isoelectric focusing in US Blacks and Whites. Hum Hered 29:242–249Google Scholar
  58. Kuhnl P, Spielmann W, Loa M (1978) An improved method for the identification of Gc1 subtypes (group-specific component) by isoelectric focusing. Vox Sang 35:401–404Google Scholar
  59. Kuwata M, Ishimoto G, Nakajima H (1978) Group-specific component (Gc) polymorphism in Japanese: an investigation on the phenotypic distribution with regard to the GcJ allele. Jinrui Idengaku Zasshi 23:127–132Google Scholar
  60. Kwok KYY, Lewis WHP (1981) Group-specific component (Gc) subtypes in the Chinese population of Hong Kong. Hum Genet 59:72–74Google Scholar
  61. Lefranc MP, Chibani J, Helal AN, Boukef K, Seger J, Lefranc G (1981) Human transferrin (Tf) and group-specific component (Gc) subtypes in Tunisia. Hum Genet 59:60–63Google Scholar
  62. Litwiak R, Henningsen K (1977) Elektrophoretische und genetische Untersuchungen von 2 varianten Gc Phänotypen. Ärztl Lab 23:491–495Google Scholar
  63. Loomis WF (1967) Skin-pigment regulation of vitamin-D biosynthesis in man. Science 157:501–506Google Scholar
  64. Matsumoto M, Matsui K, Ishida H, Ohkura K, Teng Y-S (1980) The distribution of GC subtypes among the mongoloid populations. Am J Phys Anthropol 53:505–508Google Scholar
  65. Mourant AE, Tills D, Domaniewski-Sobczak K (1976) Sunshine and the geographical distribution of the alleles of the Gc system of plasma proteins. Hum Genet 33:307–314Google Scholar
  66. Nakasono I, Iwasaki M, Ogata M, Yoshida C, Yoshitake T, Narita K, Suyama H, Tomohiro Y (1983) A new single band variant of the Gc subtypes determined by isoelectric focusing. Hum Genet 64:184–185Google Scholar
  67. Nakasono I, Iwasaki M, Ogata M, Yoshitake T, Narita K, Kubo S, Suyama H, Tanoue Y (1985) A new hereditary single band variant of the Gc system. Hum Genet 70:84–85Google Scholar
  68. Nevo S, Cleve H (1983) Gc subtypes in the Middle East: report on an Arab Moslem population from Isreal. Am J Phys Anthropol 60:49–52Google Scholar
  69. Nicholls C, Mulley JC (1982) Distribution of the Gc (group-specific component) subtypes in cord blood and blood donors. Aust J Exp Biol Med Sci 60:427–431Google Scholar
  70. Omoto K, Miyake K (1978) The distribution of the group-specific component (Gc) subtypes in Japanese. Jinrui Idengaku Zasshi 23:119–125Google Scholar
  71. Omoto K, Misawa S, Harada S, Sumpaico JS, Medaolo PM, Ognuki H (1978) Population genetic studies of the Philippine Negritos. I. A pilot survey of red cell enzyme and serum protein groups. Am J Hum Genet 30:190–201Google Scholar
  72. Papiha SS, Roberts DF, White I, Chahal SMS, Asefi JA (1982a) Population genetics of the group-specific component (Gc) and phosphoglucomutase (PGM1) studied by isoelectric focusing. Am J Phys Anthropol 59:1–7Google Scholar
  73. Papiha SS, Seyedna Y, Sunderland E (1982b) Phosphoglucomutase (PGM) and group-specific component (Gc), isoelectric focusing subtypes among Zoroastrians of Iran. Ann Hum Biol 9:571–574Google Scholar
  74. Papiha SS, White I, Roberts DF (1983) Some genetic implications of isoelectric focusing of human red cell protein group-specific component (Gc). Genetic diversity in the populations of Himachal Pradesh, India. Hum Genet 63:67–72Google Scholar
  75. Papiha SS, Constans J, White I, McGregor IA (1985) Group-specific component (GC) subtypes in Gambian and Transkerian populations: a description of new variant. Ann Hum Biol 12:17–26Google Scholar
  76. Petrucci R, Congedo P (1983) Genetic studies of Gc (vitamin D binding globulin) polymorphisms in the population of Latium (Italy). J Hum Evol 12:439–441Google Scholar
  77. Righetti PG, Drysdale JW (1976) Isoelectric focusing. In: Work TS, Work E (eds) Laboratory techniques in biochemistry and molecular biology, vol 5. North Holland/American Elsevier, Amsterdam New YorkGoogle Scholar
  78. Riley RF, Coleman MK (1968) Isoelectric fraction of proteins on a microscale in polyacrylamide gel and agarose matrices. J Lab Clin Med 72:714–720Google Scholar
  79. Salzano FM, Mohernweiser M, Gershowitz H, Neel JV, Mestriner MA, Simoes L, Constans J, DeMeloeFreitas MJ (1984) New studies on the Machushi Indians of Northern Brazil. Ann Hum Biol 11:337–350Google Scholar
  80. Salzano FM, Weiner JA, Franco MHLP, Mestriner MA, Simoes AL, Constans J, DeMeloeFreitas MJ (1985) Population structure and blood genetic of the Pacaas Novos Indians of Brazil. Ann Hum Biol 12:241–249Google Scholar
  81. Scheil HG, Driesel AJ, Rohrborn G (1980) Distribution of Gc subtypes in Western Germany (Düsseldorf region). Z Rechtsmed 84:95Google Scholar
  82. Serjeantson SW, Ryan DR, Thompson AR (1982) The colonization of the Pacific: the story according to human leukocyte antigens. Am J Hum Genet 34:904–918Google Scholar
  83. Serjeantson SW, Kirk RL, Ranford P, Beauchamp M (1983) HLA antigens and non-HLA chromosome 6 markers in Micronesian from Nauru. Tissue Antigens 22:49–58Google Scholar
  84. Shibata K (1983) Haptoglobin, group-specific component, transferrin and alpha-1-antitrypsin subtypes and new variants in Japanese. Jinrui Idengaku Zasshi 28:17–27Google Scholar
  85. Smithies O (1955) Zone electrophoresis in starch gels. Group variations in the serum proteins of normal human adults. Biochem J 61:629–641Google Scholar
  86. Speiser P, Pausch V, Cleve H (1972) A new rapid migrating variant in the Gc system, Gc Wien. Hum Genet 17:81–84Google Scholar
  87. Svasti J, Bowman BH (1978) Human group-specific component. Changes in electrophoretic mobility resulting from vitamin D binding and from neuraminidase digestion. J Biol Chem 253:4188–4194Google Scholar
  88. Svasti J, Kurosky A, Bennett A, Bowman BH (1979) Molecular basis for the three major forms of human serum vitamin D binding protein (group-specific component). Biochemistry 18:1611–1617Google Scholar
  89. Svensson H (1961) Isoelectric fractionation: analysis and characterization of ampholytes in natural pH gradients. I. The differential equation of solute concentrations at a steady state and its solution for simple cases. Acta Chem Scand 15:325–341Google Scholar
  90. Svensson H (1962) Isoelectric fractionation: analysis and characterization of ampholytes in natural pH gradients. III. Description of apparatus for electrolysis in columns stabilized by density gradients and direct determination of isoelectric points. Arch Biochem Biophys (Suppl) 1:131–132Google Scholar
  91. Svensson M, Hjalmarsson K (1981) Distribution of Gc subtypes by isoelectric focusing in Sweden. 9. International Faguny der Gesellschaft für Forensische Blutgruppen Kunder, p 559Google Scholar
  92. Tan SG, Gan YY, Asuan K, Abdullah F (1981) Gc subtyping in Malaysians and in Indonesians from North Sumatra. Hum Genet 59:75–76Google Scholar
  93. Thomas WC, Morgan HG, Conners TB, Haddock L, Bills CE, Hovord JE (1959) Studies of antiricketic activity in sera from patients with disorders of calcium metabolism and preliminary observations on the mode of transport of vitamin D in human sera. J Clin Invest 38:1078–1085Google Scholar
  94. Thymann M (1981) GC subtypes determined by agarose isoelectric focusing. Distribution in Denmark and application to paternity cases. Hum Hered 31:214–221Google Scholar
  95. Thymann M, Hjalmarsson K, Svensson M (1982) Five new Gc variants detected by isoelectric focusing in agarose gel. Hum Genet 60:340–343Google Scholar
  96. Thymann M, Hoste B, Scheffrahn W, Constans J, Cleve II (1985) Unusual sialilation of three different rare genetic variants of serum DBP: Gc1A17, Gc1A16 and Gc1A11. Hum Genet 69:224–227Google Scholar
  97. Van Baelen H, Bouillon R, DeMoor P (1980) Vitamin D-binding protein (Gc globulin) binds actin. J Biol Chem 255:2270–2272Google Scholar
  98. Vavrusa B, Cleve H (1974) Gc Opava: a variant of the group-specific component (Gc) system with an electrophoretic mobility intermediate between Gc1-1 and Gc2-2. Vox Sang 26:157–162Google Scholar
  99. Vesterberg O, Svensson H (1966) Isoelectric fractionation: analysis and characterization of ampholytes in natural pH gradients. IV. Further studies on the resolving power in connection with separation of myoglobulins. Acta Chem Scand 20:820–834Google Scholar
  100. Weidinger S, Cleve H, Schwarzfischer F, Patutschnick W (1981) The Gc system in paternity examinations, application of Gc subtyping by isoelectric focussing. In: Hummel K, Gerchow J (eds) Biomathematical evidence of paternity. Springer, Berlin Heidelberg New York, pp 113–121Google Scholar
  101. Yuasa I, Saneshige Y, Okamoto N, Ikawa S, Hikita T, Ikebuchi K, Inoue T, Okada K (1983a) Distribution of Hp, Tf, Gc and Pi polymorphisms in a Nepalese population. Hum Hered 33:302–306Google Scholar
  102. Yuasa I, Saneshige Y, Okamoto N, Inoue T, Okada K (1983b) Distribution of Hp, Tf, Gc and Pi polymorphisms in a Japanese population samples from Sanin District. J Anthrop Soc Nippon 91:395–400Google Scholar
  103. Yuasa I, Suenaga K, Gotoh Y, Ito K, Yokoyama N (1984) Group-specific component (Gc) in Western Japan: report of a new variant Gc IC35. Hum Hered 34:174–177Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • M. I. Kamboh
    • 1
  • R. E. Ferrell
    • 1
  1. 1.Department of Biostatistics, Human Genetics Program, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA

Personalised recommendations