Skip to main content
Log in

ACP1 and human adaptability 1. Association with common diseases: a case-control study

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Human red cell acid phosphatase (ACP1) is a polymorphic enzyme closely related to cytosolic low molecular weight acid phosphatases, a protein family broadly conserved among eukaryotes. Two different functions have been proposed for ACP1: flavin mononucleotide (FMN) phosphatase and phosphotyrosine phosphatase (PTPase). Given that genetic variants of ACP1 activity are common, the enzyme could have a role in regulating a large spectrum of cellular functions and, in turn, disease susceptibility. In the present paper we report a study of ACP1 genetic polymorphism in 1088 normal subjects and in 1267 subjects from the population of Rome admitted to hospital for a number of common diseases. All ACP1 parameters investigated show highly significant differences among samples, suggesting that the enzyme may have a significant role in some of the diseases considered. In particular, consistent associations of ACP1 with developmental disturbances and with hemolytic favism have been observed. In the majority of diseases showing association with ACP1, only one of the two ACP1 isoforms, f and s, is involved, supporting the hypothesis of a functional differentiation between the two enzymatic fractions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amante A, Gloria-Bottini F, Bottini E (1990) Intrauterine growth: association with acid phosphatase genetic polymorphism. J Perinat Med 18:275–282

    Google Scholar 

  • Ananthakrishnan R, Walter H (1972) Some notes on the geographical distribution of the human red cell acid phosphatase phenotypes. Humangenetik 15:177–181

    Google Scholar 

  • Boivin P, Galand C (1986) The human red cell acid phosphatase is a phosphotyrosine protein phosphatase which dephosphorylates the membrane protein band 3. Biochem Biophys Res Commun 134:557–564

    Google Scholar 

  • Bottini E, Modiano G (1964) Effect of oxidized glutathione on human red cell acid phosphatases. Biochem Biophys Res Commun 17:260–264

    Google Scholar 

  • Bottini E, Lucarelli P, Agostino R, Palmarino R, Businco L, Antognoni (1971a) Favism: association with erythrocyte acid phosphatase phenotype. Science 171:409–411

    Google Scholar 

  • Bottini E, Modiano G, Santolamazza C, Filippi G, Businco L (1971b) Studies of the “in vitro” effects of oxidized glutathione and acetylphenylhydrazine on acid phosphatases on human red blood cell. An experimental model for the investigation of hemolytic drug action at the molecular level. Clin Chim Acta 31:243–254

    Google Scholar 

  • Bottini E, Lucarelli P, Bastianon V, Gloria F (1972) Erythrocyte acid phosphatase polymorphism and haemolysis. J Med Genet 9:434–435

    Google Scholar 

  • Bottini E, Scacchi R, Gloria-Bottini F, Mortera J, Palmarino R, Carapella-De Luca E, Lapi AS, Nodari C (1976) Neonatal jaundice and erythrocyte-acid-phosphatase phenotype. Lancet 1:918

    Google Scholar 

  • Bottini E, Gloria-Bottini F, Lucarelli P, Polzonetti A, Santoro F, Varveri A (1979) Genetic polymorphisms and intrauterine development. Evidence of decreased heterozygosity in light-fordate human newborn babies. Experientia 35:1565–1566

    Google Scholar 

  • Bottini E, Lucarini N, Gerlini G, Finocchi G, Scire G, Gloria-Bottini F (1990) Enzyme polymorphism and clinical variability of diseases — study of acid phosphatase locus-1 (Acp1) in obese subjects. Hum Biol 62:403–411

    Google Scholar 

  • Camici G, Manao G, Cappugi G, Modesti A, Stefani M, Ramponi G (1989) The complete amino acid sequence of the low molecular weight cytosolic acid phosphatase. J Biol Chem 264:2560–2567

    Google Scholar 

  • Carapella E, Pascone R, Gori MG, Matteucci P, Gloria-Bottini F, Mortera J, Lucarelli P Scacchi R, Bottini E (1980) The geneticcomponent of quantitative perinatal variables. An analysis of relations between erythrocyte acid phosphatase phenotype and birth weight, gestational age and serum bilirubin level in the first days of life. J Perinat Med 8:42–47

    Google Scholar 

  • Dissing J (1987) Immunochemical characterization of human red cell acid phosphatase isozymes. Biochem Genet 25:901–917

    Google Scholar 

  • Dissing J (1992) Genetic and molecular aspects of the human red cell acid phosphatase polymorphism. In Rittner C, Schneider PM (eds) Advances in forensic haemogenetics, vol 4. Springer, Berlin, pp 303–305

    Google Scholar 

  • Dissing J (1993) Human “red cell” acid phosphatase (ACP1) genetic, catalytic and molecular properties. PhD thesis. Kobenhavn Universitat, Kobenhavn, Denmark

    Google Scholar 

  • Dissing J, Johnsen AH (1990) Human red cell acid phosphatase (ACP1): the primary structure of the two isozymes Bf and Bs encoded by the ACP1*B allele. In: Polesky HF, Mayr WR (eds) Advances in forensic haemogenetics. vol 3. Springer, Berlin, pp 211–213

    Google Scholar 

  • Dissing J, Johnsen AH (1992) Human red cell acid phosphatase (ACP1) — the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles. Biochim Biophys Acta 1121:261–268

    Google Scholar 

  • Dissing J, Sensabaugh GF (1987) Human red cell acid phosphatase (ACP1): evidence for differences in the primary structure of the two isozymes encoded by ACP1*B allele. Biochem Genet 25:919–927

    Google Scholar 

  • Dissing J, Svensmark O (1976) Human red cell acid phosphatase: quantitative evidence of a silent gene PO and a Danish population study. Hum Hered 26:43–58

    Google Scholar 

  • Dissing J, Dahl O, Svensmark O (1979) Phosphonic and arsonic acids as inhibitors of human red cells acid phosphatase and their use in affinity chromatography. Biochim Biophys Acta 569:159–176

    Google Scholar 

  • Dissing J, Johnson AH, Sensabaugh GF (1991) Human red cell acid phosphatase (ACP1) — the amino acid sequence of the 2 isozymes Bf and Bs encoded by the ACP1*B alleles. J Biol Chem 266:20619–20625

    Google Scholar 

  • Dissing J, Rangaard B, Christensen U (1993) Activity modulation of the fast and slow isozymes of human cytosolic low molecular weight acid phosphatase (ACP1) by purines. Biochim Biophys Acta 1162:275–282

    Google Scholar 

  • Fletcher RH, Fletcher SW, Wagner EH (1988) Clinical epidemiology — The essentials, 2nd edn. Williams and Wilkins, Baltimore

    Google Scholar 

  • Fuchs KR, Shekels LL, Bernlohr DA (1992) Analysis of the ACP1 gene product — classification as an FMN phosphatase. Biochem Biophys Res Commun 189:1598–1605

    PubMed  Google Scholar 

  • Glatzle D, Vuilleumier JP, Weber F, Decker K (1974) Glutathione reductase test with whole blood. A convenient procedure for the assessment of the riboflavin status in humans. Experientia 30:665–668

    Google Scholar 

  • Gloria-Bottini F, Gerlini G, Lucarini N, Borgiani P, Gori MC, Amante A, Lucarelli P, Bottini E (1988) Foetal macrosomia and ACP1 polymorphism in diabetic and normal pregnancy. Early Hum Devel 17:265–274

    Google Scholar 

  • Harris H, Hopkinson DA (1976) Handbook of enzyme electrophoresis in human genetics. North Holland, Amsterdam

    Google Scholar 

  • Harrison ML, Rathinavelu P, Arese P, Geahlen RL, Low PS 1991 Role of band 3 tyrosine phosphorylation in the regulation of erythrocyte glycolysis. J Biol Chem 266:4106–4111

    CAS  PubMed  Google Scholar 

  • Herbich J, Meinhart K (1972) The rare “silent” allele PO or PV (Pvienna) of human red cell acid phosphatase typed in a second family. Hum Genet 15:345–348

    Google Scholar 

  • Herbich J, Fisher RA, Hopkinson DA (1970) Atypical segregation of human red cell acid phosphatase phenotypes: evidence for a rare “silent” allele PO. Ann Hum Genet 34:145–151

    Google Scholar 

  • Hopkinson DA (1985) The discovery of the red cell acid phosphatase polymorphism. Vox Sang 49:77–80

    Google Scholar 

  • Hopkinson DA, Spencer N, Harris H (1963) Red cell acid phosphatase variants: a new human polymorphism. Nature 199:969–971

    Google Scholar 

  • Lazaruk AKD, Dissing J, Sensabaugh GF (1993) Exon structure at the human ACP1 locus supports alternative splicing model for f and s isozyme generation. Biochem Biophys Res Comm 196:440–446

    Google Scholar 

  • Lepore A, Lucarini N, Evangelista MA, Palombaro G, Londrillo A, Ballarini P, Borgiani P, Gloria-Bottini F, Bottini E (1989) Enzyme variability and neonatal jaundice. The role of adenosine deaminase and acid phosphatase. J Perinat Med 17:195–201

    Google Scholar 

  • Little RE, Mohrenweiser HW, Walters E (1989) Erythrocyte acid phosphatase phenotype and gestational length: no relationship in a sample of 3001 births. Early Hum Devel 20:151–154

    Google Scholar 

  • Manao G, Pazzagli L, Cirri P, Caselli A, Camici G, Cappugi G, Saeed A, Ramponi G (1992) Rat liver low Mr phosphotyrosine protein phosphatase isoenzymes — purification and amino acid sequence. J Protein Chem 11:333–345

    Google Scholar 

  • Mansfield E, Sensabaugh GF (1978) Red cell acid phosphatase: modulation of activity by purines. In: Brewer GJ (ed) The red cell. Allan R. Liss, New York, pp 233–247

    Google Scholar 

  • Modiano G, Filippi G, Brunelli P, Frattaroli W, Siniscalco M (1967) Studies on red cell acid phosphatase in Sardinia and Rome: absence of correlation with past malarial morbidity. Acta Genet Basel 17:17–28

    Google Scholar 

  • Mohrenweiser HW, Novotny JE (1982) A low-activity variant of human erythrocyte acid phosphatase: association with increased glutathione reductase activity. Am J Hum Genet 34:425–433

    Google Scholar 

  • Nichoalds GE, Lawrence JD, Sauberlich HE (1974) Assessment of status of riboflavin nutrition by assay of erythrocyte glutathione reductase activity. Clin Chem 20:624–628

    Google Scholar 

  • Nie NH, Hull CH, Jenkins JG, Steinbrenner K, Bent DH (1975) Statistical package for the social sciences. McGraw Hill, New York

    Google Scholar 

  • Oski FA, Komazawa M (1975) Metabolism of the erythrocytes of the newborn infant. Semin Hematol 12:209–221

    Google Scholar 

  • Paggi A, Borgiani P, Gloria-Bottini F, Russo S, Saponara I, Banci M, Amante A, Lucarini N, Bottini E (1991) Further studies on acid phosphatase in obese subjects. Dis Markers 9:1–7

    Google Scholar 

  • Palmarino R, Agostino R, Gloria F, Lucarelli P, Businco L, Antognoni G, Maggioni G, Workman PL, Bottini (1975) Red cell acid phosphatase: another polymorphism correlated with malaria? Am J Phys Anthropol 43:177–186

    Google Scholar 

  • Panara F, Angiolillo A, Secca T, Dirosa I, Fagotti A, Pascolini R (1991) Acid phosphatases in the frog (Ranaesculenta) skeletal muscle — purification and some properties of the low molecular weight enzyme. Int J Biochem 23:1115–1122

    Google Scholar 

  • Plomin R, Owen MJ, McGuffin P (1994) The genetic basis of complex human behaviors. Science 264:1733–1739

    Google Scholar 

  • Ramponi G, Manao G, Camici G, Cappugi G, Ruggiero M, Bottaro DP (1989) The 28 kDa cytosolic acid phosphatase from bovine liver has phosphotyrosine phosphatase activity on the autophosphorylated epidermal growth factor receptor. FEBS Lett 250:469–473

    Google Scholar 

  • Rohlf FS, Sokal RR (1981) Statistical tables, 2nd edn. W. H. Freeman, New York

    Google Scholar 

  • Searle AG, Peters J, Lyon MF, Hall JG, Evans EP, Edwards JH, Buckle VJ (1989) Chromosome maps of man and mouse. IV. Ann Hum Genet, 53:89–140

    Google Scholar 

  • Stefani M, Caselli A, Bucciantini M, Pazzagli L, Dolfi F, Camici G, Manao G, Ramponi G (1993) Dephosphorylation of tyrosine phosphorylated synthetic peptides by rat liver phosphotyrosine protein phosphatase isoenzymes. FEBS Lett 326:131–134

    Google Scholar 

  • Su SD, Taddei N, Stefani M, Ramponi G, Nordland P (1994) The crystal structure of a low-molecular weight phosphotyrosine protein phosphatase. Nature 270:575–578

    Google Scholar 

  • Taga EM, Van Etten RL (1982) Human liver acid phosphatases: purification and properties of a low-molecular-weight isoenzyme. Arch Biochem Biophys 214:505–515

    Google Scholar 

  • Tainer J, Russell P (1994) Cracking tyrosine phosphatases. Nature 370:506–507

    Google Scholar 

  • Ward RD, Sarfarazi M, Azimi-Garakani C, Beardmore JA (1986) Genetic polymorphism and a search for genetic influences on morbidity in the newborn. In: Harper PS, Sunderland E (eds) Genetic and population studies in Wales. University of Wales Press, Cardiff, p 342

    Google Scholar 

  • Wo YYP, McCormack AL, Shabanowitz J, Hunt DF, Davis JP, Mitchell GL, van Etten RL (1992a) Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase. J Biol Chem 267:10856–10865

    Google Scholar 

  • Wo YYP, Zhou MM, Stevis P, Davis JP, Zhang ZY, van Etten RL (1992b) Cloning, expression, and catalytic mechanism of the low molecular weight phsophotyrosyl protein phosphatase from bovine heart. Biochemistry 31:1712–1721

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bottini, E., Gloria-Bottini, F. & Borgiani, P. ACP1 and human adaptability 1. Association with common diseases: a case-control study. Hum Genet 96, 629–637 (1995). https://doi.org/10.1007/BF00210290

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00210290

Keywords

Navigation