Abstract
It is well known that subjects homozygous for a rare silent allele of ADA may experience a severe combined immunodeficiency. By analogy we have investigated the possible relationship of normal ADA polymorphism with some situations, such as reproductive defects and fetomaternal interactions, in which immunological mechanisms may play an important role. A total of 572 consecutive newborns, 93 consecutive low birthweight infants, 46 couples with unexplained habitual abortion, and 24 couples with unexplained sterility were studied. The proportion of ADA 2-1 phenotype was reduced in couples with reproductive defects. In the sample of consecutive newborns the proportion of ABO incompatible babies was higher among ADA 2-1 than among ADA 1 types. ADA 2-1 phenotype was also associated with a reduction in the variability of gestational length. These associations were much more marked among male than among female babies. The proportion of ADA 2-1 was significantly lower in low birthweight infants than in the consecutively studied infants and normal adults. The present data suggest that biochemical variability resulting from the normal ADA polymorphism may be, at least in part, responsible for the variability of some immunological functions and related physiological variables and pathological conditions. They also provide evidence in favour of a selective advantage of ADA heterozygotes.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Battistuzzi G., Scozzari R., Santolamazza P., Terrenato L., Modiano G. Comparative activity of red cell adenosine deaminase allelic forms. Nature. 1974 Oct 25;251(5477):711–713. doi: 10.1038/251711a0. [DOI] [PubMed] [Google Scholar]
- Cohen B. H. ABO and Rh incompatibility. I. Fetal and neonatal mortality aith ABO and Rh incompatibility. Some new interpretations. Am J Hum Genet. 1970 Jul;22(4):412–440. [PMC free article] [PubMed] [Google Scholar]
- Donofrio J., Coleman M. S., Hutton J. J., Daoud A., Lampkin B., Dyminski J. Overproduction of adenine deoxynucleosides and deoxynucletides in adenosine deaminase deficiency with severe combined immunodeficiency disease. J Clin Invest. 1978 Oct;62(4):884–887. doi: 10.1172/JCI109201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hershfield M. S. Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine and adenine arabinoside. A basis for direct toxic effects of analogs of adenosine. J Biol Chem. 1979 Jan 10;254(1):22–25. [PubMed] [Google Scholar]
- Hirschhorn R. Adenosine deaminase deficiency and immunodeficiencies. Fed Proc. 1977 Jul;36(8):2166–2170. [PubMed] [Google Scholar]
- Lucarelli P., Corbo R. M., Scacchi R., Palmarino R., Salsini G., Cristofori G., Osti L., Menini C., Vullo C., Bottini E. A study of nine polymorphic systems in the population of the Po Delta. Am J Phys Anthropol. 1976 Sep;45(2):211–216. doi: 10.1002/ajpa.1330450208. [DOI] [PubMed] [Google Scholar]
- Marone G., Lichtenstein L. M. Adenosine-adenosine deaminase modulation of histamine release from human basophils in vitro. Ric Clin Lab. 1979 Apr-Jun;9(2):131–139. doi: 10.1007/BF02904910. [DOI] [PubMed] [Google Scholar]
- Mitchell B. S., Mejias E., Daddona P. E., Kelley W. N. Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5011–5014. doi: 10.1073/pnas.75.10.5011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosen F. S. Enzyme defects and immune dysfunction. Nature. 1978 Dec 7;276(5688):559–560. doi: 10.1038/276559a0. [DOI] [PubMed] [Google Scholar]
- Scozzari R., Santolamazza C., Carapella E. Studies on the red cell adenosine deaminase polymorphism in Rome. Humangenetik. 1970;8(4):364–365. doi: 10.1007/BF00280340. [DOI] [PubMed] [Google Scholar]
- Takano K., Miller J. R. ABO incompatibility as a cause of spontaneous abortion: evidence from abortuses. J Med Genet. 1972 Jun;9(2):144–150. doi: 10.1136/jmg.9.2.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson J. M., Mitchell B. S., Daddona P. E., Kelley W. N. Purinogenic immunodeficiency diseases. Differential effects of deoxyadenosine and deoxyguanosine on DNA synthesis in human T lymphoblasts. J Clin Invest. 1979 Nov;64(5):1475–1484. doi: 10.1172/JCI109606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolberg G., Zimmerman T. P., Hiemstra K., Winston M., Chu L. C. Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. Science. 1975 Mar 14;187(4180):957–959. doi: 10.1126/science.167434. [DOI] [PubMed] [Google Scholar]