Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

A population genetics study of single nucleotide polymorphisms in the interleukin 4 receptor α (IL4RA) gene

Genes & Immunity volume 2, pages 128–134 (2001)Cite this article

Abstract

Interleukin 4 (IL4) plays a critical role in T helper 2 (Th2) immune responses. Here we report a population genetics study of variation in the gene encoding the α-chain of the IL4 receptor (IL4RA) in three ethnic groups: African Americans, European Americans and East Asians. A 2941-bp region spanning exon 12 of IL4RA gene was sequenced in 12 individuals from each group. A total of 24 single nucleotide polymorphisms (SNPs) were identified in the combined sample. The genetic variation of the coding region of exon 12 is two to three times higher than in other reported genes. A significant departure from the expectation of evolutionary neutrality was observed, suggesting that natural selection may have influenced the evolution of this gene. We propose a model in which past selection by pathogens contributed to the increasing prevalence of atopic disorders in Western societies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Paul WE Interleukin-4: a prototypic immunoregulatory lymphokine Blood 1991 77 1859–1870

    CAS  PubMed  Google Scholar 

  2. Minty A, Chalon P, Derocq JM et al Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses Nature 1993 362 248–250

    Article  CAS  Google Scholar 

  3. Paul WE, Seder RA Lymphocyte responses and cytokines Cell 1994 76 241–251

    Article  CAS  Google Scholar 

  4. Punnonen J, Aversa G, Cocks BG et al Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells Proc Natl Acad Sci USA 1993 90 3730–3734

    Article  CAS  Google Scholar 

  5. Chomarat P, Banchereau J An update on interleukin-4 and its receptor Eur Cytokine Netw 1997 8 333–344

    CAS  PubMed  Google Scholar 

  6. Kruse S, Forster J, Kuehr J, Deichmann KA Characterization of the membrane bound and a soluble form of human IL4R produced by alternative splicing Int Immun 1999 11 1965–1970

    Article  CAS  Google Scholar 

  7. Deichmann K, Bardutzky J, Forster J, Heinzmann A, Kuehr J Common polymorphisms in the coding part of the IL4-receptor gene Biochem Biophys Res Communic 1997 231 696–697

    Article  CAS  Google Scholar 

  8. Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA The association of atopy with a gain-of-function mutation in the a subunit of the interleukin-4 receptor N Engl J Med 1997 337 1720–1725

    Article  CAS  Google Scholar 

  9. Kruse S, Japha T, Tedner M et al The polymorphisms S503P and Q576R in the interleukin-4 receptor a gene are associated with atopy and influence the signal transduction Immunology 1999 96 365–371

    Article  CAS  Google Scholar 

  10. Ober C, Leavitt SA, Tsalenko A et al Variation in the interleukin 4 receptor α gene confers susceptibility to asthma and atopy in ethnically diverse populations Am J Hum Genet 2000 66 517–526

    Article  CAS  Google Scholar 

  11. Mitsuyasu H, Izuhara K, Mao X-Q et al Ile50Val variant of IL4Ra upregulates IgE synthesis and associates with atopic asthma Nat Genet 1998 19 119–120

    Article  CAS  Google Scholar 

  12. Hackstein H, Hofmann H, Bohnert A, Bein G Definition of human interleukin-4 receptor alpha chain haplotypes and allelic association with atopy markers Hum Immunol 1999 60 1119–1127

    Article  CAS  Google Scholar 

  13. Kanemitsu S, Takabayashi A, Sasaki Y et al Association of interleukin-4 receptor and interleukin-4 promoter gene polymorphisms with systemic lupus erythematosus Arthritis Rheum 1999 42 1298–1300

    Article  CAS  Google Scholar 

  14. Youn J, Hwang SH, Cho CS et al Association of the interleukin-4 receptor alpha variant Q576R with Th1/Th2 imbalance in connective tissue disease Immunogenetics 2000 51 743–746

    Article  CAS  Google Scholar 

  15. Hackstein H, Kluter H, Fricke L, Hoyer J, Bein G The IL-4 receptor alpha-chain variant Q576R is strongly associated with decreased kidney allograft survival Tissue Antigens 1999 54 471–477

    Article  CAS  Google Scholar 

  16. Shirakawa T, Deichmann K, Izuhara K, Mao X-Q, Adra CN, Hopkin JM Atopy and asthma: genetic variants of IL-4 and IL-13 signalling Immunol Today 2000 21 60–64

    Article  CAS  Google Scholar 

  17. Harding RM, Fullerton SM, Griffiths RC et al Archaic African and Asian lineages in the genetic ancestry of modern humans Am J Hum Genet 1997 60 772–789

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Nickerson DA, Scott LT, Weiss KM et al DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene Nat Genet 1998 19 233–240

    Article  CAS  Google Scholar 

  19. Rieder JJ, Taylor SL, Clark AG, Nickerson DA Sequence variation in the human angiotensin converting enzyme Nat Genet 1999 22 59–62

    Article  CAS  Google Scholar 

  20. Cargill M, Altshuler D, Ireland J et al Characterization of single-nucleotide polymorphisms in coding regions of human genes Nat Genet 1999 22 231–238

    Article  CAS  Google Scholar 

  21. Halushka MK, Fan JB, Bentley K et al Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis Nat Genet 1999 22 239–247

    Article  CAS  Google Scholar 

  22. Goddard KA, Hopkins PJ, Hall JM, Witte JS Linkage disequilibrium and allele-frequency distributions for 114 single-nucleotide polymorphisms in five populations Am J Hum Genet 2000 66 216–234

    Article  CAS  Google Scholar 

  23. Przeworski M, Hudson RR, Di Rienzo A Adjusting the focus on human variation Trends Genet 2000 16 296–302

    Article  CAS  Google Scholar 

  24. Clark AG, Weiss KM, Nickerson DA et al Haplotype and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase Am J Hum Genet 1998 63 595–612

    Article  CAS  Google Scholar 

  25. Grimbacher B, Holland SM, Puck JM The interleukin-4 receptor variant Q576R in hyper-IgE syndrome [letter; comment] N Engl J Med 1998 338 1073–1074

    Article  CAS  Google Scholar 

  26. Strachan DP Hay fever, hygiene, and household size Br Med J 1989 299 1259–1260

    Article  CAS  Google Scholar 

  27. Romagnani S Regulation of the development of type 2 T-helper cells in allergy Curr Opin Immunol 1994 6 838–846

    Article  CAS  Google Scholar 

  28. Shirakawa T, Enomoto T, Shimazu S, Hopkin JM The inverse association between tuberculin responses and atopic disorder Science 1997 275 77–79

    Article  CAS  Google Scholar 

  29. Cookson W The alliance of genes and environment in asthma and allergy Nature 1999 402 B5–B11

    Article  CAS  Google Scholar 

  30. Shaheen SO, Aaby P, Hall AJ et al Measles and atopy in Guinea-Bissau Lancet 1996 347 1792–1796

    Article  CAS  Google Scholar 

  31. Matricardi PM, Rosmini F, Ferrigno L et al Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus BMJ 1997 314 999–1003

    Article  CAS  Google Scholar 

  32. McDonald JH, Kreitman M Adaptive protein evolution at the Adh locus in Drosophila Nature 1991 351 652–654

    Article  CAS  Google Scholar 

  33. Kimura M The Neutral Theory of Molecular Evolution Cambridge University Press: Cambridge 1983

    Book  Google Scholar 

  34. Tajima F Statistical method for testing the neutral mutation hypothesis by DNA polymorphism Genetics 1989 123 585–595

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Rozas J, Rozas R DnaSP version 3: an integrated program for molecular population genetics and molecular evolution analysis Bioinformatics 1999 15 174–175

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Carrie Grimsley, Martha Hamblin, and Anne Sperling for helpful discussions.

Author information

Authors and Affiliations

  1. Department of Human Genetics, the University of Chicago, Chicago, IL, USA

    X Wu, A Di Rienzo & C Ober

  2. Department of Statistics, the University of Chicago, Chicago, IL, USA

    X Wu

Authors
  1. X Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Di Rienzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Ober
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Ober.

Additional information

This work was supported in part by NIH grants HL49596 and HL56399, and NSF Group Infrastructure Grant DMS 97-09696.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, X., Di Rienzo, A. & Ober, C. A population genetics study of single nucleotide polymorphisms in the interleukin 4 receptor α (IL4RA) gene. Genes Immun 2, 128–134 (2001). https://doi.org/10.1038/sj.gene.6363746

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363746

Keywords

This article is cited by

Search

Advanced search

Quick links