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. 1999 May;36(5):379–382.

Linkage and association studies of atopy and the chromosome 11q13 region

K Deichmann 1, B Starke 1, S Schlenther 1, A Heinzmann 1, S H Sparholt 1, J Forster 1, J Kuehr 1
PMCID: PMC1734373  PMID: 10353783

Abstract

The clinical syndrome atopy is largely determined by genetic factors. In 1989, the first linkage of markers within and flanking the chromosomal region 11q13 and atopy was reported. In the following years, the gene coding for the β chain of the high affinity IgE receptor was localised to this region and two polymorphisms in this gene have been shown to be associated with the atopic phenotype.   We investigated two independent populations (population based and outpatient department) with different degrees of clinical symptoms. Using highly polymorphic markers we could find no evidence for linkage or allelic association of this particular genomic region to the atopic phenotype defined by enhanced IgE responsiveness (p>0.05). Neither did we succeed in finding either of the two polymorphisms described, nor could we identify any other polymorphisms within the gene. However, we found weak evidence for linkage in asthmatic sib pairs regarding maternal alleles (p=0.03).   We conclude from our data that in our populations the gene for the β chain of the high affinity IgE receptor is of minor importance for enhanced IgE responsiveness, and that it might influence atopy with clinical signs like asthma through maternally derived alleles.


Keywords: atopy; 11q13; association; linkage

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Selected References

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  1. Aberg N. Familial occurrence of atopic disease: genetic versus environmental factors. Clin Exp Allergy. 1993 Oct;23(10):829–834. doi: 10.1111/j.1365-2222.1993.tb00260.x. [DOI] [PubMed] [Google Scholar]
  2. Amelung P. J., Postma D. S., Xu J., Meyers D. A., Bleecker E. R. Exclusion of chromosome 11q and the FcepsilonRI-beta gene as aetiological factors in allergy and asthma in a population of Dutch asthmatic families. Clin Exp Allergy. 1998 Apr;28(4):397–403. doi: 10.1046/j.1365-2222.1998.00262.x. [DOI] [PubMed] [Google Scholar]
  3. Blackwelder W. C., Elston R. C. A comparison of sib-pair linkage tests for disease susceptibility loci. Genet Epidemiol. 1985;2(1):85–97. doi: 10.1002/gepi.1370020109. [DOI] [PubMed] [Google Scholar]
  4. Collée J. M., ten Kate L. P., de Vries H. G., Kliphuis J. W., Bouman K., Scheffer H., Gerritsen J. Allele sharing on chromosome 11q13 in sibs with asthma and atopy. Lancet. 1993 Oct 9;342(8876):936–936. doi: 10.1016/0140-6736(93)91988-x. [DOI] [PubMed] [Google Scholar]
  5. Cookson W. O., Sharp P. A., Faux J. A., Hopkin J. M. Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome 11q. Lancet. 1989 Jun 10;1(8650):1292–1295. doi: 10.1016/s0140-6736(89)92687-1. [DOI] [PubMed] [Google Scholar]
  6. Cookson W. O., Young R. P., Sandford A. J., Moffatt M. F., Shirakawa T., Sharp P. A., Faux J. A., Julier C., Nakumuura Y., Nakumura Y. Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet. 1992 Aug 15;340(8816):381–384. doi: 10.1016/0140-6736(92)91468-n. [DOI] [PubMed] [Google Scholar]
  7. Daniels S. E., Shirakawa T. A dinucleotide repeat polymorphism in the FCERIB gene. Hum Mol Genet. 1994 Jan;3(1):213–213. doi: 10.1093/hmg/3.1.213. [DOI] [PubMed] [Google Scholar]
  8. Duffy D. L., Healey S. C., Chenevix-Trench G., Martin N. G., Weger J., Lichter J. Atopy in Australia. Nat Genet. 1995 Jul;10(3):260–260. doi: 10.1038/ng0795-260a. [DOI] [PubMed] [Google Scholar]
  9. Hill M. R., Cookson W. O. A new variant of the beta subunit of the high-affinity receptor for immunoglobulin E (Fc epsilon RI-beta E237G): associations with measures of atopy and bronchial hyper-responsiveness. Hum Mol Genet. 1996 Jul;5(7):959–962. doi: 10.1093/hmg/5.7.959. [DOI] [PubMed] [Google Scholar]
  10. Hill M. R., James A. L., Faux J. A., Ryan G., Hopkin J. M., le Söuef P., Musk A. W., Cookson W. O. Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample. BMJ. 1995 Sep 23;311(7008):776–779. doi: 10.1136/bmj.311.7008.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hiort O., Wodtke A., Struve D., Zöllner A., Sinnecker G. H. Detection of point mutations in the androgen receptor gene using non-isotopic single strand conformation polymorphism analysis. German Collaborative Intersex Study Group. Hum Mol Genet. 1994 Jul;3(7):1163–1166. doi: 10.1093/hmg/3.7.1163. [DOI] [PubMed] [Google Scholar]
  12. Holgate S. T. Asthma genetics: waiting to exhale. Nat Genet. 1997 Mar;15(3):227–229. doi: 10.1038/ng0397-227. [DOI] [PubMed] [Google Scholar]
  13. Ishizaka K., Ishizaka T. Mechanisms of reaginic hypersensitivity: a review. Clin Allergy. 1971 Mar;1(1):9–24. doi: 10.1111/j.1365-2222.1971.tb02444.x. [DOI] [PubMed] [Google Scholar]
  14. Kjellman N. M., Johansson S. G., Roth A. Serum IgE levels in healthy children quantified by a sandwich technique (PRIST). Clin Allergy. 1976 Jan;6(1):51–59. doi: 10.1111/j.1365-2222.1976.tb01411.x. [DOI] [PubMed] [Google Scholar]
  15. Kleine-Tebbe J., Eickholt M., Gätjen M., Brunnée T., O'Connor A., Kunkel G. Comparison between MAGIC LITE- and CAP-system: two automated specific IgE antibody assays. Clin Exp Allergy. 1992 Apr;22(4):475–484. doi: 10.1111/j.1365-2222.1992.tb00150.x. [DOI] [PubMed] [Google Scholar]
  16. Kuehr J., Karmaus W., Forster J., Frischer T., Hendel-Kramer A., Moseler M., Stephan V., Urbanek R., Weiss K. Sensitization to four common inhalant allergens within 302 nuclear families. Clin Exp Allergy. 1993 Jul;23(7):600–605. doi: 10.1111/j.1365-2222.1993.tb00900.x. [DOI] [PubMed] [Google Scholar]
  17. Kuehr J., Karmaus W., Frischer T., Hendel-Kramer A., Weiss K., Moseler M., Stephan V., Forster J., Urbanek R. Longitudinal variability of skin prick test results. Clin Exp Allergy. 1992 Sep;22(9):839–844. doi: 10.1111/j.1365-2222.1992.tb02829.x. [DOI] [PubMed] [Google Scholar]
  18. Küster H., Zhang L., Brini A. T., MacGlashan D. W., Kinet J. P. The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor. J Biol Chem. 1992 Jun 25;267(18):12782–12787. [PubMed] [Google Scholar]
  19. Moffatt M. F. Dinucleotide repeat polymorphism at the D11S480 locus. Hum Mol Genet. 1993 Apr;2(4):492–492. doi: 10.1093/hmg/2.4.492. [DOI] [PubMed] [Google Scholar]
  20. Morton N. E. Major loci for atopy? Clin Exp Allergy. 1992 Dec;22(12):1041–1043. doi: 10.1111/j.1365-2222.1992.tb00126.x. [DOI] [PubMed] [Google Scholar]
  21. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  22. Risch N., Merikangas K. The future of genetic studies of complex human diseases. Science. 1996 Sep 13;273(5281):1516–1517. doi: 10.1126/science.273.5281.1516. [DOI] [PubMed] [Google Scholar]
  23. Sandford A. J., Shirakawa T., Moffatt M. F., Daniels S. E., Ra C., Faux J. A., Young R. P., Nakamura Y., Lathrop G. M., Cookson W. O. Localisation of atopy and beta subunit of high-affinity IgE receptor (Fc epsilon RI) on chromosome 11q. Lancet. 1993 Feb 6;341(8841):332–334. doi: 10.1016/0140-6736(93)90136-5. [DOI] [PubMed] [Google Scholar]
  24. Sandford A., Weir T., Paré P. The genetics of asthma. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1749–1765. doi: 10.1164/ajrccm.153.6.8665031. [DOI] [PubMed] [Google Scholar]
  25. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shirakawa T., Hashimoto T., Furuyama J., Takeshita T., Morimoto K. Linkage between severe atopy and chromosome 11q13 in Japanese families. Clin Genet. 1994 Sep;46(3):228–232. doi: 10.1111/j.1399-0004.1994.tb04231.x. [DOI] [PubMed] [Google Scholar]
  27. Shirakawa T., Li A., Dubowitz M., Dekker J. W., Shaw A. E., Faux J. A., Ra C., Cookson W. O., Hopkin J. M. Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor. Nat Genet. 1994 Jun;7(2):125–129. doi: 10.1038/ng0694-125. [DOI] [PubMed] [Google Scholar]
  28. Shirakawa T., Mao X. Q., Sasaki S., Enomoto T., Kawai M., Morimoto K., Hopkin J. Association between atopic asthma and a coding variant of Fc epsilon RI beta in a Japanese population. Hum Mol Genet. 1996 Aug;5(8):1129–1130. doi: 10.1093/hmg/5.8.1129. [DOI] [PubMed] [Google Scholar]
  29. Spielman R. S., McGinnis R. E., Ewens W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed] [Google Scholar]
  30. Weeks D. E., Lathrop G. M. Polygenic disease: methods for mapping complex disease traits. Trends Genet. 1995 Dec;11(12):513–519. doi: 10.1016/s0168-9525(00)89163-5. [DOI] [PubMed] [Google Scholar]
  31. Young R. P., Sharp P. A., Lynch J. R., Faux J. A., Lathrop G. M., Cookson W. O., Hopkin J. M. Confirmation of genetic linkage between atopic IgE responses and chromosome 11q13. J Med Genet. 1992 Apr;29(4):236–238. doi: 10.1136/jmg.29.4.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van Herwerden L., Harrap S. B., Wong Z. Y., Abramson M. J., Kutin J. J., Forbes A. B., Raven J., Lanigan A., Walters E. H. Linkage of high-affinity IgE receptor gene with bronchial hyperreactivity, even in absence of atopy. Lancet. 1995 Nov 11;346(8985):1262–1265. doi: 10.1016/s0140-6736(95)91863-9. [DOI] [PubMed] [Google Scholar]

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