Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1998 Jun;35(6):502–504. doi: 10.1136/jmg.35.6.502

Linkage and association of an interleukin 4 gene polymorphism with atopic dermatitis in Japanese families.

T Kawashima 1, E Noguchi 1, T Arinami 1, K Yamakawa-Kobayashi 1, H Nakagawa 1, F Otsuka 1, H Hamaguchi 1
PMCID: PMC1051346  PMID: 9643293

Abstract

We examined linkage between markers at and near the IL4 gene and atopic dermatitis (AD) in 88 Japanese nuclear families. Affected sib pair analysis suggested linkage between the IL4 gene and AD (SPLINK lod=2.28). Transmission disequilibrium testing showed a significantly preferential transmission to AD offspring of the T allele of the -590C/T polymorphism of the IL4 gene (p=0.001). A case-control comparison suggested a genotypic association of the TT genotype with AD (odds ratio=1.88, p=0.01). Since the T allele was reported to be associated with increased IL4 gene promoter activity compared with the C allele, our data indicate that genetic differences in transcriptional activity of the IL4 gene influence AD predisposition, particularly in Japanese, because of a high frequency of the T allele.

Full text

PDF
502

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blumenthal M. N., Banks-Schlegel S., Bleecker E. R., Marsh D. G., Ober C. Collaborative studies on the genetics of asthma--National Heart, Lung and Blood Institute. Clin Exp Allergy. 1995 Nov;25 (Suppl 2):29–32. doi: 10.1111/j.1365-2222.1995.tb00416.x. [DOI] [PubMed] [Google Scholar]
  2. Coleman R., Trembath R. C., Harper J. I. Chromosome 11q13 and atopy underlying atopic eczema. Lancet. 1993 May 1;341(8853):1121–1122. doi: 10.1016/0140-6736(93)93130-s. [DOI] [PubMed] [Google Scholar]
  3. Daniels S. E., Bhattacharrya S., James A., Leaves N. I., Young A., Hill M. R., Faux J. A., Ryan G. F., le Söuef P. N., Lathrop G. M. A genome-wide search for quantitative trait loci underlying asthma. Nature. 1996 Sep 19;383(6597):247–250. doi: 10.1038/383247a0. [DOI] [PubMed] [Google Scholar]
  4. Doull I. J., Lawrence S., Watson M., Begishvili T., Beasley R. W., Lampe F., Holgate T., Morton N. E. Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness. Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1280–1284. doi: 10.1164/ajrccm.153.4.8616554. [DOI] [PubMed] [Google Scholar]
  5. Hamid Q., Boguniewicz M., Leung D. Y. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994 Aug;94(2):870–876. doi: 10.1172/JCI117408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Holmans P., Clayton D. Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers. Am J Hum Genet. 1995 Nov;57(5):1221–1232. [PMC free article] [PubMed] [Google Scholar]
  7. Kruglyak L., Daly M. J., Reeve-Daly M. P., Lander E. S. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996 Jun;58(6):1347–1363. [PMC free article] [PubMed] [Google Scholar]
  8. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  9. Mao X. Q., Shirakawa T., Yoshikawa T., Yoshikawa K., Kawai M., Sasaki S., Enomoto T., Hashimoto T., Furuyama J., Hopkin J. M. Association between genetic variants of mast-cell chymase and eczema. Lancet. 1996 Aug 31;348(9027):581–583. doi: 10.1016/s0140-6736(95)10244-2. [DOI] [PubMed] [Google Scholar]
  10. Marsh D. G., Neely J. D., Breazeale D. R., Ghosh B., Freidhoff L. R., Ehrlich-Kautzky E., Schou C., Krishnaswamy G., Beaty T. H. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science. 1994 May 20;264(5162):1152–1156. doi: 10.1126/science.8178175. [DOI] [PubMed] [Google Scholar]
  11. Meyers D. A., Postma D. S., Panhuysen C. I., Xu J., Amelung P. J., Levitt R. C., Bleecker E. R. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5. Genomics. 1994 Sep 15;23(2):464–470. doi: 10.1006/geno.1994.1524. [DOI] [PubMed] [Google Scholar]
  12. Renz H., Jujo K., Bradley K. L., Domenico J., Gelfand E. W., Leung D. Y. Enhanced IL-4 production and IL-4 receptor expression in atopic dermatitis and their modulation by interferon-gamma. J Invest Dermatol. 1992 Oct;99(4):403–408. doi: 10.1111/1523-1747.ep12616114. [DOI] [PubMed] [Google Scholar]
  13. Rosenwasser L. J., Klemm D. J., Dresback J. K., Inamura H., Mascali J. J., Klinnert M., Borish L. Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy. 1995 Nov;25 (Suppl 2):74–96. doi: 10.1111/j.1365-2222.1995.tb00428.x. [DOI] [PubMed] [Google Scholar]
  14. Rousset F., Robert J., Andary M., Bonnin J. P., Souillet G., Chrétien I., Brière F., Pène J., de Vries J. E. Shifts in interleukin-4 and interferon-gamma production by T cells of patients with elevated serum IgE levels and the modulatory effects of these lymphokines on spontaneous IgE synthesis. J Allergy Clin Immunol. 1991 Jan;87(1 Pt 1):58–69. doi: 10.1016/0091-6749(91)90213-8. [DOI] [PubMed] [Google Scholar]
  15. Schleimer R. P., Sterbinsky S. A., Kaiser J., Bickel C. A., Klunk D. A., Tomioka K., Newman W., Luscinskas F. W., Gimbrone M. A., Jr, McIntyre B. W. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol. 1992 Feb 15;148(4):1086–1092. [PubMed] [Google Scholar]
  16. Vercelli D., Geha R. S. Regulation of IgE synthesis: from the membrane to the genes. Springer Semin Immunopathol. 1993;15(1):5–16. doi: 10.1007/BF00204622. [DOI] [PubMed] [Google Scholar]
  17. Vercelli D., Jabara H. H., Lauener R. P., Geha R. S. IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures. J Immunol. 1990 Jan 15;144(2):570–573. [PubMed] [Google Scholar]
  18. Walley A. J., Cookson W. O. Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy. J Med Genet. 1996 Aug;33(8):689–692. doi: 10.1136/jmg.33.8.689. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES