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Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1999 Apr;36(4):323–325.

Association of a lymphotoxin α gene polymorphism and atopy in Italian families

E Trabetti 1, C Patuzzo 1, G Malerba 1, R Galavotti 1, L C Martinati 1, A Boner 1, P F Pignatti 1
PMCID: PMC1734358  PMID: 10227402

Abstract

Tumour necrosis factor (TNF) is a proinflammatory cytokine that increases human airway tissue responsiveness and is considered a candidate gene for asthma. Two common polymorphisms (LTαNcoI and TNFα-308) in the TNF gene complex were studied in 600 subjects from 131 Italian families with atopic asthmatic children. Skin prick test (SPT), total IgE levels, atopy (defined as increased IgE levels or SPT positivity or both), bronchial hyperresponsiveness, and clinical asthma were investigated. The observed distribution of the identical by descent alleles at the LTαNcoI locus was different from expected for SPT and atopy (p=0.015). The LTαNcoI genotype distribution for increased IgE levels was different between males and females (p=0.0011), and an association of the 2.2 genotype with increased IgE levels was observed in females (p=0.0032). The results indicate that the LTα gene, or a closely linked locus, is associated with atopy, and suggest a sex difference in the effect of the gene.


Keywords: atopy; asthma; TNF; LTα

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Selected References

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  1. Albuquerque R. V., Hayden C. M., Palmer L. J., Laing I. A., Rye P. J., Gibson N. A., Burton P. R., Goldblatt J., Lesouëf P. N. Association of polymorphisms within the tumour necrosis factor (TNF) genes and childhood asthma. Clin Exp Allergy. 1998 May;28(5):578–584. doi: 10.1046/j.1365-2222.1998.00273.x. [DOI] [PubMed] [Google Scholar]
  2. Anticevich S. Z., Hughes J. M., Black J. L., Armour C. L. Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha. Eur J Pharmacol. 1995 Sep 15;284(1-2):221–225. doi: 10.1016/0014-2999(95)00463-u. [DOI] [PubMed] [Google Scholar]
  3. Aron Y., Desmazes-Dufeu N., Matran R., Polla B. S., Dusser D., Lockhart A., Swierczewski E. Evidence of a strong, positive association between atopy and the HLA class II alleles DR4 and DR7. Clin Exp Allergy. 1996 Jul;26(7):821–828. [PubMed] [Google Scholar]
  4. Blumenthal M., Marcus-Bagley D., Awdeh Z., Johnson B., Yunis E. J., Alper C. A. HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] haplotypes distinguish subjects with asthma from those with rhinitis only in ragweed pollen allergy. J Immunol. 1992 Jan 15;148(2):411–416. [PubMed] [Google Scholar]
  5. Carroll M. C., Katzman P., Alicot E. M., Koller B. H., Geraghty D. E., Orr H. T., Strominger J. L., Spies T. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8535–8539. doi: 10.1073/pnas.84.23.8535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. D'Amato M., Scotto d'Abusco A., Maggi E., Menna T., Sacerdoti G., Maurizio S. M., Iozzino S., De Santo C., Oreste U., Tosi R. Association of responsiveness to the major pollen allergen of Parietaria officinalis with HLA-DRB1* alleles: a multicenter study. Hum Immunol. 1996 Apr;46(2):100–106. doi: 10.1016/0198-8859(96)00012-2. [DOI] [PubMed] [Google Scholar]
  7. Duffy D. L., Martin N. G., Battistutta D., Hopper J. L., Mathews J. D. Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1351–1358. doi: 10.1164/ajrccm/142.6_Pt_1.1351. [DOI] [PubMed] [Google Scholar]
  8. Hopp R. J., Bewtra A. K., Biven R., Nair N. M., Townley R. G. Bronchial reactivity pattern in nonasthmatic parents of asthmatics. Ann Allergy. 1988 Sep;61(3):184–186. [PubMed] [Google Scholar]
  9. Martinati L. C., Trabetti E., Casartelli A., Boner A. L., Pignatti P. F. Affected sib-pair and mutation analyses of the high affinity IgE receptor beta chain locus in Italian families with atopic asthmatic children. Am J Respir Crit Care Med. 1996 May;153(5):1682–1685. doi: 10.1164/ajrccm.153.5.8630620. [DOI] [PubMed] [Google Scholar]
  10. Messer G., Spengler U., Jung M. C., Honold G., Blömer K., Pape G. R., Riethmüller G., Weiss E. H. Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med. 1991 Jan 1;173(1):209–219. doi: 10.1084/jem.173.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moffatt M. F., Cookson W. O. Tumour necrosis factor haplotypes and asthma. Hum Mol Genet. 1997 Apr;6(4):551–554. doi: 10.1093/hmg/6.4.551. [DOI] [PubMed] [Google Scholar]
  12. Sears M. R., Burrows B., Flannery E. M., Herbison G. P., Hewitt C. J., Holdaway M. D. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med. 1991 Oct 10;325(15):1067–1071. doi: 10.1056/NEJM199110103251504. [DOI] [PubMed] [Google Scholar]
  13. Shah A., Church M. K., Holgate S. T. Tumour necrosis factor alpha: a potential mediator of asthma. Clin Exp Allergy. 1995 Nov;25(11):1038–1044. doi: 10.1111/j.1365-2222.1995.tb03249.x. [DOI] [PubMed] [Google Scholar]
  14. Sham P. C., Curtis D. An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Ann Hum Genet. 1995 Jul;59(Pt 3):323–336. doi: 10.1111/j.1469-1809.1995.tb00751.x. [DOI] [PubMed] [Google Scholar]
  15. Sibbald B., Turner-Warwick M. Factors influencing the prevalence of asthma among first degree relatives of extrinsic and intrinsic asthmatics. Thorax. 1979 Jun;34(3):332–337. doi: 10.1136/thx.34.3.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Trabetti E., Cusin V., Malerba G., Martinati L. C., Casartelli A., Boner A. L., Pignatti P. F. Association of the FcepsilonRIbeta gene with bronchial hyper-responsiveness in an Italian population. J Med Genet. 1998 Aug;35(8):680–681. doi: 10.1136/jmg.35.8.680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Weiss S. T., Tager I. B., Weiss J. W., Munoz A., Speizer F. E., Ingram R. H. Airways responsiveness in a population sample of adults and children. Am Rev Respir Dis. 1984 Jun;129(6):898–902. doi: 10.1164/arrd.1984.129.6.898. [DOI] [PubMed] [Google Scholar]
  18. Wilson A. G., de Vries N., Pociot F., di Giovine F. S., van der Putte L. B., Duff G. W. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med. 1993 Feb 1;177(2):557–560. doi: 10.1084/jem.177.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wilson A. G., di Giovine F. S., Blakemore A. I., Duff G. W. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet. 1992 Aug;1(5):353–353. doi: 10.1093/hmg/1.5.353. [DOI] [PubMed] [Google Scholar]

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