A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

Genes and Immunity

Volumn 14, Issue 7, 2013, Pages 441-446

  Revez, J A ^a   Bain, L ^a   Chapman, B ^a   Powell, J E ^b   Jansen, R ^c,d   Duffy, D L ^a   Tung, J Y ^e   Collaborators, A A G C ^d   Matheson, Melanie C ^d   Marks, Guy B ^d   Hui, Jennie ^d   Le Souëf, Peter ^d   Danoy, Patrick ^d   Baltic, Svetlana ^d   Nyholt, Dale R ^d   Jenkins, Mark ^d   Hayden, Catherine ^d   Beilby, John ^d   Cheah, Faang ^d   Madden, Pamela A ^d   Heath, Andrew C ^d   Hopper, John L ^d   Musk, Bill ^d   Leeder, Stephen R ^d   Walters, Eugene H ^d   James, Alan ^d   Jones, Graham ^d   Abramson, Michael J ^d   Robertson, Colin F ^d   Dharmage, Shyamali C ^d   Brown, Matthew A ^d   Thompson, Philip J ^d   Penninx, B W ^c,d   Visscher, P M ^b   De Geus, E J C ^c,f   Boomsma, D I ^c,d,f   Hinds, D A ^e   Martin, N G ^a   Montgomery, G W ^a   Ferreira, M A R ^a   more..

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF QUEENSLAND   (Australia)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^d Neuroscience Campus Amsterdam ^*

^e Mountain View ^*  (United States)

^f VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; INTERLEUKIN 6 RECEPTOR; MESSENGER RNA; TOCILIZUMAB;

ADULT; ALLELE; ARTICLE; ASTHMA; BLOOD LEVEL; CONTROLLED STUDY; CORRELATION ANALYSIS; FEMALE; GENE; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HUMAN; IL6R GENE; INTRON; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

ADOLESCENT; ADULT; AGED; ASTHMA; CASE-CONTROL STUDIES; CHILD; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, INTERLEUKIN-6; RNA, MESSENGER;

EID: 84886723373     PISSN: 14664879     EISSN: 14765470     Source Type: Journal    
DOI: 10.1038/gene.2013.38     Document Type: Article

References (37)

1. Murphy DM, O'Byrne PM. Recent advances in the pathophysiology of asthma. Chest 2010; 137: 1417-1426.
2. Doganci A, Sauer K, Karwot R, Finotto S. Pathological role of IL-6 in the experimental allergic bronchial asthma in mice. Clin Rev Allergy Immunol 2005; 28: 257-270.
3. Neveu WA, Allard JL, Raymond DM, Bourassa LM, Burns SM, Bunn JY et al. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function. Respir Res 2010; 11: 28.
4. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol Sci 2012; 8: 1281-1290.
5. Wang J, Homer RJ, Chen Q, Elias JA. Endogenous and exogenous IL-6 inhibit aeroallergen-induced Th2 inflammation. J Immunol 2000; 165: 4051-4061.
6. Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T. Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 1990; 63: 1149-1157.
7. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 1989; 58: 573-581.
8. Chalaris A, Rabe B, Paliga K, Lange H, Laskay T, Fielding CA et al. Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils. Blood 2007; 110: 1748-1755.
9. Oberg HH, Wesch D, Grussel S, Rose-John S, Kabelitz D. Differential expression of CD126 and CD130 mediates different STAT-3 phosphorylation in CD4+CD25-and CD25high regulatory T cells. Int Immunol 2006; 18: 555-563.
10. Horiuchi S, Koyanagi Y, Zhou Y, Miyamoto H, Tanaka Y, Waki M et al. Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur J Immunol 1994; 24: 1945-1948.
11. Lust JA, Donovan KA, Kline MP, Greipp PR, Kyle RA, Maihle NJ. Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. Cytokine 1992; 4: 96-100.
12. Mullberg J, Schooltink H, Stoyan T, Gunther M, Graeve L, Buse G et al. The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol 1993; 23: 473-480.
13. Rose-John S, Heinrich PC. Soluble receptors for cytokines and growth factors: Generation and biological function. Biochem J 1994; 300: Pt 2 281-290.
14. Galicia JC, Tai H, Komatsu Y, Shimada Y, Akazawa K, Yoshie H. Polymorphisms in the IL-6 receptor (IL-6R) gene: Strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun 2004; 5: 513-516.
15. Mullberg J, Oberthur W, Lottspeich F, Mehl E, Dittrich E, Graeve L et al. The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. J Immunol 1994; 152: 4958-4968.
16. Doganci A, Eigenbrod T, Krug N, De Sanctis GT, Hausding M, Erpenbeck VJ et al. The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J Clin Invest 2005; 115: 313-325.
17. Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souef P et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 2011; 378: 1006-1014.
18. Rafiq S, Frayling TM, Murray A, Hurst A, Stevens K, Weedon MN et al. A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun 2007; 8: 552-559.
19. Raggi P, Su S, Karohl C, Veledar E, Rojas-Campos E, Vaccarino V. Heritability of renal function and inflammatory markers in adult male twins. Am J Nephrol 2010; 32: 317-323.
20. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE et al. An integrated map of genetic variation from 1, 092 human genomes. Nature 2012; 491: 56-65.
21. Yang J, Ferreira T, Morris AP, Medland SE, Madden PA, Heath AC et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet 2012; 444: 369-375, S1-3.
22. Melzer D, Perry JR, Hernandez D, Corsi AM, Stevens K, Rafferty I et al. A genomewide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet 2008; 4: E1000072.
23. Ferreira RC, Freitag DF, Cutler AJ, Howson JM, Rainbow DB, Smyth DJ et al. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLoS Genet 2013; 9: E1003444.
24. Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F et al. An integrated encyclopedia of DNA elements in the human genome. Nature 2012; 489: 57-74.
25. Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, Leo P et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 2013; 45: 730-738.
26. Hingorani AD, Casas JP. The interleukin-6 receptor as a target for prevention of coronary heart disease: A mendelian randomisation analysis. Lancet 2012; 379: 1214-1224.
27. Medland SE, Nyholt DR, Painter JN, McEvoy BP, McRae AF, Zhu G et al. Common variants in the trichohyalin gene are associated with straight hair in Europeans. Am J Hum Genet 2009; 85: 750-755.
28. Ferreira MA, O'Gorman L, Le Souef P, Burton PR, Toelle BG, Robertson CF et al. Variance components analyses of multiple asthma traits in a large sample of Australian families ascertained through a twin proband. Allergy 2006; 61: 245-253.
29. Powell JE, Henders AK, McRae AF, Caracella A, Smith S, Wright MJ et al. The Brisbane Systems Genetics Study: Genetical genomics meets complex trait genetics. PLoS One 2012; 7: E35430.
30. Zhu G, Montgomery GW, James MR, Trent JM, Hayward NK, Martin NG et al. A genome-wide scan for naevus count: Linkage to CDKN2A and to other chromosome regions. Eur J Hum Genet 2007; 15: 94-102.
31. Boomsma DI, Willemsen G, Sullivan PF, Heutink P, Meijer P, Sondervan D et al. Genome-wide association of major depression: Description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects. Eur J Hum Genet 2008; 16: 335-342.
32. Willemsen G, Vink JM, Abdellaoui A, den Braber A, van Beek JH, Draisma HH et al. The Adult Netherlands Twin Register: Twenty-five years of survey and biological data collection. Twin Res Hum Genet 2013; 16: 271-281.
33. Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S et al. A largescale, consortium-based genomewide association study of asthma. N Engl J Med 2010; 363: 1211-1221.
34. Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 2009; 5: E1000529.
35. Li Y, Willer C, Sanna S, Abecasis G. Genotype imputation. Annu Rev Genomics Hum Genet 2009; 10: 387-406.
36. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: Using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 2010; 34: 816-834.
37. Willer CJ, Li Y, Abecasis GR. METAL: Fast and efficient meta-analysis of genomewide association scans. Bioinformatics 2010; 26: 2190-2191.