RT Journal Article SR Electronic T1 Variation in the ICAM1–ICAM4–ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries JF Annals of the Rheumatic Diseases JO Ann Rheum Dis FD BMJ Publishing Group Ltd and European League Against Rheumatism SP 1809 OP 1814 DO 10.1136/annrheumdis-2011-201110 VO 71 IS 11 A1 Kwangwoo Kim A1 Elizabeth E Brown A1 Chan-Bum Choi A1 Marta E Alarcón-Riquelme A1 Jennifer A Kelly A1 Stuart B Glenn A1 Joshua O Ojwang A1 Adam Adler A1 Hye-Soon Lee A1 Susan A Boackle A1 Lindsey A Criswell A1 Graciela S Alarcón A1 Jeffrey C Edberg A1 Anne M Stevens A1 Chaim O Jacob A1 Gary S Gilkeson A1 Diane L Kamen A1 Betty P Tsao A1 Juan-Manuel Anaya A1 Joel M Guthridge A1 Swapan K Nath A1 Bruce Richardson A1 Amr H Sawalha A1 Young Mo Kang A1 Seung Cheol Shim A1 Chang-Hee Suh A1 Soo-Kon Lee A1 Chang-sik Kim A1 Joan T Merrill A1 Michelle Petri A1 Rosalind Ramsey-Goldman A1 Luis M Vilá A1 Timothy B Niewold A1 Javier Martin A1 Bernardo A Pons-Estel A1 Timothy J Vyse A1 Barry I Freedman A1 Kathy L Moser A1 Patrick M Gaffney A1 Adrienne Williams A1 Mary Comeau A1 John D Reveille A1 Judith A James A1 R Hal Scofield A1 Carl D Langefeld A1 Kenneth M Kaufman A1 John B Harley A1 Changwon Kang A1 Robert P Kimberly A1 Sang-Cheol Bae YR 2012 UL http://ard.bmj.com/content/71/11/1809.abstract AB Objective Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αM (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. Methods The authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. Results The A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5). Conclusion These findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.