Genetic association study of systemic lupus erythematosus and disease subphenotypes in European populations

被引:17
作者
Ruiz-Larranaga, Otsanda [1 ]
Migliorini, Paola [2 ]
Uribarri, Maria [3 ]
Czirjak, Laszlo [4 ]
Alcaro, Maria C. [5 ]
del Amo, Jokin [3 ]
Iriondo, Mikel [1 ]
Manzano, Carmen [1 ]
Escorza-Trevino, Sergio [3 ]
Estonba, Andone [1 ]
机构
[1] Univ Basque Country, Genet Phys Anthropol & Anim Physiol Dept, UPV EHU, Leioa, Spain
[2] Univ Pisa, Dept Clin & Expt Med, Clin Immunol Unit, Pisa, Italy
[3] Progenika Biopharma SA, Dept Res & Dev, Derio, Spain
[4] Univ Pecs, Dept Rheumatol & Immunol, Pecs, Hungary
[5] Toscana Biomarkers Srl, Dept Res & Dev, Siena, Italy
关键词
Clinical manifestations; Genetics; Single nucleotide polymorphism; Systemic lupus; GENOME-WIDE ASSOCIATION; CHINESE HAN POPULATION; SUSCEPTIBILITY LOCI; RHEUMATOID-ARTHRITIS; FUNCTIONAL VARIANTS; RISK; POLYMORPHISMS; NEPHRITIS; METAANALYSIS; REPLICATION;
D O I
10.1007/s10067-016-3235-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Epidemiological studies suggest a strong contribution of genetic factors in the pathogenesis of systemic lupus erythematosus (SLE). In the last decades, many risk loci have been identified in several genetic association studies following both candidate gene and genome-wide approaches. The present work was conducted by GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium with a dual aim: to replicate the association of several previously reported SLE susceptibility loci in an independent European sample and to explore their relation with some disease subphenotypes. A total of 48 single nucleotide polymorphisms (SNP) from 40 associated loci were typed in a cohort of 208 SLE patients and 152 controls from Rheumatology Units of the University Hospital of Pisa (Italy) and University of P,cs Medical Center (Hungary). Regression analyses were performed to detect disease susceptibility loci and to identify genes affecting specific disease manifestations (renal, neurological, or skin involvement; arthritis; secondary Sjogren syndrome; and secondary antiphospholipid syndrome). Association of previously described risk alleles from HLA locus has been replicated, while IRF5, BLK, ITGAM, and IRF8 loci have been found to be consistent with previous published results. In addition, two new subphenotype-specific associations have been detected: SNP rs5754217 (UBE2L3) with skin involvement and rs3093030 (ICAM1-ICAM4-ICAM5) with hematological disorders. Overall, results from GAPAID project are consistent with previously established associations for HLA, IRF5, BLK, ITGAM, and IRF8 SLE susceptibility loci and report for the first time two subphenotype-specific associations.
引用
收藏
页码:1161 / 1168
页数:8
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