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IAN5 polymorphisms are associated with systemic lupus erythematosus

Department of Medicine, School of Medicine and Medical Sciences Research Institute, Eulji University, Daejeon, South Korea

DH Sheen

Department of Medicine, School of Medicine and Medical Sciences Research Institute, Eulji University, Daejeon, South Korea

SA Kim

Department of Pharmacology, School of Medicine and Medical Sciences Research Institute, Eulji University, Daejeon, South Korea

SK Won

Department of Medicine, School of Medicine and Medical Sciences Research Institute, Eulji University, Daejeon, South Korea

S-S Lee

Department of Medicine, Chonnam National University School of Medicine, Gwangju, Chonnam, South Korea

S-C Chae

Genome Research Center for Immune Disorders, Wonkwang University School of Medicine, Iksan, Chonbuk, South Korea

H-T Chung

Genome Research Center for Immune Disorders, Wonkwang University School of Medicine, Iksan, Chonbuk, South Korea

SC Shim

Department of Medicine, School of Medicine and Medical Sciences Research Institute, Eulji University, Daejeon, South Koreassc{at}eulji.ac.kr

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case–control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively), and –4432G > A SNP was associated with the development of leukopenia (P = 0.028) and the requirement of steroid pulse therapy (P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.

Key Words: biobreeding rat • immune-associated nucleotide 5 • single nucleotide polymorphism • systemic lupus erythematosus

Lupus, Vol. 18, No. 12, 1045-1052 (2009)
DOI: 10.1177/0961203309106830


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