APRIL polymorphism and systemic lupus erythematosus (SLE) susceptibility
Y. H. Lee1, F. Ota2,3, X. Kim-Howard2,3, K. M. Kaufman2 and S. K. Nath2,3
Objective. Two novel non-synonymous polymorphisms of the APRIL gene, codon 67 (rs11552708) and 96 (rs3803800), wererecently identified and tested for disease association. The 67G allele was reported to be associated with systemic lupus erythematosus (SLE) in a Japanese population. The aim of the study is to investigate whether the APRIL polymorphism associated with susceptibility to SLE in a Japanese population is associated with the susceptibility to SLE in other ethnic groups. Methods. Three hundred and forty-eightSLE patients (204 European-American, 103 African-American and 41 Hispanic) and 345 ethnicitymatched controls (201 European-American, 104 African-American and 40 Hispanic) were included from the Lupus Multiplex Registry and Repository (LMRR) and evaluated for genetic association. The APRIL codon 67 and codon 96 were genotyped by a 3-base extension method. Statistical evaluations were performedusing both chi-square and logistic regression analysis. Results. Both the single-nucleotide polymorphisms (SNPs) were in Hardy–Weinberg equilibrium in cases and controls within each ethnic group. The APRIL codon 67 was significantly associated with SLE risk under the dominant model adjusted by ethnicity (odds ratio, 95% confidence interval and P-values were 1.45 and 1.02–2.06 and 0.036,respectively). Race-specific analysis also showed a trend for association in African-American and Hispanic SLE subjects. Conclusion. The APRIL codon G67R polymorphism associated with SLE in a Japanese population may also be associated with SLE in other populations.
Systemic lupus erythematosus, APRIL, Polymorphisms.
Systemic lupus erythematosus (SLE) is the prototype of humanautoimmune diseases and a disorder of generalized autoimmunity. While the aetiology of SLE remains unclear, a strong genetic background is known to be important in the pathogenesis of SLE. APRIL (also known as a proliferation-inducing ligand, TNFSF13, TRDL-1, CD256 and TALL2) is a member of the tumour necrosis factor (TNF) superfamily and plays a role in immune responses and tumour cell growth .APRIL plays a regulatory role in B-cell proliferation by binding to B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI) on B cells . Serum APRIL levels are inversely associated with anti-dsDNA titre in SLE . B-lymphocyte stimulator (BlyS, BAFF) is a member of the TNF superfamily and is a potent B-cell co-stimulator and promotes B-cell differentiation,proliferation and survival . BLyS, like APRIL, binds to BCMA and TACI; and both belong to the TNF receptor super family and are mainly expressed in B-cells. Transgenic mice over expressing BlyS develop symptoms characteristic of SLE . It has been reported that APRIL affects the T-cell response  and the soluble decoy receptors for APRIL prolong the survival of lupus-prone NZBWF1 mice .These findings suggest that APRIL may be one of candidate genes involved in SLE. Interestingly, the APRIL gene is located on chromosome 17p13.1, a genomic location that has been known to be the linkage area in European-American families with vitiligo-related SLE
1 Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, College of Medicine, Korea University, Seoul,Korea, 2Arthritis and Immunology Research Program and 3Genetic Epidemiology Unit, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
and the hypothetical putative gene is known as SLEV1 . This linkage was supported by analysis in a separate population of European-American vitiligo multiplex families . Recently, Koyama et al.  identified two novel polymorphisms at the...