Genetic dissection of and XL9 region variants in Japanese patients with systemic lupus erythematosus: primary role for .

Objective: Major histocompatibility complex strongly contributes to susceptibility to systemic lupus erythematosus (SLE). In the European populations, and are susceptibility alleles, but locus was reported to account for the association of . With respect to , strong linkage disequilibrium with a variant rs2105898T in the XL9 region, located between and and regulates HLA-class II expression levels, was reported; however, the causative allele remains to be determined. Leveraging the genetic background of the Japanese population, where and are commonly present and only is associated with SLE, this study aimed to distinguish the genetic contribution of and XL9 variants.

Methods: Among the XL9 variants, two (rs2105898 and rs9271593) previously associated variants in the European populations and two (rs9271375 and rs9271378) which showed a trend towards association in a Japanese Genome-Wide Association Study were selected. Associations of the XL9 variants and were examined in 442 Japanese SLE patients and 779 controls. Genotyping of the XL9 variants was performed by TaqMan SNP Genotyping Assay and direct sequencing. alleles were determined by PCR-reverse sequence-specific oligonucleotide probes.

Results: Among the XL9 variants, associations of rs2105898T and rs9271593C were replicated in the Japanese population. However, these associations became no longer significant when conditioned on . In contrast, the association of remained significant after conditioning on the XL9 variants.

Conclusion: In the Japanese population, was found to be primarily associated with SLE, and to account for the apparent association of XL9 region.