BAT1 Promoter Polymorphism Is Associated with Rheumatoid Arthritis Susceptibility

ADOLFO QUIÑONES-LOMBRAÑA, ALEJANDRO LOPEZ-SOTO, FRANCISCO JAVIER BALLINA-GARCIA, MERCEDES ALPERI-LÓPEZ, RUBEN QUEIRO-SILVA, ANTONIO LOPEZ-VAZQUEZ, CARLOS LOPEZ-LARREA, and SEGUNDO GONZALEZ

ABSTRACT.

Objective. To analyze whether the polymorphisms -22 (G/C) and -348 (C/T) of the BAT1 gene are associated with susceptibility to rheumatoid arthritis (RA).

Methods. One hundred fifty-six patients with RA and 154 controls were genotyped for HLA-DRB1 and the polymorphisms -22 and -348 of the BAT1 gene.

Results. HLA-DRB1*04 alleles were associated with RA susceptibility (33.9% vs 20.1%; p_c = 0.04). Among these, HLA-DRB1*0401 (13.4% vs 5.1%; p_c = 0.04) and HLA-DRB1*0404 (5.7% vs 1.2%; p_c = 0.2) were increased in patients with RA. Additionally, carriage of BAT1 -348T polymorphism was strongly associated with RA (23.7% vs 12.1%; p_c = 0.0002). Significantly, BAT1 -348T was in linkage disequilibrium with HLA-DRB1*0404 and HLA-DRB1*0405. However, BAT1 -348 T was associated independently with HLA-DRB1 shared-epitope alleles (42.6% vs 18.9%; p = 0.001).

Conclusion. The BAT1 -348T polymorphism is associated with RA susceptibility independently of HLA-DRB1. The role of BAT1 in the regulation of tumor necrosis factor-a suggests that BAT1 may regulate the inflammatory response observed in patients with RA. (J Rheumatol First Release Mar 15 2008)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
MAJOR HISTOCOMPATIBILITY COMPLEX
HLA-DR
BAT1

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From the Department of Functional Biology, University of Oviedo, IUOPA; and Department of Rheumatology and Histocompatibility and Transplantation Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

Supported in part by grant FIS PI060841, from the Fondo de Investigaciones Sanitarias from the Spanish Ministry of Health. Mr. Lopez-Soto holds a predoctoral fellowship from FICYT of Asturias (ref. BP06-99).

A. Quiñones-Lombraña, BSc; A. Lopez-Soto, BSc; S. Gonzalez, MD, PhD, Department of Functional Biology, University of Oviedo; F.J. Ballina-Garcia, MD, PhD; M. Alperi-López, MD; R. Queiro-Silva, MD, PhD, Department of Rheumatology; A. Lopez-Vazquez, MD; C. Lopez-Larrea, PhD, Histocompatibility and Transplantation Unit, Hospital Universitario Central de Asturias, Fundación Renal "Iñigo Alvarez de Toledo".

Address reprint requests to Dr. S. González, Department of Functional Biology, IUOPA, Universidad de Oviedo, Facultad de Medicina, Julián Clavería sn, 33006, Oviedo, Spain. E-mail: segundog@uniovi.es

Accepted for publication December 3, 2007.