Lack of Association of a Functional –94ins/delATTG NFKB1 Promoter Polymorphism with Susceptibility and Clinical Expression of Biopsy-Proven Giant Cell Arteritis in Northwest Spain

JAVIER MARTIN, CRISTINA PEREZ-ARMENGOL, JOSE A. MIRANDA-FILLOY, JOSE R. VILCHEZ, MIGUEL A. LOPEZ-NEVOT, CARLOS GARCIA-PORRUA, and MIGUEL A. GONZALEZ-GAY

ABSTRACT.

Objective. Giant cell arteritis (GCA) is a vasculitis preferentially involving large and middle-sized arteries in the elderly. The nuclear factor of k-light polypeptide gene enhancer in B cells (NF-kB) is a family of 5 proteins expressed in most cells that function to regulate gene transcription. NFKB1 gene plays a critical role in the coordination of the immune system by regulating the transcription of a broad variety of genes implicated in the immune response. A NFKB1 promoter polymorphism consisting of a common insertion/deletion (–94ins/delATTG) located between 2 putative key promoter regulatory elements and showing functional effects on the transcription of the NFKB1 gene has been described. Since GCA is a polygenic disease, we sought to assess the potential role of the –94ins/delATTG NFKB1 promoter polymorphism in susceptibility to GCA and to determine if this polymorphism is implicated in the clinical expression of this vasculitis.

Methods. Ninety-six patients with biopsy-proven GCA and 204 ethnically matched Caucasian controls from the Lugo region (Northwest Spain) were studied. Genotyping of the –94ins/delATTG NFKB1 promoter polymorphism was performed by fluorescent polymerase chain reaction (PCR).

Results. No significant differences in allele or genotype frequencies for this NFKB1 promoter polymorphism were observed between patients with GCA and controls even when patients were stratified according to gender, presence of polymyalgia rheumatica (n = 38), severe ischemic manifestations (n = 49), or other clinical manifestations of GCA.

Conclusion. Our results do not support a role for –94ins/delATTG NFKB1 promoter polymorphism in susceptibility and clinical expression of GCA in a Northwestern Spanish population. (J Rheumatol 2006;33:285-8)

Key Indexing Terms:

GIANT CELL (TEMPORAL) ARTERITIS
SUSCEPTIBILITY
POLYMORPHISM
SEVERE ISCHEMIC MANIFESTATIONS
^_94INS/DELATTG NFKB1 PROMOTER

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From the Instituto de Parasitologia y Biomedicina Lopez-Neyra. CSIC; the Division of Immunology, Hospital Virgen de las Nieves, Granada; and the Division of Rheumatology, Hospital Xeral-Calde, Lugo, Spain.

J. Martin, MD, PhD; C. Perez-Armengol, PhD, Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC; J.R. Vilchez, PhD; M.A. Lopez-Nevot, MD, PhD, Servicio de Inmunología, Hospital Virgen de las Nieves; M.A Gonzalez-Gay, MD, PhD; J.A. Miranda-Filloy, MD; C. Garcia-Porrua, MD, PhD, Division of Rheumatology, Hospital Xeral-Calde.

Dr. Gonzalez-Gay and Dr. Martin share senior authorship of this report.

Address reprint requests to Dr. M.A. Gonzalez-Gay, Rheumatology Division, Hospital Xeral-Calde, c) Dr. Ochoa s/n, 27004, Lugo, Spain. E-mail: miguelaggay@hotmail.com

Accepted for publication October 10, 2005.

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