RESEARCH - Gene interaction suggests novel pathway for B-cell signaling in SLE

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Gene Interaction Suggests Novel Pathway for B-Cell Signaling in

Systemic Lupus Erythematosus

Jacquelyn K. Beals, PhD

November 10, 2009 (Honolulu, Hawaii) — An international research team

seeking genes that affect susceptibility to systemic lupus

erythematosus (SLE) through interactions with BANK1 has identified 2

protein–protein interactions that might represent a previously unknown

B-cell signaling pathway. The pathway might be regulated by type I

interferon (IFN)-α and is likely to influence B-cell response to

autoantigens in SLE.

The BANK1 gene encodes a B-cell scaffold protein with ankyrin repeats

— repeating sequences of 33 amino acids that fold into structures

involved in molecular recognition through protein–protein

interactions. The association of a BANK1 variant with SLE was first

demonstrated in 2008 in a Swedish genome-wide association study

(GWAS). This association was validated in 3 independent European

datasets and replicated in European-American and Chinese populations.

The goal of the new study, presented here at the American Society of

Human Genetics (ASHG) 59th Annual Meeting by Angélica A.

Delgado-Vega, MD, MSc, Department of Genetics and Pathology, Rudbeck

Laboratory, Uppsala University, Sweden, was to identify genes that

influence SLE susceptibility through their genetic interaction with

BANK1. Another goal was to determine if the interaction could explain

larger risk factors.

The initial GWAS scan for genetic interactions included 256 SLE cases

and 515 controls. Independent replication studies involved

European-Americans (676 cases, 850 controls) and Europeans (1265 cases

and 1506 controls). Statistical analyses of all possible interactions

between genotype pairs determined that BANK1 interacted with 29 genes.

Among these were BLK, coding for B-cell tyrosine kinase, and ITPR2,

for inositol 1,4,5-triphosphate receptor 2.

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Read the full article here:

http://www.medscape.com/viewarticle/712085

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