Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Ethnic Specific Genetic Associations within the FCRL Gene Cluster in SLE.

Pajewski15,  Nickolas M., Langefeld23,  Carl D., Kaufman11,  Kenneth M., Williams23,  Adrienne, Comeau23,  Mary, Alarcon2,  Graciela S., Petri1,  Michelle A.

Timonium, MD
Oklahoma Medical Research Foundation, Uppsala, Sweden
Oklahoma Medical Research Foundation; The University of Oklahoma Health Sciences Center; Oklahoma City VA Medical Center
Pediatrics, U. of Washington, Seattle, WA
UCLA School of Medicine, Los Angeles, CA
UCSF-Box 0500, San Francisco, CA
Univ Alabama Birmingham
Univ of OK Hlth Sci Ctr, Oklahoma City, OK
Univ of PuertoRico Schl of Med, San Juan, PR
Univ Texas Health Sci Ctr, Houston, TX
Universidad del Rosario, Colombia
Oakland, CA
University of Chicago, Chicago, IL
University of Colorado-Denver SOM, Aurora, CO
USC School of Medicine, Los Angeles, CA
Wake Forest University Health Sciences
Hanyang Univ Medical Center, Seoul, Korea, Republic of
Imperial College London
Med Univ of South Carolina, Charleston, SC
N Shore Univ Hosp Rsch Ctr, Manhasset, NY
Northwestern University, Chicago, IL
Oklahoma Med Res Foundation, Oklahoma City, OK
Oklahoma Med Research Foundation, Oklahoma City, OK

Background:

The FCRL gene cluster in humans on chromosome 1q23.1 encodes 5 proteins that share a common ancestor with the classical Ig-binding Fc receptors. Each of the FCRL1–5 gene products are expressed by B cells but vary in their distribution on different subpopulations while FCRL3 is also found on NK and T cell subsets. Despite the similarity to the classical FCR, no definitive data demonstrate binding of Ig but very recent studies suggest binding of MHC and MHC-like molecules. A functional promoter variant in the FCRL3 locus has been inconsistently associated with SLE.

Methods:

We have performed a large case-control association study (n= (cases:controls) 3938:3491/1527:1811/961:336/1265:1260 European-American (EA)/African-American (AA)/Hispanic (Hisp)/Asian) with 123 SNPs that span 5 FCRL genes (FCRL1–5) on chrm 1q23.1. SNPs were selected from variants identified in a re-sequencing project and were genotyped on a custom iSelect array (Illumina) as part of a large SLEGEN consortium experiment. Logistic regression models were used to test for association adjusting for population structure through principal components analysis and gender.

Results:

In the Korean population (cases=640; controls=740), we detected association within the FCRL5 gene with strongest association at rs1571967 (intronic SNP)(p=3.6×10-4, OR=0.61[0.47–0.80]). This SNP was replicated in an independent collection of Asian case/control samples from North America (n=625/520) (combined p=3.6×10-5, OR=0.66 [0.54–0.80]).

We also observed independent association at 2 non-synonymous SNPs in the FCRL5 gene in the Asian population (peak association at rs6679793, combined p=2.0×10-4, OR=0.69 [57–0.84]). No evidence of association within FCRL3 (including the previously associated -169 promoter SNP, rs7528684) was observed. No significant associations (p<0.005) were detected in the FCRL1–5 genes in the EA, AA and Hisp populations.

Conclusions:

Together, these results demonstrate an association in the FCRL5 gene with SLE in Asians. FCRL5 is known to bind a viral MHC class I-like molecule and is likely to be involved in regulating innate immunity. The identification of non-synonymous SNPs in FCRL5 that associate with SLE in Asian populations provides the opportunity to explore the impact of genetic variation in regulating immune responses in autoimmunity.

To cite this abstract, please use the following information:
Pajewski, Nickolas M., Langefeld, Carl D., Kaufman, Kenneth M., Williams, Adrienne, Comeau, Mary, Alarcon, Graciela S., et al; Ethnic Specific Genetic Associations within the FCRL Gene Cluster in SLE. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1591
DOI: 10.1002/art.29357

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