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.


Study of Systemic Lupus Erythematosus Susceptibility Genes in a Hispanic Population: Identification of Six New Candidate Susceptibility Loci.

Sanchez-Rodriguez1,  Elena, Kaufman3,  Kenneth M., Kelly1,  Jennifer A., Williams11,  Adrienne H., Ramos11,  Paula S., Rasmussen1,  Astrid, Jacob9,  Chaim O.

Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
US Department of Veterans Affairs Medical Center, Oklahoma City, OK and University of Oklahoma Health Sciences Center, Oklahoma City, OK
Wake Forest University Health Sciences, NC
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK and Center for Genomics and Oncological Research (GENyO), Granada, Spain
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK and US Department of Veterans Affairs Medical Center, Oklahoma City, OK
Imperial College London, Hammersmith Hospital, London, UK
Sanatorio Parque, Rosario, Argentina
University of Alabama, Birmingham, AL
University of California, Los Angeles, CA
University of California, San Francisco, CA
University of Southern California, Los Angeles, CA

Background:

Genome-wide association studies (GWAS) have proven highly effective for identifying hundreds of associations across numerous complex diseases. Four GWAS for systemic lupus erythematosus (SLE) in European populations and two in Asian populations have identified more than 20 robustly associated susceptibility genes. Differences in the prevalence and severity of SLE between various ethnicities are well documented, showing the need for further genetics studies in non-European populations.

Objective:

The aim of this study was to evaluate and replicate all genes previously associated with SLE with p values <0.05 in the SLEGEN1 study through fine mapping in Hispanic SLE cases and controls.

Material and Methods:

Here we evaluated 7069 single nucleotide polymorphisms (SNPs) in a set of 1510 Hispanic SLE patients and 825 Hispanic healthy controls. Tests of association were under a logistic regression model (SNPGWA), adjusting for ancestry proportions (ADMIXMAP) as covariates.

Results:

We confirmed 17 previously reported loci in European and Asian populations (BLK, IRF5, TNPO3, STAT4, ITGAM, ITGAX, 1q25, TNIP1, MSH5, HLA-DRA, XKR6, CFB, C2, MICB, PRDM1, ATG5 and LYN). In addition, we identified six new susceptibility loci in Hispanic SLE with a P< 0.0001 (C6orf10, MSRA, SLC44A4, ZBTB12, EHMT2 and CLIC1).

Conclusion:

While we replicated the majority of the previous GWAS genes, new candidate genes have been discovered. These findings support the need to perform GWAS and additional fine mapping in Hispanics to locate additional susceptibility loci.

1HarleyAlarcon-RiquelmeCriswell, JBMELA, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008;40:204–10.

To cite this abstract, please use the following information:
Sanchez-Rodriguez, Elena, Kaufman, Kenneth M., Kelly, Jennifer A., Williams, Adrienne H., Ramos, Paula S., Rasmussen, Astrid, et al; Study of Systemic Lupus Erythematosus Susceptibility Genes in a Hispanic Population: Identification of Six New Candidate Susceptibility Loci. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2148
DOI: 10.1002/art.29912

Abstract Supplement

Meeting Menu

2010 ACR/ARHP