Systemic Lupus Erythematosus

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Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus

  1. Elena Sanchez1,
  2. Ryan D. Webb2,
  3. Astrid Rasmussen1,
  4. Jennifer A. Kelly1,
  5. Laura Riba3,
  6. Kenneth M. Kaufman4,
  7. Ignacio Garcia-de la Torre5,
  8. Jose F. Moctezuma6,
  9. Marco A. Maradiaga-Ceceña7,
  10. Mario H. Cardiel-Rios8,
  11. Eduardo Acevedo9,
  12. Mariano Cucho-Venegas9,
  13. Mercedes A. Garcia10,
  14. Susana Gamron11,
  15. Bernardo A. Pons-Estel12,
  16. Carlos Vasconcelos13,†,
  17. Javier Martin14,
  18. Teresa Tusié-Luna3,
  19. John B. Harley15,‡,
  20. Bruce Richardson16,
  21. Amr H. Sawalha4,§,
  22. Marta E. Alarcón-Riquelme17,§,*

Article first published online: 30 NOV 2010

DOI: 10.1002/art.27753

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 62, Issue 12, pages 3722–3729, December 2010

Additional Information

How to Cite

Sanchez, E., Webb, R. D., Rasmussen, A., Kelly, J. A., Riba, L., Kaufman, K. M., Garcia-de la Torre, I., Moctezuma, J. F., Maradiaga-Ceceña, M. A., Cardiel-Rios, M. H., Acevedo, E., Cucho-Venegas, M., Garcia, M. A., Gamron, S., Pons-Estel, B. A., Vasconcelos, C., Martin, J., Tusié-Luna, T., Harley, J. B., Richardson, B., Sawalha, A. H. and Alarcón-Riquelme, M. E. (2010), Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis & Rheumatism, 62: 3722–3729. doi: 10.1002/art.27753

Author Information

  1. 1

    Oklahoma Medical Research Foundation, Oklahoma City

  2. 2

    University of Oklahoma Health Sciences Center, Oklahoma City

  3. 3

    Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

  4. 4

    Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and VAMC, Oklahoma City

  5. 5

    Hospital General de Occidente, Zapopan, Mexico

  6. 6

    Hospital General de México, Mexico City, Mexico

  7. 7

    Hospital General de Culiacán, Culiacan, Mexico

  8. 8

    Hospital General Dr. Miguel Silva, Morelia, Mexico

  9. 9

    Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru

  10. 10

    Hospital Interzonal General de Agudos “General San Martín,” La Plata, Argentina

  11. 11

    Hospital Nacional de Clínicas, Universidad Nacional de Córdoba, Cordoba, Argentina

  12. 12

    Sanatorio Parque, Rosario, Argentina

  13. 13

    Hospital Santo Antonio, Unidade Multidisciplinar em Investigação Biomédica/Instituto de Ciências Biomédicas de Abel Salazar, Porto, Portugal

  14. 14

    Instituto de Biomedicina y Parasitología López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain

  15. 15

    Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

  16. 16

    University of Michigan and VAMC, Ann Arbor

  17. 17

    Pfizer–Universidad de Granada–Junta de Andalucía, Granada, Spain and Oklahoma Medical Research Foundation, Oklahoma City

  1. †

    Dr. Vasconcelos has received consulting fees, speaking fees, and/or honoraria from Merck, Sharp, and Dohme and Roche (less than $10,000 each).

  2. ‡

    Dr. Harley has received consulting fees, speaking fees, and/or honoraria from Biorad Labs, Immunovision, and IVAX Diagnostics (more than $10,000 each) and owns stock in IVAX Diagnostics.

  3. §

    Drs. Sawalha and Alarcón-Riquelme contributed equally to this work.

*Oklahoma Medical Research Foundation, 825 NE 13th Street, MS #24, Oklahoma City, OK 73104

Publication History

  1. Issue published online: 30 NOV 2010
  2. Article first published online: 30 NOV 2010
  3. Accepted manuscript online: 16 SEP 2010 01:37PM EST
  4. Manuscript Accepted: 9 SEP 2010
  5. Manuscript Received: 20 APR 2010

Funded by

  • NIH grants from the National Institute of Allergy and Infectious Diseases. Grant Numbers: R03-AI-076729, P20-RR-020143, P30-AR-053483
  • Lupus Foundation of America
  • University of Oklahoma Health Sciences Center
  • Oklahoma City VAMC
  • Oklahoma Medical Research Foundation
  • NIH. Grant Numbers: AR-062277, AR-042460, AI-024717, AI-083194, RR-020143
  • Swedish International Development Agency
  • Swedish Research Council for Medicine
  • Instituto de Salud Carlos III
  • NIH grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (American Recovery and Reinvestment Act). Grant Numbers: AR-058621, CA-141700, AI-083194

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Abstract

Objective

To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE).

Methods

Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression.

Results

A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele.

Conclusion

Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.

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