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

Arthritis Rheum. 2010 Dec;62(12):3722-9. doi: 10.1002/art.27753.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • American Native Continental Ancestry Group / ethnology*
  • American Native Continental Ancestry Group / genetics*
  • CD11b Antigen / genetics
  • Case-Control Studies
  • Gene Frequency / genetics*
  • Genetic Predisposition to Disease / ethnology*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Interferon Regulatory Factors / genetics
  • Latin America
  • Linear Models
  • Lupus Erythematosus, Systemic / ethnology*
  • Lupus Erythematosus, Systemic / genetics*
  • OX40 Ligand / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • STAT4 Transcription Factor / genetics

Substances

  • CD11b Antigen
  • IRF5 protein, human
  • ITGAM protein, human
  • Interferon Regulatory Factors
  • OX40 Ligand
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • TNFSF4 protein, human

Grant support