Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus

Arthritis Rheum. 1998 Apr;41(4):596-602. doi: 10.1002/1529-0131(199804)41:4<596::AID-ART6>3.0.CO;2-2.


Objective: To determine whether genes participating in programmed cell death, including bcl-2, IL-10, Fas-L, and CTLA-4, may contribute to the genetic predisposition to systemic lupus erythematosus (SLE).

Methods: First, intragenic markers for the bcl-2, IL-10, Fas-L, and CTLA-4 genes were characterized and their extent of polymorphism in normal populations was determined. The allelic distribution of these gene markers in a large Mexican American SLE cohort of 158 patients and 223 ethnically matched controls was determined using fluorescent-labeled primers and semiautomated genotyping.

Results: The bcl-2, Fas-L, and IL-10 loci showed significantly different allelic distribution in SLE patients compared with controls, indicating an association between these genes and SLE. No association was found between SLE and the CTLA-4 gene. Further analysis revealed a synergistic effect between susceptibility alleles of the bcl-2 and IL-10 genes in determining disease susceptibility. Alone, the presence of each of these alleles was associated with a moderate increase in SLE risk, while the occurrence of these alleles together increased the odds of developing SLE by more than 40-fold.

Conclusion: The results suggest that individuals carrying specific genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Alleles
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Apoptosis / genetics
  • CTLA-4 Antigen
  • Data Interpretation, Statistical
  • Fas Ligand Protein
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunoconjugates*
  • Interleukin-10 / genetics*
  • Interleukin-10 / physiology
  • Lupus Erythematosus, Systemic / ethnology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Mexican Americans / genetics
  • Odds Ratio
  • Polymorphism, Genetic
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Repetitive Sequences, Nucleic Acid / genetics


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Immunoconjugates
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Interleukin-10
  • Abatacept