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


CONCLUSIONS
The results suggest that individuals carrying specific genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.
Mehrian
R
R
University of Southern California School of Medicine, Los Angeles 90033, USA.
Quismorio
F P
FP
Strassmann
G
G
Stimmler
M M
MM
Horwitz
D A
DA
Kitridou
R C
RC
Gauderman
W J
WJ
Morrison
J
J
Brautbar
C
C
Jacob
C O
CO
D000069594:Abatacept; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D060908:CTLA-4 Antigen; D003627:Data Interpretation, Statistical; D053222:Fas Ligand Protein; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D016753:Interleukin-10 / Q000235:genetics* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D017058:Mexican Americans / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016753:Interleukin-10; D000069594:Abatacept