TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency.
OBJECTIVE
An altered production of cytokines underlies inflammatory bowel disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNFalpha gene promoters control cytokine production levels. The influence of these polymorphisms on susceptibility to ulcerative colitis (UC) and Crohn's disease (CD) and their association with clinical features were analyzed.


METHODS
Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A, -812 C/T, and -592 C/A) were determined using the LightCycler system with hybridization probes matched with one sequence variant. The study population included 99 UC patients, 146 CD patients, and 343 matched controls.


RESULTS
We did not find association between TNFalpha or IL-10 gene polymorphisms and UC or CD susceptibility, though a slight influence of -1082*G allele in UC appearance was observed. In a stratified analysis, a highly significant association between the -1082 AA IL-10 genotype and the steroid dependency was observed in IBD (p < 0.0001), contributing both UC (p = 0.004) and CD (p = 0.003) to this association. In contrast, TNFalpha genotypes did not influence steroid dependency in IBD. Further, the contribution of cytokine genotypes and of clinical features to the appearance of steroid-dependent status (dependent variable) was studied by multivariate analysis. The steroid-dependent phenotype correlated in UC with extensive disease (p = 0.010) and with the low producer -1082 AA IL-10 genotype (p = 0.002) and in CD with penetrating disease (p = 0.010), arthritis (p = 0.011), and the -1082 AA IL-10 genotype (p = 0.006).


CONCLUSIONS
The main conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a relevant risk factor for developing steroid-dependent IBD.
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Patricia
P
Castro-Santos
Ana
A
Suarez
Laureano
L
López-Rivas
Lourdes
L
Mozo
Carmen
C
Gutierrez
D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D013256:Steroids / Q000009:adverse effects; D019966:Substance-Related Disorders / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10