Original Contribution
The American Journal of Gastroenterology (2006) 101, 1039–1047; doi:10.1111/j.1572-0241.2006.00501.x
TNF
and IL-10 Gene Polymorphisms in Inflammatory Bowel Disease. Association of -1082 AA Low Producer IL-10 Genotype with Steroid Dependency
Patricia Castro-Santos BSc1, Ana Suarez PhD2, Laureano López-Rivas MD3, Lourdes Mozo PhD1 and Carmen Gutierrez MD, PhD1,2
- 1Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain
- 2Department of Functional Biology, University of Oviedo, Oviedo, Spain
- 3Department of Gastroenterology, Hospital San Agustín, Aviles, Spain
Correspondence: Carmen Gutierrez, Department of Immunology, Hospital Universitario Central de Asturias, c/ Julián Clavería s/n, 33006 Oviedo, Spain.
Received 2 August 2005; Accepted 20 November 2005.
Abstract
OBJECTIVES:
An altered production of cytokines underlies inflammatory bowel disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNF
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.
SUBJECTS AND METHODS:
Genetic polymorphisms of TNF (-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 TNF 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, TNF 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.
