RESUMO
BACKGROUND: Type 1 diabetes (T1D) is a genetically conditioned autoimmune disease in which cytokines play an important role. Objectives. To check for the association of polymorphisms of cytokine genes with type 1 diabetes. Subjects. This work included 50 cases with T1D and 98 healthy individuals from the Nile Delta region of Egypt. Cases included 20 males and 30 females with a median age of 25 and range of 15-50 years. METHODS: DNA was amplified using PCR with sequence-specific primers for detection of polymorphisms related to tumor necrosis factor (TNF)-alpha(- 308) (G/A), interleukin (IL)-10(- 1082) (G/A), IL-6(- 174) (G/C), and IL-1Ra (VNTR). RESULTS: Cases with T1D showed significant higher frequency of genotypes of TNF-alpha(- 308) AA (p < 0.001, odds ratio (OR) = 7.91), IL-6-17CC (p < 0.05, OR = 3.36) and IL-1Ra A1A1 (p < 0.05, OR = 3.68) with significant lower frequencies of TNF-alpha(- 308) GA, and IL-1Ra A1A2 genotypes (p < 0.001 and < 0.05, respectively). They also showed significant higher frequency of TNF-alpha(- 308) allele A (p < 0.05, OR = 2.0), IL-1Ra allele A1 (p < 0.05, OR = 2.98) with a significant lower frequency of TNF-alpha(- 308) G allele and IL-1Ra A2 allele (p < 0.05). No significant difference was detected among cases in relation to IL-10(- 1082) (G/A) genotypes or alleles nor in relation to age, sex, consanguinity or family history of the disease. CONCLUSIONS: Polymorphisms related to TNF-alpha and IL-1Ra genes may be considered genetic markers for T1D among Egyptians with a potential impact on family counseling and management.
Assuntos
Doenças Autoimunes/genética , Diabetes Mellitus Tipo 1/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Egito , Feminino , Genótipo , Humanos , Interleucina-10/genética , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Interleukin (IL)-10 is a pluripotent cytokine with effects on numerous cell populations, in particular circulating and resident immune cells as well as epithelial cells. With its potent immunoregulatory capacities, its main biological function seems to be the limitation and termination of inflammatory responses. Hence, its low level expression found in psoriasis may have pathophysiological relevance to this immune disease. Remarkably, the induction of IL-10 expression was found by conventional antipsoriatic therapies, supporting the hypothesis that it may be a key cytokine in psoriasis. Furthermore, the first use in clinical trials in patients with established psoriasis showed that it had moderate antipsoriatic effects and was well tolerated. Moreover, long-term application in psoriatic patients in remission showed that it decreases the incidence of relapse and prolongs the disease free interval. The IL-10 antipsoriatic activity is suggested to be due to the effects on different cell populations, including antigen presenting cells and T-cells (type 1 / type 2 balance shift), but not through direct effects on keratinocytes. In conclusion, IL-10 seems to have major clinical and therapeutic implications in psoriasis. Further multicenter, placebo-controlled, double blind trials are required to be an established antipsoriatic therapy. We can come to the conclusion that IL-10 genetic polymorphism and expression is potentially a key immune marker in psoriasis.