NF[kappa]B and Its Inhibitor I[kappa]B in Relation to Type 2 Diabetes and Its Microvascular and Atherosclerotic Complications

Nuclear factor [kappa] B (NF[kappa]B) is an important transcription factor that together with its inhibitor (I[kappa]B) participates in the activation of genes involved in immune responses. We examined the CA repeat polymorphism of the NFKB1 gene (encoding for NF[kappa]B) and A/G point variation in the 3UTR region of the nuclear factor kappa B inhibitor alpha (NFKBIA) gene (encoding for I[kappa]B) in Czech and German patients with type 2 diabetes. The sample consisted of 211 patients, both with and without kidney complications, and 159 controls. Additionally, 152 patients with systemic lupus erythematosus (SLE) were genotyped for NFKBIA polymorphism. We observed a significant increase in the homozygous AA genotype of the NFKBIA gene when compared with the control group (the highest value was in diabetics without diabetic nephropathy [p sub(c)* = 0.0015, odds ratio = 3.59]). No differences were seen between the SLE and control groups. With regard to the polymorphism of the NFKB1 gene, we did not observe any significant differences between the groups. Since the AA genotype of the NFKBIA gene presents a risk for type 2 diabetes development but not for diabetic nephropathy alone, we believe that the NF[kappa]B gene polymorphism can influence the pathogenesis of diabetes mellitus and affect its complications. Negative findings relative to other inflammatory autoimmune diseases, such as SLE, suggest a specific relationship between NF[kappa]B and type 2 diabetes mellitus.