TY - JOUR
T1 - A polymorphism in the promoter region of the gene for interleukin-6 is associated with susceptibility to type 1 diabetes mellitus
AU - Jahromi, Mohamed
AU - Millward, B. A.
AU - Demaine, A. G.
PY - 2000/10/26
Y1 - 2000/10/26
N2 - Type 1 diabetes mellitus is an autoimmune disease characterized by the destruction of the insulin-producing islet β cells. It is likely that several genetic and environmental factors contribute to this process. There is increasing evidence showing that polymorphisms in cytokine genes may play an important role in modifying the immune response. Interleukin-6 (IL-6) is a cytokine that has been implicated in a number of immune-mediated diseases. Further, there is a polymorphism at position -174 (G(-174)C) of the promoter region of the IL-6 gene that may alter the expression of the gene. In this study, the G(- 174)C polymorphism was investigated in 257 Caucasoid patients with type 1 diabetes, 53 two-parent-proband trios, and 120 normal, healthy controls. DNA was amplified using amplimers that flank the G(-174)C site, and the products were digested with the restriction endonuclease NlaIII to detect the G or the C allele. The homozygous G,G(-174) genotype was increased in the patients compared with the normal controls (50.6% vs. 33.3%, p < 0.002), with a decrease in the C,C genotype in the patients compared with the controls (12.5% vs. 24.2%, respectively, p < 0.004). In the 53 trios studied, the G allele was transmitted in 29 of 53 informative meioses. There was no association with age at onset of diabetes or the presence of diabetic complications. In conclusion, these results suggest that the IL-6 gene may contribute to the genetic susceptibility to type 1 diabetes.
AB - Type 1 diabetes mellitus is an autoimmune disease characterized by the destruction of the insulin-producing islet β cells. It is likely that several genetic and environmental factors contribute to this process. There is increasing evidence showing that polymorphisms in cytokine genes may play an important role in modifying the immune response. Interleukin-6 (IL-6) is a cytokine that has been implicated in a number of immune-mediated diseases. Further, there is a polymorphism at position -174 (G(-174)C) of the promoter region of the IL-6 gene that may alter the expression of the gene. In this study, the G(- 174)C polymorphism was investigated in 257 Caucasoid patients with type 1 diabetes, 53 two-parent-proband trios, and 120 normal, healthy controls. DNA was amplified using amplimers that flank the G(-174)C site, and the products were digested with the restriction endonuclease NlaIII to detect the G or the C allele. The homozygous G,G(-174) genotype was increased in the patients compared with the normal controls (50.6% vs. 33.3%, p < 0.002), with a decrease in the C,C genotype in the patients compared with the controls (12.5% vs. 24.2%, respectively, p < 0.004). In the 53 trios studied, the G allele was transmitted in 29 of 53 informative meioses. There was no association with age at onset of diabetes or the presence of diabetic complications. In conclusion, these results suggest that the IL-6 gene may contribute to the genetic susceptibility to type 1 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=0033780153&partnerID=8YFLogxK
U2 - 10.1089/10799900050163253
DO - 10.1089/10799900050163253
M3 - Article
C2 - 11054276
AN - SCOPUS:0033780153
VL - 20
SP - 885
EP - 888
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 10
ER -