Our findings suggest evidence of a possible association between zinc and magnesium in the domestic drinking water and childhood diabetes in the far south-west of England. However, these possible protective effects of zinc and magnesium in domestic drinking water warrant further confirmation.
Type 1 diabetes mellitus is an autoimmune disease characterized by the destruction of the insulin-producing islet beta 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.
Nuclear factor kappa B (NFkappaB) is an important transcription factor that is involved in the response to oxidative stress and inflammation. Recent studies suggest that it may be involved in the development of diabetic microvascular complications. A highly polymorphic (CA) dinucleotide repeat microsatellite has been identified in the regulatory region of the NFkappaB gene. The aim of this study was to investigate whether this polymorphic region was associated with susceptibility to type 1 diabetes, or its late complications. Genomic DNA was extracted from the peripheral blood of 217 patients with type 1 diabetes mellitus (T1DM) and 111 normal healthy controls. In our population 18 alleles (A1-A18) were identified. There was a highly significant decrease in the frequency of allele 146 bp (A14) in type 1 diabetes (0.03) compared with the normal controls (0.28) (chi(2) = 79.8, Pc = 0.00001). In contrast, the frequency of the allele 138 bp (A10) was significantly increased in patients with type 1 diabetes (0.17) compared with the normal controls (0.02) (chi(2) = 32.8, P < 0.00000). These results demonstrate that the NFkappaB gene may play a role in the susceptibility to type 1 diabetes: individuals with the A10 allele may be more likely to develop diabetes compared with the A14 allele.
Summary The (MHC) class II association with insulin-dependent diabetes mellitus (IDDM) is well documented. However, it is likely that genes within the MHC class III and the class I region also play a role in determining susceptibility to IDDM. In this study we have used a novel molecular probe to investigate the class I P3A and P3B loci of 179 patients with IDDM and 142 normal control subjects. A highly significant increase in the frequency of the class I P3 4.0;1.5 kilobase (kb) and 4.0;1.8;1.5 kb genotypes was found in patients compared to the control subjects (22 46.8, 6 dr, p < 0.0001). The association with the P3B 1.5 kb allele was strongly associated with the age at onset of diabetes, being present in 96.2 % of subjects who developed diabetes between the age of 10-20 years compared to 55.0 and 74.6 % who developed diabetes before 10 years or after 20 years, respectively (2 2 31.4, p < 0.0001). There was no evidence for linkage disequilibrium between the DQA1 and DQB1 loci and P3B suggesting that this is an independent association. In conclusion, these results suggest that genes in both the MHC class I and II regions confer susceptibility to IDDM and are related to the age at onset of the disease. [Diabetologia (1995) 38: 623-628]
The majority of respondents supported the concept of medical screening in a dental setting and were willing both to have screening tests and discuss their results with the dental team. Patient acceptance is paramount for successful implementation of such screening programmes.
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