title: NFkappaB polymorphisms and susceptibility to type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Postgraduate Medical School, University of Plymouth, Plymouth PL6 8BX, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Hegazy
authors.forename: D A
authors.initials: DA
authors.lastname: O'Reilly
authors.forename: B M
authors.initials: BM
authors.lastname: Yang
authors.forename: A D
authors.initials: AD
authors.lastname: Hodgkinson
authors.forename: B A
authors.initials: BA
authors.lastname: Millward
authors.forename: A G
authors.initials: AG
authors.lastname: Demaine
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001345:Autoradiography; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics; D003930:Diabetic Retinopathy / Q000150:complications / Q000235:genetics; D018900:Dinucleotide Repeats / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: D016328:NF-kappa B