No association or linkage to IDDM of an interferon regulatory factor-1 gene polymorphism in a Danish population. The Danish Study Group for Diabetes in Childhood.
Nitric oxide is a potent mediator of the cytokine-induced cytotoxic effect on pancreatic beta cells. It has been shown that the inducible nitric oxide synthase (iNOS) is induced in islets of Langerhans by interleukin-1 beta (IL-1 beta). Interferon regulatory factor-1 (IRF-1), a transcriptional factor known to play an essential role in the induction of the inducible nitric oxide synthase, has also been shown to be induced by IL-1 beta in isolated islets of Langerhans. In the present study we analysed a GT nucleotide repeat polymorphism in the intron 7 of the IRF-1 gene. We typed 123 Danish Caucasian insulin-dependent diabetes mellitus (IDDM) multiplex families (550 individuals including 271 diabetic patients) and 108 control subjects of Danish Caucasian origin. In total, seven alleles were identified. No significant differences in either allele or genotype distribution were found comparing IDDM patients with control subjects (P = 0.7 and P = 0.5, respectively). An extended transmission disequilibrium test (ETDT) did not reveal transmission disequilibrium in an allele-wise manner. A 16-nucleotide deletion was found when sequencing the region containing the polymorphic GT repeat. This new deletion was in linkage disequilibrium with the GT-repeat polymorphism, as it was only seen with alleles of more than 13 GT tandem repeats. No association with IDDM for the deletion was observed. Furthermore, three single base substitutions linked to the 16 nucleotide deletion were identified. Even though we could not associate the GT-repeat polymorphism to IDDM in this study, additional mutation screening is warranted, as we still think the IRF-1 gene is a potential candidate gene for IDDM.
Johannesen
J
J
Steno Diabetes Centre, Gentofte, Denmark.
Karlsen
A E
AE
Nerup
J
J
Pociot
F
F
D000483:Alleles; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D018900:Dinucleotide Repeats / Q000235:genetics*; D005787:Gene Frequency; D005809:Genes, Regulator / Q000276:immunology; D005838:Genotype; D006801:Humans; D050856:Interferon Regulatory Factor-1; D015810:Linkage Disequilibrium; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins