Genetic and functional evaluation of an interleukin-12 polymorphism (IDDM18) in families with type 1 diabetes

• Published in: Journal of medical genetics Vol. 41; no. 4; p. e39
• Main Authors: Bergholdt, R, Ghandil, P, Johannesen, J, Kristiansen, O P, Kockum, I, Luthman, H, Rønningen, K S, Nerup, J, Julier, C, Pociot, F
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-04-2004; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Adult; affected sibling pairs; ASP; Basic Medicine; Child; Child, Preschool; Chromosomes; Cytokines; Deoxyribonucleic acid; Diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; DNA; Electronic Letter; Enzyme-Linked Immunosorbent Assay; Family Health; Genes; Genetic Predisposition to Disease; Humans; IDDM18; IL-12 production; Infant; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Interleukin-12 Subunit p40; Linkage Disequilibrium; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Polymorphism, Single Nucleotide; Protein Subunits - biosynthesis; Protein Subunits - genetics; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Studies; T1DM; TDT; type 1 diabetes mellitus
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2003.010454

Many cell types express the p35 chain, while the p40 subunit is expressed principally by activated macrophages and B cells. 2 The heterodimer, p70 or p75, is the biologically active IL-12. 13 IL12B is a candidate for IDDM18, as linkage disequilibrium is confined to a 30 kb region on chromosome 5, in which IL12B is the only known gene. 4 Several polymorphisms have been identified in IL12B, 2, 14 of which the A allele of a 3[variant prime]UTR (untranslated region) single nucleotide polymorphism (C1159A SNP) showed strong linkage disequilibrium with the T1DM susceptibility locus in Australian and British diabetes families. 4 Interestingly, evidence for functional significance of the 3[variant prime]UTR polymorphism was found by investigating Epstein-Barr virus (EBV) transformed cell lines. 4 A cell line with the genotype A/A showed significantly higher mRNA expression level than a C/C cell line. 4 In a recently undertaken Scandinavian T1DM genome scan no evidence for linkage to this region on chromosome 5 was demonstrated. 15 Confirmation of the significance of the IL12B 3[variant prime]UTR polymorphism in T1DM in other populations is important. [...]both the genetic and the functional data conflict with the original findings, and do not support the IL12B locus as a risk locus for T1DM.