Genetic polymorphism of IL-12 p40 gene in immune-mediated disease

Abstract

Understanding of the genetic basis of autoimmune diseases is currently incomplete. Cytokine gene polymorphisms warrant consideration as factors explaining variation in the human immune and inflammatory responses and as candidate susceptibility genes for related pathological states. Interleukin 12 (IL-12) is a key regulator of the polarisation of immune responses to T helper 1 or 2 categories and plays a role in autoimmune and infectious diseases. Using a bioinformatic strategy, we aligned cDNA and expressed sequence tag sequences to identify putative polymorphic regions of the IL-12 p40 gene. Position 1188 in the 3' untranslated region (UTR) was polymorphic with the frequency of the common allele around 80% in healthy UK Caucasoids. PCR genotyping of multiple Caucasoid groups and an African group showed significant population variation. In a case-control design, the polymorphism was not associated with rheumatoid arthritis, Felty's syndrome or large granular lymphocyte syndrome with arthritis or multiple sclerosis. A nonsignificant increase in the B allele frequency was observed in the rare large granular lymphocyte syndrome without arthritis (odds ratio 2.02 95% CI 0.95-4.3). This new genetic marker could be useful in anthropological studies and should be investigated in other autoimmune, allergic, inflammatory and infectious diseases.

Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit

“…In particular, the 3ЈUTR alleles were found to be in Hardy-Weinberg equilibrium, with the TaqI− allele having a frequency of 0.82. Since this manuscript was in preparation, another group also found the 3ЈUTR TaqI polymorphism by comparing cDNA sequences; 15 they reported the frequency of the TaqI− allele as 0.8, which is similar to the frequency we observed. The TA repeat polymorphism in intron 4 showed a similar distribution, also in Hardy-Weinberg equilibrium.…”

Genetics of type 1 diabetes mellitus

“…211,212 Several polymorphisms have been identified in the IL 12B locus. 205,213 A 3ЈUTR (untranslated region) single base change showed strong linkage disequilibrium with the T1D susceptibility locus in Australian and British diabetes families, 29 but this observation needs to be replicated in other populations. 214 Other susceptibility loci A number of additional chromosomal regions demonstrating some evidence of linkage to T1D have been identified.…”

IL12B polymorphisms are linked but not associated with Plasmodium falciparum parasitemia: a familial study in Burkina Faso

“…Sequencing reaction was performed with the CEQ DTCS kit (Beckman Coulter, Fullerton, CA, USA) and a CEQ 8000 automated fluorescent sequencer (Beckman Coulter). In addition, IL12B 3 0 UTR polymorphism was determined by using an allele-specific restriction enzyme digestion method; 44 only the PCR product of the C allele contains a TaqI site. Digestion products were analyzed by electrophoresis on a 2% agarose gel stained by ethidium bromide.…”