Alleles of the IL12B 3'UTR associate with late onset of type 1 diabetes.
Carriage of a polymorphism in the 3'untranslated region of the IL12B gene encoding IL-12p40 was investigated in subjects with type 1 diabetes mellitus stratified by age at diagnosis (n = 648) and compared with a population-based control cohort (n = 246) residing in Western Australia. DNA samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism or pyrosequencing. The C allele was more common in patients diagnosed after age 16 years than in controls (29% vs 17%, OR = 2.0, 95% CI = 1.4-2.7, p = 0.00003) or than in patients diagnosed when younger age 16 years (29% vs 22%, OR = 1.4, 95% CI = 1.1-1.9, p = 0.01). This reflected increases in homozygous and heterozygous carriage of the C allele. Heterozygosity was associated with a delayed disease in the late-onset diabetics (p = 0.005; Student's t-test). The effects of IL12B 3'untranslated region alleles on type 1 diabetes mellitus may reflect different levels of p40 available to form p40 homodimer, IL-12 (p35p40), and IL-23 (p19p40).
Windsor
Lydia
L
School of Surgery and Pathology, University of Western Australia; Nedlands, Australia.
Morahan
Grant
G
Huang
Dexing
D
McCann
Vincent
V
Jones
Timothy
T
James
Ian
I
Christiansen
Frank T
FT
Price
Patricia
P
D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018076:DNA, Complementary / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D008875:Middle Aged; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000235:genetics*; D014904:Western Australia
D020413:3' Untranslated Regions; D018076:DNA, Complementary; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12