Lack of association of IL-10 promoter gene variants with type 1 diabetes in a French population.
Although genetic predisposition to type 1 diabetes shows a strong association with human leukocyte antigen (HLA) class II alleles, additional genes may influence the immune process and the progression of beta cell loss. Preliminary reports suggested that IL-10 gene polymorphisms contribute to susceptibility to type 1 diabetes. We analyzed the frequencies of three main variants of the promoter region of the IL-10 gene at the positions -1082, -819, and -592 in a cohort of 358 type 1 diabetic patients representing the same regional population pattern and 519 controls from the same region using an enzyme-linked oligonucleotide sorbent assay. We did not find any statistical association in the entire cohort or after stratification for high-risk HLA-DQ alleles. However, the IL-10 -1082 polymorphism was significantly associated with GAD and IA-2 antibodies at clinical onset. Such polymorphism is known to be associated with the reduction of secreted IL-10 which may support the concept of accelerated Th-1 T-cell reactivity. In conclusion, IL-10 promoter gene variants may contribute, but to a minor extent, to disease susceptibility in juvenile type 1 diabetes and should not be included in the routine genetic screening of high-risk individuals.
Reynier
Frederic
F
HCL-bioMérieux Joint Unit, Edouard Herriot Hospital, 69347 Lyon, France.
Cazalis
Marie-Angelique
MA
Lecoq
Annick
A
Paye
Malick
M
Rosa
Audrey
A
Durand
Annie
A
Jhumka
Umar
U
Mougin
Bruno
B
Miossec
Pierre
P
Bendelac
Nathalie
N
Nicolino
Marc
M
Thivolet
Charles
C
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D044465:White People / Q000235:genetics*
D001323:Autoantibodies; C096322:ICA512 autoantibody; D016753:Interleukin-10; D005968:Glutamate Decarboxylase