IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65 antibody in Graves' disease.
OBJECTIVE
This study aimed to investigate whether interleukin-18 (IL-18) gene polymorphisms are associated with the development of antibody against the 65-kDa isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients with Graves' disease.


METHODS
A total of 398 unrelated Japanese patients with Graves' disease, with and without GAD65Ab, were recruited. Three single nucleotide polymorphisms in the IL-18 gene were examined and the polymorphic allele and the genotype and haplotype frequencies calculated.


RESULTS
The frequency of the GG genotype at position -4675 of the IL-18 gene was significantly lower in Graves' disease patients with GAD65Ab than those without (4% vs. 24%, P = 0.0126). The -4675C allele frequency was significantly greater in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The homozygous -4675G/-607A/-137G haplotype was less common in Graves' disease patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144).


CONCLUSIONS
These findings in a Japanese population indicate that Graves' disease patients carrying the GG genotype at position -4657 of the promoter of the IL-18 gene or a gene in linkage disequilibrium with the -4675G/-607A/-137G haplotype have a low risk for the development of GAD65Ab in Graves' disease.
Hiromatsu
Y
Y
Department of Endocrinology and Metabolism, Kurume University School of Medicine, Fukuoka, Japan. yuji@med.kurume-u.ac.jp
Mukai
T
T
Kaku
H
H
Miyake
I
I
Ichimura
M
M
Fukutani
T
T
Nakayama
H
H
Takata
K
K
Imamura
Y
Y
Shoji
S
S
Yamada
K
K
Koda
Y
Y
Bednarczuk
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D006111:Graves Disease / Q000150:complications / Q000235:genetics* / Q000276:immunology; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology
D000906:Antibodies; D020382:Interleukin-18; C505804:GAD55, human; D005968:Glutamate Decarboxylase