Hiromatsu Y, Mukai T, Kaku H, Miyake I, Ichimura M, Fukutani T, Nakayama H, Takata K, Imamura Y, Shoji S, Yamada K, Koda Y, Bednarczuk T
Department of Endocrinology and Metabolism, Kurume University School of Medicine, Fukuoka, Japan.
Diabet Med. 2006 Feb;23(2):211-5. doi: 10.1111/j.1464-5491.2005.01734.x.
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.
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.
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).
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.
本研究旨在调查白细胞介素 - 18（IL - 18）基因多态性是否与格雷夫斯病患者中针对重组人谷氨酸脱羧酶65 kDa亚型（GAD65Ab）抗体的产生有关。
共招募了398名无亲缘关系的日本格雷夫斯病患者，其中有和没有GAD65Ab抗体的患者均包括在内。检测了IL - 18基因中的三个单核苷酸多态性，并计算了多态性等位基因、基因型和单倍型频率。
在患有GAD65Ab的格雷夫斯病患者中，IL - 18基因 - 4675位点的GG基因型频率显著低于未患该抗体的患者（4% 对24%，P = 0.0126）。携带GAD65Ab抗体的患者中 - 4675C等位基因频率显著高于未携带该抗体的患者（69% 对53%，P = 0.0168）。纯合的 - 4675G / - 607A / - 137G单倍型在患有GAD65Ab的格雷夫斯病患者中比未患该抗体的患者更少见（4% 对23%，P = 0.0144）。
在日本人群中的这些发现表明，携带IL - 18基因启动子 - 4657位点GG基因型或与 - 4675G / - 607A / - 137G单倍型处于连锁不平衡状态的基因的格雷夫斯病患者，在格雷夫斯病中发生GAD65Ab的风险较低。
