Polymorphism of IFN-gamma gene and Vogt-Koyanagi-Harada disease.
OBJECTIVE
Interferon-gamma (IFN-gamma) is a key cytokine in inflammatory disorders. Elevated aqueous and serum levels of IFN-gamma levels have been reported to be elevated in patients with Vogt-Koyanagi-Harada (VKH) disease. The aim of this study was to determine the IFN-gamma gene polymorphisms in VKH disease.


METHODS
The study involved 136 VKH patients and 176 healthy controls, who were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) and functional microsatellite (CA) repeats (rs3138557) in the first intron of the IFN-gamma gene. Moreover, clinical manifestations of the patients were also analyzed.


RESULTS
Diffuse choroiditis/staining of fluorescein angiography was seen in all VKH patients in this study. Sunset glow fundus and nummular chorioretinal depigmented scars were observed in 83.9%, and 36.1% of the patients, respectively. Neurological and auditory disorders were observed in 90.1% of the patients: meningismus (79.8%), tinnitus (53.0%), and cerebrospinal fluid pleocytosis (70.0%). Dermatologic manifestations were observed in 22.9% of the patients, manifesting as alopecia (6.9%), poliosis (17.6%), and vitiligo (13.0%). In addition, 22.1% of the patients were classified as having complete VKH disease, while 65.4% as having incomplete VKH disease, and 12.5% as having probable VKH disease. There were no significant differences in the allele and genotype frequencies between VKH patients and healthy controls. In addition, we found no association between each clinical manifestation and SNP (re2430561) in the healthy control subject. A strong linkage disequilibrium (LD) was found in the functional SNP T allele and functional microsatellite 12 (CA) repeats (D'=0.96-0.99).


CONCLUSIONS
The functional SNP T allele and microsatellite 12 (CA) repeats were found to have a strong LD, although a genetic susceptibility for the IFN-gamma gene could not be demonstrated among the Japanese VKH patients.
Horie
Yukihiro
Y
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Japan. y-horie@med.hokudai.ac.jp
Kitaichi
Nobuyoshi
N
Takemoto
Yuko
Y
Namba
Kenichi
K
Yoshida
Kazuhiko
K
Hirose
Shigeto
S
Hasumi
Yukiko
Y
Ota
Masao
M
Inoko
Hidetoshi
H
Mizuki
Nobuhisa
N
Ohno
Shigeaki
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics*
D007371:Interferon-gamma