Investigative ophthalmology & visual science · 2007
Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Matsuda Akira, Ebihara Nobuyuki, Kumagai Naoki, Fukuda Ken, Ebe Koji, Hirano Koji, Sotozono Chie, Tei Mamoru, Hasegawa Koichi, Shimizu Makiko, Tamari Mayumi, Namba Kenichi, Ohno Shigeaki, Mizuki Nobuhisa, Ikezawa Zenro, Shirakawa Taro, Hamuro Junji, Kinoshita Shigeru
Аннотация
PURPOSE: Previous reports have shown genetic predisposition for atopic dermatitis (AD). Some of the severe complications of AD manifest in the eye, such as cataract, retinal detachment, and keratoconjunctivitis. This study was conducted to examine the genetic association between the atopy-related genes and patients with ocular complications (ocular AD).
METHODS: Seventy-eighty patients with ocular AD and 282 healthy control subjects were enrolled in an investigation of the association between the atopy-related genes (FCERB, IL13, and IFNGR1) and ocular AD. Genetic association studies and functional analysis of single nucleotide polymorphisms (SNPs) were performed.
RESULTS: The -56TT genotype in the IFNGR1 promoter region was significantly associated with an increased risk of ocular AD under recessive models (chi(2) test, raw P = 0.0004, odds ratio 2.57). The -56TT genotype was more common in atopic cataracts. A reporter gene assay showed that, after stimulation with IFN-gamma, the IFNGR1 gene promoter construct that contained the -56T allele, a common allele in ocular AD patients, manifested higher transcriptional activity in lens epithelial cells (LECs) than did the construct with the -56C allele. Real-time PCR analysis demonstrated higher IFNGR1 mRNA expression in the LECs in atopic than in senile cataracts. iNOS expression by IFNGR1-overexpressing LECs was enhanced on stimulation with IFN-gamma and LPS.
CONCLUSIONS: The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts.
METHODS: Seventy-eighty patients with ocular AD and 282 healthy control subjects were enrolled in an investigation of the association between the atopy-related genes (FCERB, IL13, and IFNGR1) and ocular AD. Genetic association studies and functional analysis of single nucleotide polymorphisms (SNPs) were performed.
RESULTS: The -56TT genotype in the IFNGR1 promoter region was significantly associated with an increased risk of ocular AD under recessive models (chi(2) test, raw P = 0.0004, odds ratio 2.57). The -56TT genotype was more common in atopic cataracts. A reporter gene assay showed that, after stimulation with IFN-gamma, the IFNGR1 gene promoter construct that contained the -56T allele, a common allele in ocular AD patients, manifested higher transcriptional activity in lens epithelial cells (LECs) than did the construct with the -56C allele. Real-time PCR analysis demonstrated higher IFNGR1 mRNA expression in the LECs in atopic than in senile cataracts. iNOS expression by IFNGR1-overexpressing LECs was enhanced on stimulation with IFN-gamma and LPS.
CONCLUSIONS: The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts.
Предметные рубрики MeSH
AdolescentAdultAgedCataractChildDermatitis, AtopicEpithelial CellsFemaleFluorescent Antibody Technique, IndirectGenetic TestingGenotypeHumansLens, CrystallineMaleMiddle AgedNitric Oxide Synthase Type IIPolymorphism, Single NucleotidePromoter Regions, GeneticRNA, MessengerReceptors, InterferonReverse Transcriptase Polymerase Chain ReactionRisk FactorsTranscription, GeneticInterferon gamma Receptor