Annals of clinical and translational neurology · 2020
Genetic factors for susceptibility to and manifestations of neuromyelitis optica.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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.
Matsushita Takuya, Masaki Katsuhisa, Isobe Noriko, Sato Shinya, Yamamoto Ken, Nakamura Yuri, Watanabe Mitsuru, Suenaga Toshihiko, Kira Jun-Ichi, Japan Multiple Sclerosis Genetic Consortium
Аннотация
OBJECTIVE: To identify genetic factors associated with susceptibility to and clinical features of neuromyelitis optica spectrum disorders (NMOSD).
METHODS: Genome-wide single nucleotide polymorphism (SNP) genotyping was conducted in 211 Japanese patients with NMOSD fulfilling the 2006 criteria with or without anti-aquaporin-4 (AQP4) antibody and 1,919 Japanese healthy controls (HCs). HLA-DRB1 and HLA-DPB1 alleles were genotyped in 184 NMOSD cases and 317 HCs. Multiple sclerosis (MS) risk alleles outside the major histocompatibility complex (MHC) region were tested in NMOSD and MS genetic burden (MSGB) scores were compared between HCs and NMOSD.
RESULTS: A SNP (rs1964995) in the MHC region was associated with NMOSD susceptibility (odds ratio (OR) = 2.33, P = 4.07 × 10-11 ). HLA-DRB1*08:02 (OR = 2.86, P = 3.03 × 10-4 ) and HLA-DRB1*16:02 (OR = 8.39, P = 1.92 × 10-3 ) were risk alleles for NMOSD susceptibility whereas HLA-DRB1*09:01 was protective (OR = 0.27, P = 1.06 × 10-5 ). Three MS risk variants were associated with susceptibility and MSGB scores were significantly higher in NMOSD than in HCs (P = 0.0095). A SNP in the KCNMA1 (potassium calcium-activated channel subfamily M alpha 1) gene was associated with disability score with genome-wide significance (rs1516512, P = 2.33 × 10-8 ) and transverse myelitis (OR = 1.77, P = 0.011). KCNMA1 was immunohistochemically detected in the perivascular endfeet of astrocytes and its immunoreactivity was markedly diminished in active spinal cord lesions in NMOSD.
INTERPRETATION: Specific HLA-DRB1 alleles confer NMOSD susceptibility and KCNMA1 is associated with disability and transverse myelitis in NMOSD.
METHODS: Genome-wide single nucleotide polymorphism (SNP) genotyping was conducted in 211 Japanese patients with NMOSD fulfilling the 2006 criteria with or without anti-aquaporin-4 (AQP4) antibody and 1,919 Japanese healthy controls (HCs). HLA-DRB1 and HLA-DPB1 alleles were genotyped in 184 NMOSD cases and 317 HCs. Multiple sclerosis (MS) risk alleles outside the major histocompatibility complex (MHC) region were tested in NMOSD and MS genetic burden (MSGB) scores were compared between HCs and NMOSD.
RESULTS: A SNP (rs1964995) in the MHC region was associated with NMOSD susceptibility (odds ratio (OR) = 2.33, P = 4.07 × 10-11 ). HLA-DRB1*08:02 (OR = 2.86, P = 3.03 × 10-4 ) and HLA-DRB1*16:02 (OR = 8.39, P = 1.92 × 10-3 ) were risk alleles for NMOSD susceptibility whereas HLA-DRB1*09:01 was protective (OR = 0.27, P = 1.06 × 10-5 ). Three MS risk variants were associated with susceptibility and MSGB scores were significantly higher in NMOSD than in HCs (P = 0.0095). A SNP in the KCNMA1 (potassium calcium-activated channel subfamily M alpha 1) gene was associated with disability score with genome-wide significance (rs1516512, P = 2.33 × 10-8 ) and transverse myelitis (OR = 1.77, P = 0.011). KCNMA1 was immunohistochemically detected in the perivascular endfeet of astrocytes and its immunoreactivity was markedly diminished in active spinal cord lesions in NMOSD.
INTERPRETATION: Specific HLA-DRB1 alleles confer NMOSD susceptibility and KCNMA1 is associated with disability and transverse myelitis in NMOSD.
Предметные рубрики MeSH
AdultAgedAged, 80 and overFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHLA-DRB1 ChainsHumansJapanLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsMaleMiddle AgedMultiple SclerosisNeuromyelitis OpticaPolymorphism, Single NucleotideProtective FactorsRisk Factors