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MICA, a gene contributing strong susceptibility to ankylosing spondylitis

Objective The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide assoc... Full description

Journal Title: Annals of the Rheumatic Diseases 2014-08, Vol.73 (8), p.1552-1557
Main Author: Zhou, Xiaodong
Other Authors: Wang, Jiucun , Zou, Hejian , Ward, Michael M , Weisman, Michael H , Espitia, Maribel G , Xiao, Xiangjun , Petersdorf, Effie , Mignot, Emmanuel , Martin, Javier , Gensler, Lianne S , Scheet, Paul , Reveille, John D
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
Publisher: England: BMJ Publishing Group Ltd
ID: ISSN: 0003-4967
Link: https://www.ncbi.nlm.nih.gov/pubmed/23727634
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recordid: cdi_proquest_journals_1777903299
title: MICA, a gene contributing strong susceptibility to ankylosing spondylitis
format: Article
creator:
  • Zhou, Xiaodong
  • Wang, Jiucun
  • Zou, Hejian
  • Ward, Michael M
  • Weisman, Michael H
  • Espitia, Maribel G
  • Xiao, Xiangjun
  • Petersdorf, Effie
  • Mignot, Emmanuel
  • Martin, Javier
  • Gensler, Lianne S
  • Scheet, Paul
  • Reveille, John D
subjects:
  • Adult
  • Analysis
  • Ankylosing spondylitis
  • Article
  • Asian Americans - genetics
  • Asian Americans - statistics & numerical data
  • Care and treatment
  • Chronic illnesses
  • Cohort Studies
  • Deoxyribonucleic acid
  • Disease
  • DNA
  • European Continental Ancestry Group - genetics
  • European Continental Ancestry Group - statistics & numerical data
  • Female
  • Genealogy
  • Genes
  • Genetic Markers
  • Genetic Predisposition to Disease - ethnology
  • Genetic Predisposition to Disease - genetics
  • Genomes
  • Histocompatibility Antigens Class I - genetics
  • HLA-B Antigens - genetics
  • Humans
  • Immune response
  • Inflammation
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Pathogenesis
  • Risk Factors
  • Spondylitis, Ankylosing - ethnology
  • Spondylitis, Ankylosing - genetics
  • Studies
  • United States - epidemiology
  • White people
  • Womens health
ispartof: Annals of the Rheumatic Diseases, 2014-08, Vol.73 (8), p.1552-1557
description: Objective The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS. Methods We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term. Results Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS. Conclusions Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.
language: eng
source:
identifier: ISSN: 0003-4967
fulltext: no_fulltext
issn:
  • 0003-4967
  • 1468-2060
url: Link


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titleMICA, a gene contributing strong susceptibility to ankylosing spondylitis
creatorZhou, Xiaodong ; Wang, Jiucun ; Zou, Hejian ; Ward, Michael M ; Weisman, Michael H ; Espitia, Maribel G ; Xiao, Xiangjun ; Petersdorf, Effie ; Mignot, Emmanuel ; Martin, Javier ; Gensler, Lianne S ; Scheet, Paul ; Reveille, John D
creatorcontribZhou, Xiaodong ; Wang, Jiucun ; Zou, Hejian ; Ward, Michael M ; Weisman, Michael H ; Espitia, Maribel G ; Xiao, Xiangjun ; Petersdorf, Effie ; Mignot, Emmanuel ; Martin, Javier ; Gensler, Lianne S ; Scheet, Paul ; Reveille, John D
descriptionObjective The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS. Methods We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term. Results Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS. Conclusions Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.
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subjectAdult ; Analysis ; Ankylosing spondylitis ; Article ; Asian Americans - genetics ; Asian Americans - statistics & numerical data ; Care and treatment ; Chronic illnesses ; Cohort Studies ; Deoxyribonucleic acid ; Disease ; DNA ; European Continental Ancestry Group - genetics ; European Continental Ancestry Group - statistics & numerical data ; Female ; Genealogy ; Genes ; Genetic Markers ; Genetic Predisposition to Disease - ethnology ; Genetic Predisposition to Disease - genetics ; Genomes ; Histocompatibility Antigens Class I - genetics ; HLA-B Antigens - genetics ; Humans ; Immune response ; Inflammation ; Linkage Disequilibrium ; Male ; Middle Aged ; Pathogenesis ; Risk Factors ; Spondylitis, Ankylosing - ethnology ; Spondylitis, Ankylosing - genetics ; Studies ; United States - epidemiology ; White people ; Womens health
ispartofAnnals of the Rheumatic Diseases, 2014-08, Vol.73 (8), p.1552-1557
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descriptionObjective The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS. Methods We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term. Results Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS. Conclusions Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.
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13European Continental Ancestry Group - statistics & numerical data
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15Genealogy
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18Genetic Predisposition to Disease - ethnology
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abstractObjective The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS. Methods We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term. Results Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS. Conclusions Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.
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