PT  - JOURNAL ARTICLE
AU  - Xiaodong Zhou
AU  - Jiucun Wang
AU  - Hejian Zou
AU  - Michael M Ward
AU  - Michael H Weisman
AU  - Maribel G Espitia
AU  - Xiangjun Xiao
AU  - Effie Petersdorf
AU  - Emmanuel Mignot
AU  - Javier Martin
AU  - Lianne S Gensler
AU  - Paul Scheet
AU  - John D Reveille
TI  - MICA, a gene contributing strong susceptibility to ankylosing spondylitis
AID  - 10.1136/annrheumdis-2013-203352
DP  - 2014 Aug 01
TA  - Annals of the Rheumatic Diseases
PG  - 1552--1557
VI  - 73
IP  - 8
4099  - http://ard.bmj.com/content/73/8/1552.short
4100  - http://ard.bmj.com/content/73/8/1552.full
SO  - Ann Rheum Dis2014 Aug 01; 73
AB  - 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.