Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis–associated haplotypes at 11 loci. Two ankylosing spondylitis–associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.
Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.
The goal of this paper is to examine the trapezius muscle tone by measuring simultaneously using Myoton-2 myometer i.e., the natural oscillation frequency, stiffness and the elasticity of the trapezius muscle. With this method, the mechanical response of the muscle, to a short applied mechanical impulse, is registered by an acceleration probe. From the acquired damped natural oscillation waveform, the frequency (Hz), the stiffness (N/m) and the logarithmic decrement of damping (characterizing tissue's elasticity) are calculated, quantifying the functional state of the muscle. The trapezius muscle on both sides of the body was tested in twenty adult women by two investigators using the Myoton-2 myometer. During the measurements, the subjects were in a relaxed sitting position. The Bland and Altman graphical test, comparing the differences of the measurements of two investigators, was used for assessing the inter-observer repeatability. The registered values for the trapezius muscle tension, stiffness and elasticity are varying between the tested subjects, but the intra-class correlation coefficient (ICC) was near 1 for three muscular properties, showing that the variation within the subject (due to the investigator) is negligible, compared with the variation between the subjects.
This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.
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