AUTHOR=Li Huan , Xiao Lulu , Wang Liang , Lin Jinfu , Luo Min , Chen Menglong , He Ruojie , Zhu Yuling , Zhang Cheng 

TITLE=HLA Polymorphism Affects Risk of de novo Mutation of dystrophin Gene and Clinical Severity of Duchenne Muscular Dystrophy in a Southern Chinese Population

JOURNAL=Frontiers in Neurology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00970

DOI=10.3389/fneur.2018.00970

ISSN=1664-2295

ABSTRACT=<p>Immune-mediated pathology has been thought to be an important factor contributing to Duchenne muscular dystrophy (DMD). Allele frequencies of certain HLA types are known to differ between patients with dystrophinopathies and healthy controls with low-resolution HLA gene typing data in limit reports. Using Polymerase chain reactionsequence based typing (PCR-SBT) to genotype 64 children with DMD in <italic>HLA-A</italic>, -B,-C, -DRB1, and <italic>-DQB1</italic> locus and 503 healthy controls in <italic>HLA-A</italic>, -<italic>B, -DRB1</italic> locus, this study aimed to investigate associations of specific <italic>HLA</italic> alleles with, and their possible roles in the development and clinical phenotypic severity of DMD. The χ<sup>2</sup> test was used to evaluate the distribution of allele frequencies in <italic>HLA-A</italic>, -<italic>B, -DRB1</italic> locus between the patients and healthy controls. A significantly higher frequency of <italic>HLA-B</italic><sup>*</sup><italic>07:05</italic> was found in children with DMD compared to that in controls (OR = 16.2, 95%CI = 2.9–89.3, <italic>P</italic> &lt; 0.046). More importantly, significantly higher frequencies of <italic>HLA-A</italic><sup>*</sup><italic>29:01</italic> (OR = 77.308, 95%CI = 6.794–879.731, <italic>P</italic> &lt; 0.0160) and <italic>HLA-B</italic><sup>*</sup>07:05 (OR = 60.240, 95%CI = 9.637–376.535, <italic>P</italic> &lt; 2.41<sup>*</sup>10<sup>−3</sup>) was found in patients with <italic>de novo</italic> mutations (<italic>n</italic> = 14) compared to controls while no difference of HLA alleles frequency ware indicated between patients with inherited mutation and control. The result indicates that <italic>HLA</italic> alleles is associated with pathogenesis of DMD especially DMD with <italic>de novo</italic> mutation. We use Vignos scale to estimate the lower limb motor function of patients. The impact of HLA alleles on score of Vignos scale of DMD children was estimated by multiple linear regression. Our study indicates that <italic>HLA-A</italic><sup>*</sup>02:01 may have a dampening effect on the clinical phenotypic severity of DMD, evidenced by the presence of <italic>HLA-A</italic><sup>*</sup>02:01 being associated with lower Vignos score. Our study demonstrates that certain <italic>HLA</italic> alleles are indeed associated with the pathogenesis and clinical phenotypic severity of DMD.</p>