HLA-DQA1*04:01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences

ABSTRACT Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

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Post‐mortem multiple sclerosis lesion pathology is influenced by single nucleotide polymorphisms

Brain Pathology ◽

10.1111/bpa.12760 ◽

2019 ◽

Vol 30 (1) ◽

pp. 106-119 ◽

Cited By ~ 4

Author(s):

Nina L. Fransen ◽

Jakob B. A. Crusius ◽

Joost Smolders ◽

Mark R. Mizee ◽

Corbert G. Eden ◽

...

Keyword(s):

Multiple Sclerosis ◽

Single Nucleotide Polymorphisms ◽

Multiple Sclerosis Lesion ◽

Post Mortem ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Multiplex, fluorescent, solid-phase minisequencing for efficient screening of DNA sequence variation

Clinical Chemistry ◽

10.1093/clinchem/42.9.1391 ◽

1996 ◽

Vol 42 (9) ◽

pp. 1391-1397 ◽

Cited By ~ 59

Author(s):

T Pastinen ◽

J Partanen ◽

A C Syvänen

Keyword(s):

Single Nucleotide Polymorphisms ◽

Solid Phase ◽

Point Mutations ◽

Nucleotide Polymorphisms ◽

Dna Templates ◽

Single Nucleotide ◽

Large Numbers ◽

Dna Sequence Variation ◽

Hla Dqa1 ◽

Efficient Screening

Abstract We developed a multiplex, solid-phase minisequencing method to detect multiple single-nucleotide polymorphisms in an undivided sample. The amplified DNA templates are first captured on a manifold. Then, with multiple minisequencing primers of various sizes, single-nucleotide extension reactions are carried out simultaneously with fluorescently labeled dideoxynucleotides. The size of the extended product, determined by using a DNA sequencing instrument, defines the site of the polymorphisms, and the incorporated nucleotide gives the identity of the nucleotide at each site. HLA-DQA1 typing was used as a model system to evaluate the method. The DR2 subgroup of the HLA-DRB1 gene was typed along with the DQA1 gene to demonstrate the feasibility of the method in analyzing multiple genes at multiple sites simultaneously. The method is generally applicable for screening any single-nucleotide polymorphisms or point mutations, and its manifold format allows practical handling of large numbers of samples.

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