Association of HLA Class II alleles and haplotypes with cervical dystonia: HLA DR13-DQ6 (DQB1*0604) homozygotes are at greatly increased risk of cervical dystonia in Caucasian Americans

Abstract

An unanticipated discovery was made while examining genetics of the immune response in patients treated with botulinum neurotoxin (BoNT), which included cervical dystonia (CD) patients. Initial examination of HLA DQA1:DQB1 frequencies revealed an unexpectedly high number of DQA1*0102:DQB1*0604 homozygotes (hz) in the CD patients. We typed the BoNT-treated CD Caucasian subset for HLA-DRB1, DQA1, and DQB1 and succeeded in typing HLA-DRB1, -DQA1, and -DQB1 for 75 of the patients. Two statistical methods found the DQB1 locus associated with CD and one method found a probable association of DQB1*0604. Examination of the allele and haplotype pairing indicated that DQB1*0604 hz comprised most to all of the positive association. Other than this genotype, one other allele, DQB1*0504 contributes to the association of the DQB1 locus. These findings indicate a probable infectious and/or autoimmune component in some CD patients. However, longer distance associations within an extended and conserved DQB1*0604 bearing haplotype leave a possibility that a locus proximal to DQB1 might be involved.

Keywords::

• Cervical dystonia
• HLA association
• DRB1
• DQA1
• DQB1
• DQ6

Acknowledgments

This study was supported by an unrestricted grant from Allergan. The support of the Welch Foundation, due to the award to M.Z.A. of the Robert A. Welch Chair of Chemistry (Grant number 0007), is also gratefully acknowledged. The authors thank Mr Luis Lay, Mr Anthony Davidson, Ms Christine Hunter, Mrs Karen Flores, Mr Matt Houliston, Mr Nicholas Pokrajac, Ms Denee Dille, and Ms Masooma Naqvi for their able technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.