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The influence of human leukocyte antigen-DRB1*15: 01 and its interaction with smoking in MS development is dependent on DQA1*01
Stockholm University, Faculty of Science, Department of Mathematics.
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Number of Authors: 72019 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: HLA-DRB1*15:01, absence of HLA-A*02:01, and smoking interact to increase multiple sclerosis (MS) risk.

Objective: To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*15:01 and absence of A*02:01, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is affected by the DQA1*01:01 allele, which confers a protective effect only in the presence of DRB1*15:01.

Methods: In two Swedish population-based case-control studies (5838 cases, 5412 controls), subjects with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. Interaction on the additive scale between different genotypes and smoking was evaluated.

Results: The DRB1*08:01 allele interacted with smoking to increase MS risk. The interaction between DRB1*15:01 and both the absence of A*02:01 and smoking was confined to DQA1*01:01 negative subjects, whereas no interactions occurred among DQA1*01:01 positive subjects.

Conclusion: Multifaceted interactions take place between different class II alleles and smoking in MS development. The influence of DRB1*15:01 and its interaction with the absence of A*02:01 and smoking is dependent on DQA1*01:01 status which may be due to differences in the responding T-cell repertoires.

Place, publisher, year, edition, pages
2019.
Keywords [en]
Multiple sclerosis, HLA, smoking, gene-gene interaction, gene-environment interaction
National Category
Neurology
Identifiers
URN: urn:nbn:se:su:diva-175842DOI: 10.1177/1352458519877685ISI: 000491718700001PubMedID: 31573825OAI: oai:DiVA.org:su-175842DiVA, id: diva2:1370089
Available from: 2019-11-14 Created: 2019-11-14 Last updated: 2019-11-14

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