The influence of human leukocyte antigen-DRB115:01 and its interaction with smoking in MS development is dependent on DQA101:01 status

• Published in: Multiple sclerosis Vol. 26; no. 13; p. 1638
• Main Authors: Hedström, Anna Karin, Hössjer, Ola, Hillert, Jan, Stridh, Pernilla, Kockum, Ingrid, Olsson, Tomas, Alfredsson, Lars
• Format: Journal Article
• Language: English
• Published: England 01.11.2020
• Subjects: gene–environment interaction; Multiple sclerosis; HLA; gene–gene interaction; smoking
• ISSN: 1477-0970
• DOI: 10.1177/1352458519877685

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