The influence of human leukocyte antigen-DRB1*15:01 and its interaction with smoking in MS development is dependent on DQA1*01:01 status.

ABSTRACT

BACKGROUND: HLA-DRB1*1501, absence of HLA-A*0201, and smoking interact to increase multiple sclerosis (MS) risk. OBJECTIVE: To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*1501 and absence of A*0201, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is affected by the DQA1*0101 allele, which confers a protective effect only in the presence of DRB1*1501. 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*0801 allele interacted with smoking to increase MS risk. The interaction between DRB1*1501 and both the absence of A*0201 and smoking was confined to DQA1*0101 negative subjects, whereas no interactions occurred among DQA1*0101 positive subjects. CONCLUSION: Multifaceted interactions take place between different class II alleles and smoking in MS development. The influence of DRB1*1501 and its interaction with the absence of A*0201 and smoking is dependent on DQA1*0101 status which may be due to differences in the responding T-cell repertoires.