PMID- 31573825
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20210924
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 26
IP  - 13
DP  - 2020 Nov
TI  - The influence of human leukocyte antigen-DRB1*15:01 and its interaction with 
      smoking in MS development is dependent on DQA1*01:01 status.
PG  - 1638-1646
LID - 10.1177/1352458519877685 [doi]
AB  - 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.
FAU - Hedstrom, Anna Karin
AU  - Hedstrom AK
AD  - Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Hossjer, Ola
AU  - Hossjer O
AD  - Department of Mathematical Statistics, Stockholm University, Stockholm, Sweden.
FAU - Hillert, Jan
AU  - Hillert J
AD  - Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska 
      Institute, Karolinska University Hospital, Stockholm, Sweden.
FAU - Stridh, Pernilla
AU  - Stridh P
AD  - Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska 
      Institute, Karolinska University Hospital, Stockholm, Sweden.
FAU - Kockum, Ingrid
AU  - Kockum I
AD  - Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska 
      Institute, Karolinska University Hospital, Stockholm, Sweden.
FAU - Olsson, Tomas
AU  - Olsson T
AD  - Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska 
      Institute, Karolinska University Hospital, Stockholm, Sweden.
FAU - Alfredsson, Lars
AU  - Alfredsson L
AD  - Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191001
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Alleles
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - *HLA Antigens
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Haplotypes
MH  - Humans
MH  - *Multiple Sclerosis/genetics
MH  - Smoking/adverse effects
OTO - NOTNLM
OT  - HLA
OT  - Multiple sclerosis
OT  - gene-environment interaction
OT  - gene-gene interaction
OT  - smoking
EDAT- 2019/10/02 06:00
MHDA- 2021/09/25 06:00
CRDT- 2019/10/02 06:00
PHST- 2019/10/02 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2019/10/02 06:00 [entrez]
AID - 10.1177/1352458519877685 [doi]
PST - ppublish
SO  - Mult Scler. 2020 Nov;26(13):1638-1646. doi: 10.1177/1352458519877685. Epub 2019 
      Oct 1.