Smoking, genetic risk factor, and RA
Smoking, genetic risk factor, and RA
Oct 13, 2004
Stockholm, Sweden - Smoking is an important environmental trigger for seropositive rheumatoid arthritis (RA) in people who have at least 1 copy of the HLA-DR shared epitope (SE) gene, Dr Leonid Padyukov (Karolinska Institute, Stockholm, Sweden) reports in the October 2004 issue of Arthritis & Rheumatism [ 1].
We found a notable increase in the relative risk of seropositive RA in individuals who both smoke and have the SE gene, and it is greater in individuals with 2 copies of SE.
"We found a notable increase in the relative risk of seropositive RA in individuals who both smoke and have the SE gene, and it is greater in individuals with 2 copies of SE," Padyukov tells rheumawire.
Study finds strong gene-environment interaction in RA
The shared epitope of HLA-DR is the main genetic risk factor for RA. Smoking is an important environmental risk factor. Padyukov and colleagues in the Epidemiological Investigation of Rheumatoid Arthritis Study Group conducted a population-based case-control study to examine the interaction between these 2 risk factors.
The study included 858 newly diagnosed cases of RA and 1048 matched control subjects from the general population. Both groups were classified according to smoking status and HLA-DRB1 genotypes. The study included only current smokers and never smokers; former smokers were excluded. These investigators had previously demonstrated a relationship between the risk of RA and the cumulative dose of smoking. This risk decreased with time after smoking cessation [ 2].
This analysis showed that smokers bearing 2 copies of the SE allele are nearly 16 times more likely to develop rheumatoid factor (RF)-seropositive RA than are never smokers without SE genes. Smokers with only 1 copy of the SE allele have a relative risk of 7.5 compared with never smokers without SE. Never smokers with SE have a relative risk of RF+ RA of 2.8, while smokers without SE have a relative risk of 2.4.
"The data demonstrate that the risk associated with 1 of the classic genetically defined risk factors for an autoimmune disease is strongly influenced by the presence of an environmental factor—smoking," the investigators write.
Effect seen in seropositive but not seronegative RA
Neither smoking nor the SE gene increased the risk of RF-seronegative RA. "We do not have good explanation yet for this difference," Padyukov says. "One way to answer this question is to say that the mechanisms behind seropositive and seronegative arthritis could be different, although they cause similar symptoms of rheumatoid arthritis."
Padyukov says that this study opens new perspectives for the study of RA. "From the experimental point of view, we have to study in animal models mechanisms related to the initiation of inflammation and arthritis-related symptoms by smoke and tobacco substances. From the epidemiological point of view, we should suggest revising data on different risk factors for RA by taking patients with seropositive and seronegative arthritis as separate groups, as well as by considering smoking as very important parameter in genetic studies of RA. From the clinical point of view, we suggest studying the effects in seropositive patients of quitting smoking. From the pharmacological point of view, we could suggest that smoking and SE genes should be considered as important factors affecting disease activity in the course of drug trials."
Stockholm, Sweden - Smoking is an important environmental trigger for seropositive rheumatoid arthritis (RA) in people who have at least 1 copy of the HLA-DR shared epitope (SE) gene, Dr Leonid Padyukov (Karolinska Institute, Stockholm, Sweden) reports in the October 2004 issue of Arthritis & Rheumatism [ 1].
We found a notable increase in the relative risk of seropositive RA in individuals who both smoke and have the SE gene, and it is greater in individuals with 2 copies of SE.
"We found a notable increase in the relative risk of seropositive RA in individuals who both smoke and have the SE gene, and it is greater in individuals with 2 copies of SE," Padyukov tells rheumawire.
Study finds strong gene-environment interaction in RA
The shared epitope of HLA-DR is the main genetic risk factor for RA. Smoking is an important environmental risk factor. Padyukov and colleagues in the Epidemiological Investigation of Rheumatoid Arthritis Study Group conducted a population-based case-control study to examine the interaction between these 2 risk factors.
The study included 858 newly diagnosed cases of RA and 1048 matched control subjects from the general population. Both groups were classified according to smoking status and HLA-DRB1 genotypes. The study included only current smokers and never smokers; former smokers were excluded. These investigators had previously demonstrated a relationship between the risk of RA and the cumulative dose of smoking. This risk decreased with time after smoking cessation [ 2].
This analysis showed that smokers bearing 2 copies of the SE allele are nearly 16 times more likely to develop rheumatoid factor (RF)-seropositive RA than are never smokers without SE genes. Smokers with only 1 copy of the SE allele have a relative risk of 7.5 compared with never smokers without SE. Never smokers with SE have a relative risk of RF+ RA of 2.8, while smokers without SE have a relative risk of 2.4.
"The data demonstrate that the risk associated with 1 of the classic genetically defined risk factors for an autoimmune disease is strongly influenced by the presence of an environmental factor—smoking," the investigators write.
Effect seen in seropositive but not seronegative RA
Neither smoking nor the SE gene increased the risk of RF-seronegative RA. "We do not have good explanation yet for this difference," Padyukov says. "One way to answer this question is to say that the mechanisms behind seropositive and seronegative arthritis could be different, although they cause similar symptoms of rheumatoid arthritis."
Padyukov says that this study opens new perspectives for the study of RA. "From the experimental point of view, we have to study in animal models mechanisms related to the initiation of inflammation and arthritis-related symptoms by smoke and tobacco substances. From the epidemiological point of view, we should suggest revising data on different risk factors for RA by taking patients with seropositive and seronegative arthritis as separate groups, as well as by considering smoking as very important parameter in genetic studies of RA. From the clinical point of view, we suggest studying the effects in seropositive patients of quitting smoking. From the pharmacological point of view, we could suggest that smoking and SE genes should be considered as important factors affecting disease activity in the course of drug trials."
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