Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of cigarette smoking and systemic lupus erythematosus in a Japanese population.
OBJECTIVE
Exposure to reactive oxygen species (ROS) through cigarette smoking is thought to contribute to the development of systemic lupus erythematosus (SLE). Metabolic enzymes are involved in ROS production. The aim of this study was to evaluate the modifying effect of metabolic polymorphisms on the association of cigarette smoking with SLE risk in a Japanese population.


METHODS
We investigated the relationship of the cytochrome P450 (CYP) 1A1 rs4646903 and glutathione S-transferase (GST) M1 deletion polymorphisms to SLE risk with attention to interaction with cigarette smoking among 151 SLE cases and 421 controls in female Japanese subjects. Unconditional logistic regression was used to compute the odds ratios (ORs) and their 95% confidence intervals (CIs), with adjustments for several covariates.


RESULTS
Smokers with the CC genotype of CYP1A1 rs4646903 were significantly associated with increased risk of SLE (OR 9.72, 95% CI 2.73-34.6). Similarly, smokers with the combined CYP1A1 rs4646903/GSTM1 'at-risk' genotype were significantly associated with increased risk of SLE (OR 17.5, 95% CI 3.20-95.9). More than 60% of the excess risk for SLE in smokers with the CC genotype and smokers with the combined 'at-risk' genotype was due to an additive interaction. A lack of association of the GSTM1 genotypes with smoking was observed.


CONCLUSIONS
Our results suggest that a combination of smoking and either the CYP1A1 rs4646903 genotype or the combined metabolic genotype plays an important role in SLE susceptibility in our Japanese population. Additional studies are warranted to confirm the metabolic polymorphism-smoking interaction suggested in the present study.
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. chikako@phealth.med.kyushu-u.ac.jp
C
C
Kiyohara
M
M
Washio
T
T
Horiuchi
T
T
Asami
S
S
Ide
T
T
Atsumi
G
G
Kobashi
H
H
Takahashi
Y
Y
Tada
D000328:Adult; D015897:Comorbidity; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014029:Tobacco Use Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C569463:CYP1A1 protein, human