Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population.
OBJECTIVE
Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. Similarly, tumor necrosis factor receptor superfamily, member 1B (TNFRSF1B) has been reported to be associated with SLE risk in Japanese populations. Along with environmental factors such as smoking, both polymorphisms may modulate an individual's susceptibility to SLE. We investigated these relationships in a case-control study to evaluate risk factors for SLE among Japanese women.


METHODS
We investigated the relationship of the STAT4 rs7574865 and TNFRSF1B rs1061622 polymorphisms to SLE risk with special reference to their combination and interaction with cigarette smoking among 152 SLE cases and 427 controls.


RESULTS
The TT genotype of STAT4 rs7574865 was significantly associated with increased risk of SLE (OR 2.21, 95% CI 1.10-4.68). Subjects with at least one G allele of TNFRSF1B rs1061622 had an increased risk of SLE (OR 1.56, 95% CI 0.99-2.47). The attributable proportion due to the interaction between the TNFRSF1B rs1061622 genotypes and smoking was estimated to be 0.49 (95% CI 0.07-0.92), indicating that 49% of the excess risk for SLE in smokers with at least one G allele was due to an additive interaction. A lack of significant associations of STAT4 with smoking was observed. No significant gene-gene interactions were found among polymorphisms of STAT4 and TNFRSF1B.


CONCLUSIONS
Our findings suggest that the association between cigarette smoking and SLE could be differentiated by the TNFRSF1B rs1061622 T allele among female Japanese subjects. This preliminary exploratory result should be confirmed in a larger study.
Kiyohara
Chikako
C
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. chikako@phealth.med.kyushu-u.ac.jp
Washio
Masakazu
M
Horiuchi
Takahiko
T
Tada
Yoshifumi
Y
Asami
Toyoko
T
Ide
Saburo
S
Atsumi
Tatsuya
T
Kobashi
Gen
G
Takahashi
Hiroki
H
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
D047889:Receptors, Tumor Necrosis Factor, Type II; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C415902:TNFRSF1B protein, human