Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking
2008

Genetic Factors and Smoking Risk for Rheumatoid Arthritis

Sample size: 437 publication 10 minutes Evidence: moderate

Author Information

Author(s): Costenbader Karen H, Chang Shun-Chiao, De Vivo Immaculata, Plenge Robert, Karlson Elizabeth W

Primary Institution: Brigham and Women's Hospital, Harvard Medical School

Hypothesis

Are polymorphisms in PTPN22, PADI-4, and CTLA-4 associated with rheumatoid arthritis risk in women, particularly in relation to smoking?

Conclusion

PTPN22 is associated with increased rheumatoid arthritis risk among Caucasian women, especially in those who smoke heavily.

Supporting Evidence

  • PTPN22 was associated with increased RA risk with a pooled odds ratio of 1.46.
  • The risk was stronger for RF-positive than RF-negative RA.
  • A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed.
  • CTLA-4 and PADI-4 genotypes were not associated with RA risk in the pooled results.

Takeaway

This study found that a specific gene can increase the risk of getting rheumatoid arthritis, especially if you smoke a lot.

Methodology

The study used a nested case-control design within two cohorts of women, analyzing genetic polymorphisms and their interactions with smoking.

Potential Biases

Potential population stratification exists despite efforts to control for it.

Limitations

The study relied on self-reported data for some variables and did not follow participants longitudinally for RA disease activity.

Participant Demographics

Caucasian women aged 30 to 55 years in NHS and 25 to 42 years in NHSII.

Statistical Information

P-Value

0.04

Confidence Interval

1.02 to 2.08

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/ar2421

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