Influence of female hormonal factors, in relation to autoantibodies and genetic markers, on the development of rheumatoid arthritis in northern Sweden: a case-control study.
OBJECTIVE
To study the influence of female hormonal factors on the development of rheumatoid arthritis (RA) in relation to the human leucocyte antigen (HLA)-DRB1 shared epitope (SE), the protein tyrosine phosphatase (PTPN22) 1858T variant, anti-citrullinated protein antibodies (ACPAs), and immunoglobulin (Ig)M-rheumatoid factor (IgM-RF).


METHODS
A case-control study (1:4) was nested within the Medical Biobank of northern Sweden. Females who had subsequently developed RA (n = 70), median of 2.7 years before the onset of symptoms, and matched controls (n = 280) were identified from among the blood donors. A questionnaire concerning previous exposures until disease onset, including hormonal and reproductive factors, and smoking habits was distributed.


RESULTS
Breastfeeding was significantly associated with the development of RA [odds ratio (OR) 4.8, 95% confidence interval (CI) 1.43-15.8]. Increasing time of breastfeeding increased the risk of RA (OR 5.7, 95% CI 1.83-17.95) for breastfeeding ≥ 17 months. In a multiple logistic regression analysis, increasing time of breastfeeding (OR 9.5, 95% CI 2.14-42.43 for ≥ 17 months), seropositivity for ACPAs (OR 19.5, 95% CI 4.47-84.81), and carriage of the PTPN22 1858T variant (OR 3.2, 95% CI 1.36-7.54) remained significant predictors of RA. Users of oral contraceptives (OC) for ≥ 7 years had a decreased risk for development of RA (OR 0.37, 95% CI 0.15-0.93).


CONCLUSIONS
A longer duration of breastfeeding increased the risk of developing RA, especially among individuals seropositive for ACPA or IgM-RF or carrying the PTPN22 1858T variant. Use of OC for ≥ 7 years was associated with a decreased risk.
Berglin
E
E
Department of Public Health and Clinical Medicine, University Hospital, Umeå, Sweden.
Kokkonen
H
H
Einarsdottir
E
E
Agren
A
A
Rantapää Dahlqvist
S
S
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D001323:Autoantibodies / Q000097:blood*; D001942:Breast Feeding / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008875:Middle Aged; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D012189:Retrospective Studies; D012217:Rheumatoid Factor / Q000276:immunology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
D001323:Autoantibodies; D003276:Contraceptives, Oral; D005819:Genetic Markers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007075:Immunoglobulin M; D012217:Rheumatoid Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22