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A Prospective Study Investigating Prediagnostic Leukocyte Telomere Length and Risk of Developing Rheumatoid Arthritis
Jennifer Prescott1, Elizabeth W Karlson2, Esther H Orr2
1From the Channing Division of Network Medicine, and the Division of Rheumatology, Allergy, and Immunology, and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard TH Chan School of Public Health; Department of Pediatric Dentistry, Tufts University School of Dental Medicine, Boston, Massachusetts, USA.J. Prescott, PhD, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard TH Chan School of Public Health; E.H. Orr, BS, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard TH Chan School of Public Health; I. De Vivo, PhD, MPH, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard TH Chan School of Public Health; E.W. Karlson, MD, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; K.H. Costenbader, MD, MPH, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; R.Y. Zee, BDS, PhD, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and Department of Pediatric Dentistry, Tufts University School of Dental Medicine. nhjxp@channing.harvard.edu.
Objective:
To prospectively examine the association between leukocyte telomere length (LTL) and subsequent rheumatoid arthritis (RA) development in women.
Methods:
Using a case-control design nested within the prospective Nurses' Health Study (NHS), NHS II (NHSII), and Women's Health Study (WHS), each validated case of RA with a prediagnostic blood sample was matched to 3 controls by cohort, age, menopausal status, postmenopausal hormone therapy, and blood collection covariates. We measured telomere length in genomic DNA extracted from stored buffy coat samples using quantitative PCR. We used unconditional logistic regression to determine OR and 95% CI, and random-effects metaanalysis to combine study results.
Results:
In total, we analyzed 296 incident RA cases and 827 matched controls. Mean age of diagnosis among women who developed RA was 60.5 in NHS/NHSII and 61.3 in WHS. Metaanalysis demonstrated that longer prediagnostic LTL was associated with increased RA risk when women in the longest versus shortest LTL tertile were compared (OR 1.51, 95% CI 1.03-2.23, Pheterogeneity = 0.27). However, statistically significant between-study heterogeneity was observed for the intermediate tertile category (Pheterogeneity = 0.008). We did not observe heterogeneity by menopausal status, inflammatory cytokine levels, age at diagnosis, age at blood collection, body mass index, seropositivity, or HLA-DRβ1 shared epitope status.
Conclusion:
Our results do not support an involvement for short LTL preceding RA development.
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