Association Between Osteoprotegerin G1181C and T245G Polymorphisms and Diabetic Charcot Neuroarthropathy
A case-control study
- Dario Pitocco, MD1,
- Giovanni Zelano, MD2,
- Giuseppina Gioffrè, MD3,
- Enrico Di Stasio, MD4,
- Francesco Zaccardi, MD5,
- Francesca Martini, MD5,
- Tittania Musella, MD5,
- Giuseppe Scavone, MD5,
- Marco Galli, MD6,
- Salvatore Caputo, MD1,
- Lorena Mancini, MD3 and
- Giovanni Ghirlanda, MD1
- 1Institute of Internal Medicine, Policlinico “A. Gemelli,” Rome, Italy;
- 2Institute of Human Anatomy and Cell Biology, Policlinico “A. Gemelli,” Rome, Italy, and the Rehabilitation Research Center “Armonia,” Latina, Italy;
- 3Foot Care Unit, Policlinico “A. Gemelli,” Rome, Italy;
- 4Institute of Biochemistry, Policlinico “A. Gemelli,” Rome, Italy;
- 5Diabetes Center, Policlinico “A. Gemelli,” Rome, Italy;
- 6Institute of Orthopedic Surgery, Policlinico “A. Gemelli,” Rome, Italy.
- Corresponding author: Dario Pitocco, dario.pitocco{at}rm.unicatt.it.
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D.P. and G.Z. contributed equally to this study.
Abstract
OBJECTIVE Charcot neuroarthropathy is a disabling complication of diabetes. Although its pathogenesis remains unknown, we suppose that genetics may play a relevant role.
RESEARCH DESIGN AND METHODS We performed a case-control study with 59 subjects with diabetic Charcot neuroarthropathy (Ch group), 41 with diabetic neuropathy without Charcot neuroarthropathy (ND group), and 103 healthy control subjects (H group) to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of Charcot neuroarthropathy.
RESULTS Regarding the SNPs of G1181C, we found a significant linkage between the G allele and Charcot neuroarthropathy (Ch vs. ND, odds ratio [OR] 2.32 [95% CI 1.3–4.1], P = 0.006; Ch vs. H, 2.10 [1.3–3.3], P = 0.002; and ND vs. H, 0.90 [0.7–1.9], P = 0.452); similarly, we found a linkage with the G allele of T245G (Ch vs. ND, 6.25 [2.2–19.7], P < 0.001; Ch vs. H, 3.56 [1.9–6.7], P = 0.001; and ND vs. H, 0.54 [0.6–5.7], P = 0.304), supporting a protective role for the allele C and T, respectively. For this reason we investigated the frequency of the protective double homozygosis CC + TT (7% in Ch) that was significantly lower in Ch compared with H (0.18 [0.06–0.5], P = 0.002) and with ND (0.17 [0.05–0.58], P = 0.006), whereas there was no difference between H and ND (1.05 [0.43–2.0], P = 0.468). In a multivariate logistic backward regression model, only weight and the lack of CC and TT genotypes were independently associated with the presence of Charcot neuroarthropathy.
CONCLUSIONS This is the first study that shows an association between genetic regulation of bone remodeling and Charcot neuroarthropathy.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received February 11, 2009.
- Accepted June 1, 2009.
- © 2009 by the American Diabetes Association.
