Association Between Osteoprotegerin G1181C and T245G Polymorphisms And Charcot Diabetic Neuroarthropathy: a case – control study

doi:10.2337/dc09-0243

Association Between Osteoprotegerin G1181C and T245G Polymorphisms And Charcot Diabetic Neuroarthropathy: a case – control study

Dario Pitocco, MD (dario.pitocco{at}rm.unicatt.it)¹,
Giovanni Zelano, MD²,³,
Giuseppina Gioffrè, MD⁴,
Enrico Di Stasio, MD⁵,
Francesco Zaccardi, MD⁶,
Francesca Martini, MD⁶,
Tittania Musella, MD⁶,
Giuseppe Scavone, MD⁶,
Marco Galli, MD⁷,
Salvatore Caputo, MD¹,
Lorena Mancini, MD⁴ and
Giovanni Ghirlanda, MD¹

1 Institute of Internal Medicine, Policlinico “A. Gemelli”, Rome, Italy
2 Institute of Human Anatomy and Cell Biology, Policlinico “A. Gemelli”, Rome, Italy
3 Rehabilitation Research Center “Armonia”, Latina, Italy
4 Foot Care Unit, Policlinico “A. Gemelli”, Rome, Italy
5 Institute of Biochemistry, Policlinico “A. Gemelli”, Rome, Italy
6 Diabetes Center, Policlinico “A. Gemelli”, Rome, Italy
7 Institute of Orthopedic Surgery, Policlinico “A. Gemelli”, Rome, Italy

Abstract

Objective: Charcot neuroarthropathy (CN) is a disabling complication of diabetes mellitus. Although its pathogenesis remains unknown, we suppose that genetics might play a relevant role.

Research Design and Methods: We performed a case-control study with 59 subjects with diabetic CN (Ch), 41 with diabetic neuropathy without Charcot (ND) and 103 healthy controls (H), to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of CN.

Results: Regarding the SNPs of G1181C, was found a significant linkage between G allele and Charcot (Ch vs ND, OR=2.32 [CI 1.3-4.1, p=0.006]; Ch vs H, OR=2.10 [CI 1.3-3.3, p=0.002]; ND vs H, OR=0.90 [CI 0.7-1.9, p=0.452]); similarly, we found a linkage with G allele of T245G (Ch vs ND, OR=6.25 [CI 2.2-19.7, p<0.001]; Ch vs H, OR=3.56 [CI 1.9-6.7, p=0.001]; ND vs H, OR=0.54 [CI 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 subjects compared to H (OR=0.18 [CI 0.06-0.5 p=0.002]) and to ND (OR=0.17 [CI 0.05-0.58, p=0.006]), while there was not difference between H and ND (OR=1.05 [CI 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 CN.

Conclusions: This is the first study that shows an association between genetic regulation of bone remodelling and CN.