Single-Nucleotide Polymorphisms in the P2x7 Receptor Gene are Associated with Bone Mineral Density and Ankle Fractures

CATEGORY: Ankle, Basic Sciences/Biologics, Trauma, Osteoporosis INTRODUCTION/PURPOSE: The objective of this study is to determine the associations among genetic variations in the P2X7 receptor gene, decreased bone mineral density (BMD), and the risk of osteoporosis in patients older than 50 years with ankle fractures. METHODS: A Level-1 diagnostic study was conducted. Patients over 50 years of age with ankle fractures who had undergone surgical treatment were divided into two groups following the result of a bone densitometry: a study group with osteopenia (bone mineral density T score between -1 and -2.5) or osteoporosis (bone mineral density T score = -2.5) and the control group with normal values (bone mineral density T score = -1). Exclusion criteria were alterations that led to secondary osteoporosis. Patients were genotyped for 15 nonsynonymous single nucleotide polymorphisms (SNPs) within the P2X7 receptor (numbered from 1 to 15) obtained from saliva. We evaluated 121 patients with ankle fractures, 56 being from the control group, and 65 from the study group. All patients were sedentary, did not take any medication for the treatment of osteoporosis, did not smoke, and had suffered a low-impact trauma. RESULTS: The grouped assessment of the SNP alterations showed that if a gene has three or more SNP variants (36.4% of the 121 patients), out of the 15 possibilities, it is altered with clinical repercussions related to the loss or gain of the function of the gene. In evaluating the SNP alterations individually, the results suggest that: SNPs 1,4,14, and 15 are loss of function variants; SNPs 5 and 10 are described as loss of function variants; however, they have no influence on our study population; SNPs 11 and 13 are loss of function variants and not gain of function function as is described in the literature; and SNP 12 was associated with a loss of function in our population. CONCLUSION: In conclusion, we demonstrate that functional polymorphisms in P2X7 are associated with BMD and with an increased risk of ankle fractures. The limitations of our study are its focus on non-synonymous polymorphisms, which do not cover all genetic variations in P2X7, and its small sample size compared to the international literature. One of this study’s strengths is the fact it is the first to evaluate P2X7 in the Brazilian population.