The association of single nucleotide polymorphisms in the calcitonin gene with primary osteoarthritis of the knee in Mexican mestizo population

Abstract

Primary osteoarthritis (OA) is a multifactorial disorder with several genetics factors involved. Calcitonin (CT) has been suggested to possess chondroprotective effects and could play an important role in the pathogenesis of OA. The aim of this study was to investigate whether genetic variations in or adjacent to the CT gene may be associated with primary OA of the knee in Mexican mestizo population. We conducted a case-control study to investigate the association between six single nucleotide polymorphisms at the CT locus and OA of the knee in 107 cases and 106 controls. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee ≥ 2. Controls were subjects >40 years of age with a radiologic score <2. Non-conditional logistic regression was developed to evaluate risk magnitude. The G allele and GT genotype frequencies of the G-706T polymorphism and the C allele and CC genotype of the C-778T polymorphism were significantly higher in patients with OA than in control subjects. The GG genotype of the G-706T was associated with lower risk of the development of OA of the knee. According to the results, the G-706T and the C-778T polymorphisms were related to the Cdx1 and Mzf1 transcription factor binding sites, respectively. Therefore, these could be related to regulation sequences in the CT gene promoter. In conclusion, G-706T and C-778T polymorphisms in the CT gene are significantly associated with the development of primary OA of the knee.

BDKRB2 +9/−9 bp polymorphisms influence BDKRB2 expression levels and NO production in knee osteoarthritis

“…3–5 In addition to the classical predisposing factors listed here, several studies have demonstrated that gene polymorphisms may be related to the pathogenesis of OA. 6–8…”

“…[3][4][5] In addition to the classical predisposing factors listed here, several studies have demonstrated that gene polymorphisms may be related to the pathogenesis of OA. [6][7][8] Currently, with limited diagnostic approaches, the major treatment of OA is to control the inflammation while managing the patient's pain. The administration of Bradykinin B2 receptor (BDKRB2) antagonists, which reportedly produce enduring analgesic effects in patients afflicted with OA of the knee, signifies the potential key role played by bradykinins in the progression of the disease.…”