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

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.

Association of the calcitonin gene (CA) polymorphism with osteoarthritis of the knee in a Mexican mestizo population.

Osteoarthritis (OA) is the most common form of destructive joint disease that is characterized by the degeneration of the articular cartilage, synovial membrane, joint capsule, and subchondral bone. The knee is a joint commonly affected for OA. Calcitonin (CT) has been suggested to have chondroprotective effects; therefore, could play a role in the pathogenesis of OA of the knee. Genetic variations in or adjacent to the CT gene may be associated with primary OA development. We conducted a case-control association study in which we examined the correlation between a dinucleotide (cytosine-adenine, CA) repeat polymorphism at the CT locus and OA of the knee in 88 patients with OA and in 111 control subjects from the Mexican mestizo population. Allele A and genotype AG frequencies were significantly higher in patients with OA than in control subjects (56.3 vs. 43.2%; p<0.001 and 40.9 vs. 26.1%; p=0.027, respectively), and were associated with the presence of OA of the knee (odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.30-5.27, and OR, 1.93; 95% CI, 1.04-3.58, respectively) using a logistic regression model adjusted for gender, age and Body mass index (BMI). The GG genotype was associated with a lower risk of OA development of the knee; thus, it may constitute a protective factor against this disease (OR, 0.40; 95% CI, 0.16-0.98). In summary, we conclude that the dinucleotide CA polymorphism in the CT gene may become a useful marker for genetic studies of OA of the knee in Mexican population.