TUMOR NECROSIS FACTOR- α, INTERLEUKIN-6 AND INTERLEUKIN-10 POLYMORPHISMS IN WOMEN WITH OSTEOPOROSIS

Context: Genetic linkage and association studies have reported inconsistent findings regarding the roles of TNF-α, IL-6 and IL-10 in mass regulation, with SNP– osteoporosis associations varying across ethnic populations. Objective: To investigate the distribution of cytokine genotypes and allele frequencies in women with osteoporosis. Design: Case-control study. Setting: University outpatient clinic. Patients: Ninety-six women with osteoporosis and 48 healthy women serving as controls. Main Outcome Measures: Associations between cytokine gene polymorphisms, osteoporosis, and osteoporotic fractures were planned a priori. Results: A allele of the TNF-α rs1800629 was significantly less frequent in the osteoporotic group than in controls (OR = 0.40, 95% CI: 0.19–0.86, p = 0.019, A vs G). The GG genotype was more prevalent in osteoporotic group (86%) compared with GA (12.9%) or AA genotypes (1.1%). The IL-10 rs1800896 AA genotype was not associated with vertebral fractures, whereas carriers of the GG or GA genotypes had higher number of vertebral fractures (p < 0.0005). A gene-gene interaction between TNF-a rs1800629 GA/AA and IL-10 rs1800896 GG/GA was protective against osteoporosis (OR = 0.31, 95% CI: 0.10–0.98, p = 0.046). Conversely, the interaction between TNF-α rs1800629 GG and IL-6 rs1800795 GG/GC increased the risk of osteoporosis (OR: 2.49, 95% CI: 1.01-6.15; p= 0.048) and fractures (OR: 5.41, 95% CI: 1.18–24.72; p = 0.029). Combining IL-6 rs1800795 GG/GC with TNF-α rs1800629 GA/AA significantly decreased osteoporosis risk (OR = 0.29, 95% CI: 0.09–0.92; p = 0.037). Conclusion: TNF-α rs1800629 variant appears to confer protection against osteoporosis and fractures regardless of menopausal status.