Background: The interleukin-6 gene (IL-6) stimulates osteoclast development; therefore, it has been implicated in osteoporosis. In this study, the association of osteoporosis with three IL-6 gene markers (a CA dinucleotide repeat and two single nucleotide polymorphisms [SNPs]: G-174C and G-572C) was tested in the Mexican population.
Methods: Population sample was comprised of 70 osteoporotic women, 70 non-osteoporotic women, and 500 subjects from the general population who were genotyped for the IL-6 markers. SNPs were analyzed by real-time PCR using the 5' exonuclease assay, whereas the CA dinucleotide polymorphism was evaluated by PCR and capillary electrophoresis. The allele-phenotype relationship was analyzed with the statistical method STRAT that considered population stratification and the results were adjusted with potential confounders for osteoporosis by a longitudinal multivariate model.
Results: We found that the C allele of the G-174C SNP and the A3 allele of the CA polymorphism are associated with increased bone mineral density (BMD) (p<0.0001), whereas the G-572C SNP is not (p=0.19). In concordance, subjects heterozygous for the A3 allele have higher BMD and T score average values (90.75% and -0.87, respectively) than those who did not present any A3 allele (81.4% and -1.45, respectively). Likewise, subjects with the CC genotype of the G-174 SNP have higher BMD (96.5%) and T score average value (-0.33) than those bearing the CG or GG genotype (lumbar BMD, 88.5 and 79.98%, respectively; T score: -1.07 and -1.75, respectively).
Conclusions: The CA repeat and the G-174C SNP of the IL-6 gene may become useful markers for osteoporosis in the Mexican population.