Interactions of interleukin-6 gene polymorphisms with calcium intake and physical activity on bone mass in pre-menarche Chinese girls

This study assessed independent associations and interactions of IL-6 promoter alleles (-174G/C and -634C/G), calcium intake and physical activity with bone mass among pre-menarche Chinese girls. The -634 CC carriers, greater calcium intake and physical activity were associated with better bone mass. The gene-bone association was more pronounced among girls with high physical activity or with low calcium intake. Introduction The association between interleukin (IL)-6 promoter polymorphisms and bone mass remains in debate. This cross-sectional study examined the association between the IL-6 promoter alleles (-174G/C and -634C/G) and bone mass, and assessed if the association could be modified by calcium intake or physical activity in pre-menarche Chinese girls. Methods Two-hundred and twenty-eight healthy pre-menarche girls aged 9-11 years were recruited from primary schools in Guangzhou, China by sending letters to parents. None of them had diseases or medications known to affect bone metabolism. The IL-6 promoter genotypes were determined by PCR-RFLP, and BMD and BMC at the total body, lumbar spine, total hip and femoral neck were measured by DXA. Calcium intake and physical activity were assessed by face-to-face questionnaire interview. Results One hundred and seventy-six subjects completed the entire study. We did not detect gene polymorphism at the IL-6 -174G/C locus, all were GG homozygotes. The IL-6 -634C/G polymorphism was significantly associated with both BMD and BMC even after adjusting for age and weight. Girls with CC genotype had higher levels of BMC and BMD than G allele carriers (+8.3% for the total body BMC, and +2.9%, +5.8%, and +5.7% for BMDs at the total body, total hip, and femoral neck, respectively; P < 0.05). The favorable effect of physical activity on BMDs at the total hip and femoral neck was much more pronounced in CC carriers than in G allele carriers, and the CC genotype associated higher BMDs at the total hip and femoral neck were observed only in girls with high level physical activity (P for interactions = 0.036 and 0.021, adjusted for age and weight). Calcium had a more benefit to the total body BMC in G allele carriers than in CC carriers, and the G allele-associated lower total body BMC was found only in subjects with low calcium intake. Conclusion The IL-6 -634C/G polymorphism was significantly associated with BMD and the association might be modified by calcium intake or physical activity in pre-menarche Chinese girls.