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This study aimed to analyze the association between rs3480 and rs16835198 of  FNDC5/Irisin  and their haplotypes with variations in bone mineral density (BMD) and osteopenia/osteoporosis in postmenopausal Mayan-Mestizo women. We studied 547 postmenopausal women of Maya-Mestizo origin. BMD was measured in the lumbar spine and total hip by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of  FNDC5/Irisin  were studied using real-time PCR allelic discrimination. Differences between the means of BMD according to genotype were analyzed with covariance. Allele frequency differences were assessed by  χ2  and logistic regression was used to test for associations. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation  r2 , and haplotype analysis was conducted. Under a recessive model, we observed a significant association of rs3480 with the presence of osteopenia at the total hip and femoral neck ( p  = 0.008 and  p  = 0.003, respectively). For rs16835198, we found an association with osteopenia at the total hip and femoral neck in a dominant model ( p  = 0.043 and  p  = 0.009, respectively). We found an association of rs3480 with risk to present osteopenia at the total hip and femoral neck, while rs16835198 was associated as a protector for presence of osteopenia only at the femoral neck.

FNDC5/Irisin polymorphisms are associated with osteopenia in postmenopausal Mayan-Mestizo women