Common variants in the FTO gene are associated with body weight and obesity, which are known to be associated with osteoporosis. This study examined the association between FTO genotypes and osteoporosis phenotypes (e.g., bone mineral density (BMD), bone loss, and fracture risk) in post-menopausal women and elderly men.
The study involved 1277 women and 758 men aged 60 years and older who were part of the Dubbo Osteoporosis Epidemiology Study (since 1990). BMD at the femoral neck and lumbar spine was measured by DXA (GE-Lunar Prodigy) at baseline and every 2 years during the follow-up period (1990-2020). Fragility fractures was ascertained by X-ray report. Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using TaqMan assay. The mixed-effects model assessed the association between the SNPs and BMD or bone loss. The Cox’s proportional hazards model determined the association between SNPs and fracture risk.
The distribution of all FTO genotypes was consistent with the Hardy-Weinberg disequilibrium law. In women, carriers of the minor homozygous CC genotype (rs1421085) had a greater rate of bone loss than carriers of TC and TT genotypes (-1.14 vs -0.52 mg/cm2, P=0.001). Furthermore, carriers of the CC genotype also had a greater risk of hip fracture (hazard ratio [HR] = 1.70, 95% CI, 1.10-2.63) than those with TC and TT genotypes, and this association was independent of baseline BMD, age, and body mass index. The same associations were also observed for rs1558902, rs1121980, and rs17817449. In men, there was no statistically significant association between any SNP and bone phenotypes.
These data indicate that variants within the FTO gene is associated with bone loss and hip fracture risk in women, suggesting that the FTO gene is a potential candidate for the delineation of the relationship between obesity and osteoporosis.