Variation in the MC4R gene is associated with bone phenotypes in elderly Swedish women.

ABSTRACT:

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Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n?=?1061) and OPRA (age 75, n?=?1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2)?=?0.2-0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.

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100 vs. 103 vs. 103; p?=?0.002); (SOS: 1521 vs. 1526 vs. 1524; p?=?0.008); (Stiffness index: 69 vs. 73 vs. 74; p?=?0.0006) after adjustment for confounders. They also had low folate (18 vs. 17 vs. 16; p?=?0.03) and vitamin D (93 vs. 91 vs. 90; p?=?0.03) and high Hcy levels (13.7 vs 14.4 vs. 14.5; p?=?0.06). Fracture incidence was lower among women with the C-allele, (52% vs. 58%; p?=?0.067). Variation in MC4R was not associated with BMD or body composition in either OPRA or PEAK-25. SNPs close to FTO and INSIG2 were not associated with any bone phenotypes in either cohort and FTO SNPs were only associated with body composition in PEAK-25 (p?0.001). Our results suggest that genetic variation close to MC4R is associated with quantitative ultrasound and risk of fracture.

SUBMITTER: Garg G 

PROVIDER: S-EPMC3916440 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature