Genomic Variants of Alpha-Tocopherol Associated with Bone Mineral Density

by | Aug 30, 2021 | 2021, Antioxidants, Bone Health

Written by Chrystal Moulton, Staff Writer. Two single nucleotide polymorphisms (SNPs) linked to circulating alpha-tocopherol are strongly associated with estimated bone mineral density (P < 0.001). 

x-ray of woman's hipThe risk of bone loss and fracture is dependent on environmental factors, genotype, and lifestyle factors 1. As we advance in age the risk of bone loss increases and studies have shown that oxidative stress plays a definite role in skeletal aging, loss of bone mineral density, and cellular aging, thus contributing to the risk of bone fracture 2. Antioxidants, particularly alpha-tocopherol, has been shown to lower oxidative stress and favorably affect bone mineral density (BMD) 3,4. Genes that specifically affect biomarkers can be used to study the association of (or possible causal relationship between) a particular biomarker and a disease. This approach is referred to as mendelian randomization 2,5. To date, this approach has not been used to study the relationship between alpha-tocopherol and bone mineral density. In the current trial, researchers analyzed existing data to evaluate the relationship between genetically predicted circulating alpha-tocopherol and bone mineral density (BMD) 5.

In a mendelian randomization study, researchers evaluated the association between genetic variants related to circulating alpha-tocopherol with estimated BMD. Researchers identified three single nucleotide polymorphisms (SNPs) associated with circulating alpha-tocopherol concentrations in a previous meta-analysis over 7781 persons of European ancestry 6. These three single nucleotide polymorphisms (SNPs) are: Rs 964184 close to BUD13 gene, Rs 210-8622 close to CYP4F2 gene, and Rs 11057830 close to SCARB1 gene. Data from genome wide association studies were used to assess the association between alpha-tocopherol related SNPs and estimated BMD. Genome wide association studies using heel quantitative ultrasound contain data from 426,824 participants and fracture data containing 426,795 participants (53,184 cases and 373,611 non-cases) 7.  Fractures of the hands and feet, face and skull, pathological fractures caused by malignancy, periprosthetic fractures, atypical femoral fractures, and restored fractures were not included in this analysis. Structures were identified using ICD-10 codes identified by hospital episode statistics (n= 20,122) and self-reported data (n = 48,818). Average estimated BMD levels in men was 0.56 ±0.12 g/cm2 and for women 0.51 ±0.11 g/cm2 6. Researchers also searched a database called the PhenoScanner to find out whether the alpha-tocopherol associated SNPs were associated with risk factors for low BMD or fractures. Mendelian randomization estimates were made per one standard deviation increment of the association between serum alpha-tocopherol with BMD and fracture risk.

Of the three alpha-tocopherol associated SNPs, the Rs 11057830 (near SCAR B1 gene) and Rs 2108622 (near CYP4F2 gene) are strongly associated with estimated BMD (P < 0.001). The genetic assessment showed that one standard deviation increment in circulating alpha-tocopherol levels is associated with 0.07 g/cm2 higher estimated BMD (or > 10% higher estimated BMD). None of the three genetic variants was associated with known risk factors for fracture or low BMD (P < 0.01). Serum alpha-tocopherol was not associated with the risk of fracture (odd ratio = 0.97, P = 0.48).

Data from this study suggests that alpha-tocopherol SNPs were associated with higher estimated BMD.  Researchers stated that their results agreed with other observational trials which found positive correlation between serum alpha-tocopherol and higher BMD. More research will be needed to verify these results.

Source: Michaëlsson, Karl, and Susanna C. Larsson. “Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study.” Nutrients 13, no. 6 (2021): 1940.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Posted August 30, 2021.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

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