Table 2.
Gene symbol | Gene name | Evidence of genetic association | Ref. |
---|---|---|---|
ABCG8 | ATP-binding cassette, subfamily G (WHITE), member 8 | Was identified as a candidate gene for a mouse HDL QTL on Chromosome 17. Polymorphisms are associated with serum HDL levels in human subjects. Abcg8−/− mice have higher BMD. |
[85–88] |
| |||
APOE | apolipoprotein E |
Apoe−/− mice have increased BMD. Well-established genetic association with HDL in humans. Inconsistent association between APOE polymorphisms and BMD and fracture in humans. |
[38,79,89–93] |
| |||
ESR1 | estrogen receptor 1 (alpha) | Is one of two receptors for estrogen. Loss of estrogen at menopause is associated with increased osteoclast activity. Ers1 knockout male mice exhibit higher BMD and higher serum HDL levels. |
[36,94–96] |
| |||
GHRH | growth hormone releasing hormone | Signals for release of growth hormone. Growth hormone acts both directly and indirectly on bone. Patients with growth hormone deficiency have low levels of HDL and have low bone mass. Polymorphisms in the GHRH gene are associated with proximal femur and spinal BMD. |
[97–99] |
| |||
IL6 | interleukin 6 |
Il6−/− mice have decreased BMD. Polymorphisms associated with both HDL and BMD in human subjects. |
[100–108] |
| |||
MTHFR | 5,10-methylenetetrahydrofolate reductase | Mutations in this gene causes hyperhomocysteinemia, a risk factor for both CVD and osteoporosis. Polymorphisms in this gene are associated with both HDL and BMD in human subjects. |
[109–113] |
| |||
PON1 | paraoxonase 1 | Numerous studies have linked polymorphisms in this gene with HDL levels. Polymorphism in this gene may be associated with femoral neck and spine BMD in humans. Other studies have suggested no association with BMD, but association with fracture. |
[38,114,115] |
| |||
PPARG | peroxisome proliferator activated receptor gamma |
Pparg+/− mice have higher bone mass. Polymorphisms in PPARG interact with dietary fat to affect BMD in humans. The common C161T and Pro12Ala polymorphisms are associated with HDL levels in humans. |
[40,116–121 ] |
| |||
TNF | tumor necrosis factor |
Tnf−/− mice have increased bone mineral density. Polymorphisms in this gene are associated with both HDL and BMD in human subjects. |
[122–127] |