Table 2.

Genes associated with both HDL and BMD.

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]