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- APOE, apolipoprotein E
- BMI, body mass index
- DXA, dual energy X-ray absorptiometry
- IBD, identity by descent
- LD, linkage disequilibrium
- LDL, low density lipoprotein
- PCR, polymerase chain reaction
- PFM, percentage fat mass
- QTDT, quantitative transmission disequilibrium test
- SNP, single nucleotide polymorphism
- TGF-β1, transforming growth factor beta 1
Obesity, defined as a body mass index (BMI) of greater than 30 kg/m2, has become a worldwide public health problem.1 About 250 million adults, roughly 7% of the world adult population, are considered obese and two or three times as many may be overweight with BMI of 25–30 kg/m2.2 A recent analysis shows that the health care cost of obesity is probably between 0.89% and 4.32% of the national expenditure in the United States.3 Obesity is associated with many diseases such as type 2 diabetes mellitus, hypertension, coronary heart disease, and certain forms of cancer.1 As a complex disease, obesity is determined by multiple genetic and environmental factors, including physiological, behavioural, and sociocultural factors.4–7 Numerous molecular genetics studies have been launched to search for the genes underlying the variations of obesity phenotypes, resulting in a host of candidate genes and potentially important genomic regions.8
Apolipoprotein E (APOE), coding a glycoprotein that plays a central role in lipid metabolism, is considered as a prominent candidate gene for obesity. APOE binds with high affinity to the low density lipoprotein (LDL) receptor and facilitates endocytosis of the associated lipoprotein particle.9 In addition, APOE mediates lipoprotein interactions with the LDL receptor related protein, very low-density lipoprotein receptor, and other lipoprotein receptors.9,10 Some studies have reported positive associations between APOE genotypes and some obesity phenotypes,11–14 whereas negative results were observed for the other obesity phenotypes.13–15 The transforming growth factor beta 1 (TGF-β1) gene codes a multifunctional cytokine that controls proliferation, differentiation, and other functions in many cell types, including adipocyte precursor cells.16 Increased TGF-β1 expression was associated with BMI and abdominal adipose tissue in morbid obesity.17 A recent study suggested an association between TGF-β1 polymorphism …
The study was partially supported by grants from Health Future Foundation of the USA, grants from the National Institute of Health (K01 AR02170–01, R01 GM60402–01 A1, P01 DC01813–07), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program (LB595) and the State of Nebraska Tobacco Settlement Fund (LB692), and a US Department of Energy grant (DE-FG03–00ER63000/A00).