Gene by environment interactions between three candidate genes for obesity and omega-3 polyunsaturated fatty acids

Thesis (M.S.) University of Alaska Fairbanks, 2008Multi-factorial diseases, like obesity, are caused by genetic and environmental factors. Few studies examine potential interactions between genetic and environmental factors. Understanding these interactions can lead to better disease prevention. One important environmental factor related to obesity is omega-3 fatty acids. Yup’ik Eskimos consume a high amount of two omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study examined 10 single nucleotide polymorphisms (SNPs) in three genes: ADIPOQ, PPARG, and PPARGC1A. Also, 7 obesity phenotypes were examined: BMI, percent body fat, waist circumference, sum of skin-folds, plasma adiponectin, plasma triglycerides, and HDL cholesterol. Associations between these SNPs and phenotypes in 981 related Yup’ik Eskimos were examined using mixed models. Interactions were investigated with these SNPs and δ15N, a biomarker used to determine intake of EPA and DHA. The results showed that EPA and DHA modify the expression of all three genes. Additionally, SNPs in all three genes were associated with one or more obesity phenotypes. The most statistically significant results were with two SNPs in ADIPOQ and plasma adiponectin. This study supports the role of these genes in the etiology of obesity. Finally, this study demonstrates that these genes are influenced by EPA and DHA