Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

<p>Abstract</p> <p>Background</p> <p>The identification of genetic variants related to blood lipid levels within a large, population-based and nationally representative study might lead to a better understanding of the genetic contribution to serum lipid levels in the major race/ethnic groups in the U.S. population.</p> <p>Methods</p> <p>Using data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), we examined associations between 22 polymorphisms in 13 candidate genes and four serum lipids: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). Univariate and multivariable linear regression and within-gene haplotype trend regression were used to test for genetic associations assuming an additive mode of inheritance for each of the three major race/ethnic groups in the United States (non-Hispanic white, non-Hispanic black, and Mexican American).</p> <p>Results</p> <p>Variants within <it>APOE </it>(rs7412, rs429358), <it>PON1 </it>(rs854560), <it>ITGB3 </it>(rs5918), and <it>NOS3 </it>(rs2070744) were found to be associated with one or more blood lipids in at least one race/ethnic group in crude and adjusted analyses. In non-Hispanic whites, no individual polymorphisms were associated with any lipid trait. However, the <it>PON1 </it>A-G haplotype was significantly associated with LDL-C and TC. In non-Hispanic blacks, <it>APOE </it>variant rs7412 and haplotype T-T were strongly associated with LDL-C and TC; whereas, rs5918 of <it>ITGB3 </it>was significantly associated with TG. Several variants and haplotypes of three genes were significantly related to lipids in Mexican Americans: <it>PON1 </it>in relation to HDL-C; <it>APOE </it>and <it>NOS3 </it>in relation to LDL-C; and <it>APOE </it>in relation to TC.</p> <p>Conclusions</p> <p>We report the significant associations of blood lipids with variants and haplotypes in <it>APOE</it>, <it>ITGB3, NOS3</it>, and <it>PON1 </it>in the three main race/ethnic groups in the U.S. population using a large, nationally representative and population-based sample survey. Results from our study contribute to a growing body of literature identifying key determinants of plasma lipoprotein concentrations and could provide insight into the biological mechanisms underlying serum lipid and cholesterol concentrations.</p