National Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA, USA.
BMC Med Genet. 2010 Apr 20;11:62. doi: 10.1186/1471-2350-11-62.
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.
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).
Variants within APOE (rs7412, rs429358), PON1 (rs854560), ITGB3 (rs5918), and NOS3 (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 PON1 A-G haplotype was significantly associated with LDL-C and TC. In non-Hispanic blacks, APOE variant rs7412 and haplotype T-T were strongly associated with LDL-C and TC; whereas, rs5918 of ITGB3 was significantly associated with TG. Several variants and haplotypes of three genes were significantly related to lipids in Mexican Americans: PON1 in relation to HDL-C; APOE and NOS3 in relation to LDL-C; and APOE in relation to TC.
We report the significant associations of blood lipids with variants and haplotypes in APOE, ITGB3, NOS3, and PON1 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.
在一项大型的、基于人群且具有全国代表性的研究中，鉴定与血脂水平相关的遗传变异可能有助于更好地理解美国主要种族/族裔人群中血清脂质的遗传贡献。
利用来自第三次国家健康和营养检查调查（NHANES III）第二期（1991-1994 年）的数据，我们检验了 13 个候选基因中的 22 个多态性与四种血清脂质（高密度脂蛋白胆固醇[HDL-C]、低密度脂蛋白胆固醇[LDL-C]、总胆固醇[TC]和甘油三酯[TG]）之间的关联。采用单变量和多变量线性回归以及基因内单体型趋势回归，假设美国三个主要种族/族裔群体（非西班牙裔白人、非西班牙裔黑人、墨西哥裔美国人）的每种遗传模式均为加性模式，检验遗传相关性。
APOE（rs7412、rs429358）、PON1（rs854560）、ITGB3（rs5918）和 NOS3（rs2070744）内的变异在未经调整和调整分析中均与至少一个种族/族裔群体的一种或多种血液脂质相关。在非西班牙裔白人群体中，没有个体多态性与任何脂质特征相关。然而，PON1 的 A-G 单体型与 LDL-C 和 TC 显著相关。在非西班牙裔黑人群体中，APOE 变异 rs7412 和单体型 T-T 与 LDL-C 和 TC 强烈相关；而 ITGB3 的 rs5918 与 TG 显著相关。在墨西哥裔美国人中，三个基因的几个变异和单体型与脂质显著相关：PON1 与 HDL-C 相关；APOE 和 NOS3 与 LDL-C 相关；APOE 与 TC 相关。
我们使用大型的、具有全国代表性的基于人群的样本调查，报告了美国主要种族/族裔群体中 APOE、ITGB3、NOS3 和 PON1 内的血液脂质与变异和单体型的显著关联。我们的研究结果为确定血浆脂蛋白浓度的关键决定因素提供了更多的文献依据，并为血清脂质和胆固醇浓度的生物学机制提供了深入的了解。
