Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Hum Genet. 2013 Apr;132(4):405-13. doi: 10.1007/s00439-012-1256-1. Epub 2012 Dec 22.
Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason for this is not clear. We aimed to examine whether there were additional genetic differences between racial/ethnic groups on lipoprotein profile. Genotypes were assessed using the Affymetrix 6.0 array in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Association analysis was conducted on fasting mean particle diameters using linear models, adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. Replication of associations reaching P < 1.97 × 10(-05) (the level at which we achieved at least 80% power to replicate SNP-phenotype associations) was conducted in the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA; N = 2,430). Variants which replicated across both Caucasian populations were subsequently tested for association in the African-American (N = 1,594), Chinese (N = 758), and Hispanic (N = 1,422) populations of MESA. Variants in the APOB gene region were significantly associated with mean VLDL diameter in GOLDN, and in the Caucasian and Hispanic populations of MESA, while variation in the hepatic lipase (LIPC) gene was associated with mean HDL diameter in both Caucasians populations only. Our findings suggest that the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of IR that are sensitive to race/ethnicity.
特定的脂蛋白颗粒特征组合，反映为平均脂蛋白颗粒直径的差异，与胰岛素抵抗（IR）和心血管疾病（CVD）的风险相关。脂质谱与疾病风险的关联因种族/民族而异，但原因尚不清楚。我们旨在研究种族/民族之间脂蛋白谱是否存在其他遗传差异。在遗传降脂药物和饮食网络（GOLDN）的 817 名相关白种人参与者中，使用 Affymetrix 6.0 阵列评估基因型。使用线性模型对空腹平均颗粒直径进行关联分析，调整年龄、性别和研究中心作为固定效应，以及谱系作为随机效应。在动脉粥样硬化多民族研究（MESA；N=2430）的白种人群中复制达到 P<1.97×10(-05)（我们达到至少 80%复制 SNP-表型关联的功效的水平）的关联。在 MESA 的非裔美国人（N=1594）、中国（N=758）和西班牙裔（N=1422）人群中，对跨两个白种人群复制的变体进行了关联测试。APOB 基因区域的变体与 GOLDN 中的平均 VLDL 直径以及 MESA 的白种人和西班牙裔人群中的平均 HDL 直径显著相关，而肝脂酶（LIPC）基因的变异仅与两个白种人群中的平均 HDL 直径相关。我们的研究结果表明，平均脂蛋白直径的遗传基础因种族/民族而异。由于脂蛋白直径是可调节的，这可能导致在降低 IR 期间针对种族/民族制定新的调节脂蛋白谱的策略。
