Genetics, Lipids, and Responses to Exercise Training

描述（由申请方提供）：拟定研究将评估和表征可能与血浆脂蛋白脂质水平及其运动训练变化相关的LIPH和APOL 1新遗传变异。这项研究的假设是，LIPH和APOL 1的遗传变异，HDL代谢和组成的候选基因，将部分解释血浆HDL水平的变异性及其随运动训练的变化。该研究将在50-75岁的健康人群中采用标准化运动训练干预，进行基线和最终测试，包括血浆脂蛋白脂质的NMR测量，测序和筛选新鉴定的HDL代谢候选基因，在这些新鉴定的基因位点对受试者进行基因分型，并评估鉴定的变体与血浆脂蛋白脂质水平及其对运动训练的反应的潜在关联。申请人将准备进行机制研究，包括中间表型、mRNA表达和血蛋白水平研究，以验证发现的任何相关性。 她每年与Eric霍夫曼博士（华盛顿儿童国家医学中心遗传医学研究中心）一起接受两个月的培训，将训练她使用新兴的遗传和生化技术来支持她在马里兰州大学进行的最先进的遗传学运动生理学研究。

DESCRIPTION (provided by applicant): The proposed study will assess and characterize new genetic variants in LIPH and APOL1 that may relate to plasma lipoprotein lipid levels and their changes with exercise training. The study hypothesis is that genetic variants in LIPH and APOL1, candidate genes for HDL metabolism and composition, will partly explain the variability in plasma HDL levels and their changes with exercise training. The study will employ a standardized exercise training intervention in healthy 50-75 year olds, conduct baseline and final testing that includes NMR measurement of plasma lipoprotein lipids, sequence and screen newly identified candidate genes for HDL metabolism, genotype subjects at these newly identified gene loci, and assess the potential association of identified variants with plasma lipoprotein lipid levels and their responses to exercise training. The applicant will be prepared to perform mechanistic studies, including intermediate phenotype, mRNA expression, and blood protein level studies, to validate any associations found. The two months/yr she spends training with Dr. Eric Hoffman (Research Center for Genetic Medicine at Children's National Medical Center, Washington, DC) will train her to use emerging genetic and biochemical techniques to support her state-of-the-art genetics-exercise physiology research at the University of Maryland.