Mapping of FCHL-Related Atherogenic Traits

总体目标是了解风险因素的遗传基础，并确定其数量性状基因座。 心血管疾病，包括低密度脂蛋白密度、高密度脂蛋白水平和载脂蛋白B水平，以及PLTP活性 家族性混合性高脂血症(FCHL)。FCHL是导致早产的最常见的血脂紊乱 血管疾病。小而致密的低密度脂蛋白、低密度脂蛋白水平和高载脂蛋白水平是重要的 FCHL表型的致动脉粥样硬化成分。PLTP活性是一个重要的协变量。使用四个 大型FCHL家系将增加样本的同质性和协变量的联合考虑，包括 血浆脂蛋白转运蛋白的活性，将提高检测这些基因座连锁的能力。这些 调查认为患有FCHL的大家系和每个性状的孟德尔分离的证据， 世界卫生组织已经完成了10厘米的基因组扫描，从而可以有效地对这些 致动脉粥样硬化的FCHL相关表型。三个有显著连锁证据的基因座被确定为 使用IoD评分和较新的马尔科夫链蒙特卡罗调整低密度脂蛋白大小(最大颗粒直径) (MCMC)方法，分别对每个家系进行分析，并结合家系进行分析。USNG这些 对复杂性状的方法有望导致检测到高密度脂蛋白和高密度脂蛋白的显著关联证据 载脂蛋白B水平。随后将进行精细的图谱绘制和努力识别潜在的基因，从 具有低密度脂蛋白的大小/密度特征。作图，然后识别以前未检测到的这些性状的基因 将促进血脂紊乱的基础生物学和诊断、预防和治疗的可能性 血管疾病。

The overall goal is to understand the genetic basis of, and identify quantitative trait loci for, risk factorsfor cardiovascular disease including LDL density, HDL level, and apoB level, as well as PLTP activity, in families with familial combined hyperlipidemia (FCHL). FCHL is the most common lipid disorder leading to premature vascular disease. Small dense LDL, depressed HDL level, and elevated apoB level are important atherogenic components of the phenotype of FCHL. PLTP activity is an important covariate. Use of four large FCHL families will increase sample homogeneity and joint consideration of covariates, including plasma lipoprotein transfer protein activity, will improve power to detect linkage for these loci. These investigations consider large families with FCHL and evidence of Mendelian segregation of each trait, for whom a 10 cM genomic scan has already been completed, allowing efficient mapping studies of these atherogenic FCHL-related phenotypes. Three loci with significant evidence of linkage were identified for adjusted LDL size (peak particle diameter), using both Iod score and newer Markov chain Monte Carlo (MCMC) methods in analyses of both each family separately and the families combined. Usng these methods for complex traits is expected to result in detection of significant linkage evidence for HDL and apoB level. These will be followed by fine mapping and efforts to identify the underlying genes, beginning with LDL size/density traits. Mapping followed by identification of previously undetected genes for these traits will advance both the basic biology of lipid disorders and the potential to diagnose, prevent, and treat vascular disease.