Genetic analysis of CVD risk factors

描述（由申请人提供）： 项目1的目标是检测、映射和表征多态性 这些基因导致心血管疾病（CVD）风险的变化。 该计划项目的重点（圣安东尼奥家庭壁炉研究，SAFHS） 是墨西哥裔美国人的大家庭， status.在目前的补助金期间，每个家庭成员都在进行基因分型 414个短串联重复序列标记。使用基因组 筛选来自前十个基因分型家族的数据（谱系集A， 500个个体），已经检测并定位了影响瘦素的QTL， 脂肪量、BMI、胰岛素、2小时葡萄糖、LDL-3-C、HDL-C、未酯化HDL 2a 胆固醇，连锁证据，额外的，更紧密的标记物 被用于更精细的地图绘制策略。鉴定 这些基因中最具特征的几个基因的功能等位基因将 在项目3中进行。 在项目1中，利用家庭资源， 基因型和表型数据是在过去十年中创建的， 将对表现出实质性的表型进行连锁分析。 遗传力，但没有检测到显着的联系， 谱系集合A（例如，载脂蛋白，选择的脂蛋白大小类别， 空腹血糖、2小时胰岛素、纤维蛋白原、C反应蛋白和测量 颈动脉内膜中层厚度）。联动信号也将得到加强 并对其他QTL进行了细化，对于这些QTL，已经有显著的连锁证据， 已经被检测到（例如，17号染色体上的BMI QTL，染色体上的HDL-C QTL 16、3号染色体上的胰岛素/葡萄糖比率和HDL 2a未酯化胆固醇 在染色体8上）。这些分析将纳入其他标志物， 将寻找与位置候选基因中多态性的关联。 与脂肪组织作为内分泌系统的作用有关的几种新的表型 将检查器官，并检测QTL的多效性效应， 目前和拟议的赠款期间，对其他CVD风险因素将是 表征了 在SAFHS中为家庭积累的纵向数据将是 用于研究遗传对CVD风险中年龄相关变化的影响。

DESCRIPTION (provided by the applicant): The objective of Project 1 is to detect, map and characterize polymorphic genes that contribute to variation in risk of cardiovascular disease (CVD). The focus in this Program Project (the San Antonio Family Hearth Study, SAFHS) is on extended Mexican American families ascertained without regard to disease status. During the current grant period each family member is being genotyped for 414 short tandem repeat markers in a 10 centimorgan map. Using genome screen data from the first ten genotyped families (Pedigree Set A, with nearly 500 individuals), QTLs have been detected and mapped that influence leptin, fat mass, BMI, insulin, 2 hour glucose, LDL-3-C, HDL-C, HDL2a unesterified cholesterol, evidence for linkage, additional, more closely spaced markers are being typed for use in finer scale mapping strategies. Identification of the functional alleles for a few of the best characterized of these genes will be pursued in Project 3. In Project 1, taking advantage of the resource of families with extensive genotypic and phenotypic data that has been created in the past ten years, linkage analyses will be pursued for phenotypes that exhibit substantial heritabilities but for which significant linkages were not detected in Pedigree Set A (e.g., apolipoproteins, selected lipoproteins size classes, fasting glucose, 2-hour insulin, fibrinogen, C-reactive protein, and measures of carotid intima-media thickness). Linkage signals also will be strengthened and refined for other QTLs for which significant evidence of linkage already has been detected (e.g., QTLs for BMI on chromosome 17, HDL-C on chromosome 16, insulin/glucose ratio on chromosome 3, and HDL2a unesterfied cholesterol on chromosome 8). These analyses will incorporate additional markers, and associations will be sought with polymorphisms in positional candidate genes. Several new phenotypes related to the role of adipose tissue as an endocrine organ will be examined, and the pleiotropic effects of QTLs detected in the current and proposed grant periods, on other CVD risk factors will be characterized. The longitudinal data being accumulated for the families in the SAFHS will be exploited to examine genetic effects on age-related changes in CVD risk.