SLEEP-DISORDERED BREATHING & THE METABOLIC SYNDROME

描述（由申请人提供）： 睡眠呼吸障碍（SDB）和代谢综合征通常共存。与SDB相关的交感神经活动增加和神经内分泌变化可能有助于胰岛素抵抗和/或代谢综合征的其他组分的发展或恶化。或者，肥胖和内脏肥胖增加可能与代谢综合征和SBD有关。此外，代谢综合征和SDB都在家族中聚集，这两种情况可能有一些共同的遗传决定因素。该提案将检验以下假设：在非裔美国人中：1）SDB和代谢综合征具有共同的决定因素; 2）遗传因素有助于SDB和代谢综合征之间的关联。为了实现这一目标，我们将在参与胰岛素抵抗动脉粥样硬化家族研究（IRAS家族研究）的一个大型明确定义的非裔美国家庭队列中研究代谢综合征和SDB之间的相互关系，该研究是由NHLBI资助的一项正在进行的研究。在IRAS家族研究中，UCLA中心招募了34个大的非裔美国人家族，包括523名受试者，并提供了479个同胞对和1257个伯父对。在所有受试者中测量胰岛素敏感性和代谢综合征的其他组分，并进行全基因组扫描。将在400名受试者中使用多导睡眠图评估SDB，这将提供超过350对同胞和1，000对叔伯。我们还将重复测量这些受试者的代谢综合征组分，以便与SDB测量同时进行。具体目标是：1）在参与IRAS家族研究的非裔美国人家族中确定SDB与代谢综合征及其组分之间的关联; 2）确定SDB的遗传性以及共享基因、共享环境或两者对SDB与非裔美国人代谢综合征之间的关联的影响;和3）利用可用的基因组扫描，使用系统性连锁作图方法，确定可能导致SDB的人类基因组的候选区域以及SDB与非裔美国人的代谢综合征之间的关联。这项工作的成功将导致更好地了解这两种情况的相互作用和发病机制，并可能导致更好的预防和治疗方式。

DESCRIPTION (provided by applicant): Sleep-disordered breathing (SDB) and the metabolic syndrome commonly co-exist. It is possible that the increased sympathetic activity and neuroendocrine changes associated with SDB contribute to development or worsening of insulin resistance and/or other components of the metabolic syndrome. Alternatively, adiposity and increased visceral obesity could link the metabolic syndrome and SBD. Furthermore, both the metabolic syndrome and SDB aggregate in families, and these two conditions could share some genetic determinants. This proposal will test the hypotheses that in African Americans: 1) SDB and the metabolic syndrome share common determinants; and 2) genetic factors contribute to the association between SDB and the metabolic syndrome. To achieve this goal, we will examine inter-relationships between the metabolic syndrome and SDB in a large well-defined cohort of African American families participating in the Insulin Resistance Atherosclerosis Family Study (IRAS Family Study), an ongoing study funded by NHLBI. In the IRAS Family Study, the UCLA center recruited 34 large extended African American families comprising 523 subjects and providing 479 sib-pairs and 1257 avuncular pairs. Insulin sensitivity and other components of the metabolic syndrome were measured in all subjects and a genome-wide scan has been performed. SDB will be assessed with polysomnography in 400 subjects which will provide more than 350 sib-pairs and 1,000 avuncular pairs. We will also repeat measuring components of the metabolic syndrome in these subjects so that they will be concurrent with measures of SDB. The specific aims are to: 1) Determine the association between SDB and the metabolic syndrome and its components in African American families participating in the IRAS Family Study; 2) Determine the heritability of SDB and the effects of shared genes, shared environments, or both on the association between SDB and the metabolic syndrome in African Americans; and 3) Determine candidate regions of the human genome which could contribute to SDB and the association between SDB and the metabolic syndrome in African Americans using a systemic linkage mapping approach utilizing the available genome scan. Success of this work will lead to better understanding of the interaction and the pathogenesis of the two conditions and could lead to better preventive and therapeutic modalities.