SLEEP-DISORDERED BREATHING & THE METABOLIC SYNDROME

点击翻译按钮获取中文摘要

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.