Hypertension and diabetes are both prevalent and morbid diseases. Though common among Caucasians, the modernization of agrarian societies appears to increase the incident rate among individuals with an Asian ethnic background. These disorders occur among the Chinese without obvious imposition of certain demographic """"""""markers"""""""" seen in the western societies, such as obesity. Thus, distinct genetic determinants may play important roles in the etiology of these diseases among Chinese. These unique genes, evolutionarily pivotal for survival under famine or other chronic hypocaloric nutritional conditions, are likely to be detrimental to health during adaption to modern society, where abundance of food and an affluent lifestyle prevail. A padigm of """"""""insulin resistance syndrome,"""""""" first described by Dr. Reaven as Syndrome X, provides an outstanding road map for investigation of pathophysiology (ies) of these diseases. The hypothesis of Syndrome X suggests that compensatory hyperinsulinemia occurs among individuals who are glucose intolerant, having a decreased ability to metabolize glucose despite abundant insulin (i.e., they are insulin resistant). The metabolic consequences of this hyperinsulinemia are increased blood pressure, dyslipidemia, and a cluster of other metabolic and vascular derangements. this is due to the chronic elevation of ambient plasma insulin concentrations, a hormone capable of initiating multiple metabolic and growth-related actions on many different target issues. Much evidence shows that insulin resistance is also a familial trait among other ethnic groups. To pursue the genetic component (s) of this paradigm, a large Chinese family study of hypertension, to be subset by insulin resistance phenotype, has been initiated. The study design uses stage II hypertensive patient as index case, seeking concordant or discordant sib-pairs, i.e., phenotyping hypertensive or hypotensive siblings. Insulin resistance is quantified by an insulin suppression test (IST). The steady state plasma glucose concentration (SSPG) at the end of a three-hour infusion of insulin, glucose and sandostatin is used as the index of insulin resisitance. Fasting lipids, and glucose and insulin responses to 75g oral glucose load are also determined, together with basic demographic characteristics such as BP, BMI, and W/H ratio. Systematic genotyping with random and candidate gene markers will be performed, and non-parametric quantitative trait linkage analysis used to define genetic loci statistically.
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