Abstract 369: The Mechanisms of the Onset and Development of Dyslipidemia May Be Different Between Nonobese and Obese, Normotensive Individuals

Abstract

Background: We have previously reported the strong linkage of β2-adrenoceptor (ADRB2) polymorphisms to the onset and development of obesity, hypertension and insulin resistance (IR), which are a part of a criteria of metabolic syndrome (MetS). Objective: To clarify the effects of ADRB2 polymorphisms on the onset of dyslipidemia, another criteria of MetS, we evaluated the relationships between ADRB2 polymorphisms and deterioration of lipid metabolism in normotensives with a longitudinal study of 5 years. In addition, we compared the mechanisms of the onset of dyslipidemia between nonobese and obese subjects. Methods: In 329 normotensive men including 206 nonobese and 123 overweight/obese men, we measured BMI, BP, fasting glucose, insulin, total cholesterol (Tch), HDLch, LDL+VLDLch, triglycerides (TG) and plasma norepinephrine (NE) annually over 5 years. Subjects who had a significant change (≥10%) over 5 yrs in BP or BMI were excluded. The ADRB2 polymorphisms (Arg16Gly) were determined. Results: Significant increases in HOMA (≥10%) was noted in 24 (11.7%) nonobese and 22 (17.9%) obese subjects (nonobese vs obese, P<0.05). Significant increases in Tch, TG, LDL+VLDL or decreases in HDL were observed in 34, 38, 39, and 28 subjects, respectively. All subjects with deterioration in lipids showed increases in HOMA, and all subjects with significant increases in HOMA had deterioration in lipids. In nonobese subjects, subjects with deterioration in lipids and IR had greater plasma NE at entry and NE elevations over 5 yrs, whereas in obese subjects only greater NE elevations were observed in those with deterioration in lipids, but entry NE were similar. The frequencies of Gly16 allele were significantly higher in subjects with deteriorations in lipids. Lipids and HOMA at entry were similar between subjects with and without Gly16 allele, but increases in lipids and HOMA were greater in those with Gly16 allele. Conclusions: The Gly16 allele of ADRB2 polymorphism is associated with deterioration of lipid metabolism accompanied by increased HOMA and plasma NE. There may be different contributions of IR and sympathetic activity to the onset and development of dyslipidemia between nonobese and obese individuals.