Variation in GYS1 Interacts with Exercise and Gender to Predict Cardiovascular Mortality
نویسندگان
چکیده
BACKGROUND The muscle glycogen synthase gene (GYS1) has been associated with type 2 diabetes (T2D), the metabolic syndrome (MetS), male myocardial infarction and a defective increase in muscle glycogen synthase protein in response to exercise. We addressed the questions whether polymorphism in GYS1 can predict cardiovascular (CV) mortality in a high-risk population, if this risk is influenced by gender or physical activity, and if the association is independent of genetic variation in nearby apolipoprotein E gene (APOE). METHODOLOGY/PRINCIPAL FINDINGS Polymorphisms in GYS1 (XbaIC>T) and APOE (-219G>T, epsilon2/epsilon3/epsilon4) were genotyped in 4,654 subjects participating in the Botnia T2D-family study and followed for a median of eight years. Mortality analyses were performed using Cox proportional-hazards regression. During the follow-up period, 749 individuals died, 409 due to CV causes. In males the GYS1 XbaI T-allele (hazard ratio (HR) 1.9 [1.2-2.9]), T2D (2.5 [1.7-3.8]), earlier CV events (1.7 [1.2-2.5]), physical inactivity (1.9 [1.2-2.9]) and smoking (1.5 [1.0-2.3]) predicted CV mortality. The GYS1 XbaI T-allele predicted CV mortality particularly in physically active males (HR 1.7 [1.3-2.0]). Association of GYS1 with CV mortality was independent of APOE (219TT/epsilon4), which by its own exerted an effect on CV mortality risk in females (2.9 [1.9-4.4]). Other independent predictors of CV mortality in females were fasting plasma glucose (1.2 [1.1-1.2]), high body mass index (BMI) (1.0 [1.0-1.1]), hypertension (1.9 [1.2-3.1]), earlier CV events (1.9 [1.3-2.8]) and physical inactivity (1.9 [1.2-2.8]). CONCLUSIONS/SIGNIFICANCE Polymorphisms in GYS1 and APOE predict CV mortality in T2D families in a gender-specific fashion and independently of each other. Physical exercise seems to unmask the effect associated with the GYS1 polymorphism, rendering carriers of the variant allele less susceptible to the protective effect of exercise on the risk of CV death, which finding could be compatible with a previous demonstration of defective increase in the glycogen synthase protein in carriers of this polymorphism.
منابع مشابه
A study of variation in cardiocirculatory parameters with different body positions during isometric exercise in young adult males.
Introduction: To study the effects of exercise, how important it is to choose a posture? We aimed to characterize the possible impact of different body positions on cardiovascular parameters during and after sustained isometric handgrip (IHG) exercise. Materials and Methods: Cross sectional study was carried out in 33 young adult males (mean age: 19.21±1.083 years). We recorded Bloo...
متن کاملThe Effect of Exercise on Paraoxonase-1 Activity and Lipid Profile in Obesity and Insulin Resistance Conditions
In the absence of insulin, regular physical activity facilitates the glucose entry into the cell via affecting several signaling pathways. Moreover, regular exercise improves the lipid profile and increases the paraoxonase-1 (PON-1) activity. PON-1 interacts with High-density lipoprotein (HDL) and, in the presence of calcium, hydrolyzes free radicals, prevents low-density lipoprotein (LDL) oxid...
متن کاملExploratory analysis of PM2.5 variation trend of Tehran, Iran, in various time series and its relation with cardiovascular mortality rate using R software
Among the numerous air pollutants, the strongest proof for adverse health effects has been reported for particulate matter (PM). The aim of this study was the exploration of short-term associations of air pollution with mortalities due to cardiovascular diseases (CVD) in Tehran, Iran, based on hospital and census data from 2007 to 2013. This descriptive and analytical research was conducted in ...
متن کاملExploring the effect of broccoli on some cardiovascular risk factors and insulin resistance with combined aerobic-resistance exercise training in men with type 2 diabetes
Introduction: Diabetes is one of the leading causes of mortality in developing countries. The aim of this study was to investigate The effect of broccoli powder supplementation along with combined exercise training on some cardiovascular risk factors and insulin resistance in men with type 2 diabetes. Materials and Methods: For this purpose, 44 volunteer diabetic men after homogenization ba...
متن کاملThe effect of twelve weeks of aerobic interval training on liver complications and cardiovascular risk factors in men with type 2 diabetes
Background & Aims: One of the main complications of type 2 diabetes is cardiovascular complications, which greatly increases mortality and reduces the quality of life of these patients. Complications of type 2 diabetes, which are known as cardiovascular risk factors, include dyslipidemia (1, 3) and high blood pressure, which are common diseases in type 2 diabetes (1, 4). Another complication of...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- PLoS ONE
دوره 2 شماره
صفحات -
تاریخ انتشار 2007