Proinflammatory status, genetics and atherosclerosis.

Over the last decade, C-reactive protein concentration analyzed by the high sensitivity method (hsCRP) has been proven as a marker of premature atherosclerosis. Concentration exceeding 2 mg/l represents an increased individual risk of myocardial infarction and stroke but strict application of this borderline is complicated by relations of CRP concentrations to other risk factors of cardiovascular diseases. In a large 1 % representative sample of the Czech population, a positive relation of hsCRP to BMI, a waist circumference and triglyceride concentration was documented. Substantial sex differences were found in its relationship to age. Whereas it is continuously increasing in men, this increase appears in women only after menopause. A substantial decrease of body weight and visceral fat volume by increased physical activity is accompanied by significant decrease of hsCRP in young obese women. This decrease was not related to a change of interleukin-6 concentration, although it is supposed to regulate CRP production. CRP concentration is partly under genetic control as a higher concentration in young siblings of probands with proved coronary atherosclerosis was documented. The participation of genes related to lipoprotein metabolism (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP concentrations. We hypothesized that an increased concentration of hsCRP represents a certain marker of proinflammatory status related to central obesity and triglyceride metabolism and it might be related to individual properties of monocytes in atherogenesis.

Changes of plasma lipids during weight reduction in females depends on APOA5 variants.

BACKGROUND: Apolipoprotein A5 (APOA5) is a determinant of plasma lipids, and its role in body mass index (BMI) determination is discussed. This study was aimed at the investigation of the relationship between common APOA5 gene variants and body weight/plasma lipid decrease in overweight females. METHODS: We analyzed 98 unrelated overweight and obese nondiabetic Czech females (BMI >27.5). APOA5 T-1131-->C and Ser19-->Trp variants were genotyped. Before and after 9 weeks of lifestyle modification, biochemical and anthropometrical measurements and assessment of nutritional intake were performed. The lifestyle modification program consisted of a reduction in energy intake and an exercise program (aerobic exercise 4 times per week, 60 min each). RESULTS: The mean age of the participants was 30.7 +/- 3.7 years, the mean BMI before the intervention was 31.4 +/- 3.8 and the weight loss was 5.9 +/- 2.5 kg (7 +/- 3%). There were 86 T-1131T homozygotes and 12 carriers of the C-1131 allele and 82 Ser19Ser homozygotes and 16 carriers of the Trp19 allele, respectively; 72 females had the commonest T-1131T/Ser19Ser haplotype. No significant association between BMI decrease and APOA5 variants was found, but T-1131T carriers have a significantly higher body weight both before and after the intervention (p < 0.05; p = not significant for BMI). The fasting glycemia was significantly higher in Trp19 carriers both before and after the intervention (p < 0.01). Further, plasma triglyceride levels decreased in Ser19Ser homozygotes but increased in Trp19 carriers (1.42 +/- 0.62 to 1.28 +/- 0.48 vs. 1.15 +/- 0.47 to 1.41 +/- 0.80 mmol/l; p < 0.05 for differences between the groups). Similarly, in carriers of at least 1 less common APOA5 allele (n = 26), plasma low-density lipoprotein cholesterol levels did not decrease as they did in T-1131T/Ser19Ser carriers (3.11 +/- 0.70 to 3.27 +/- 0.81 vs. 3.39 +/- 0.81 to 3.16 +/- 0.86 mmol/l; p < 0.05 for differences between the groups). CONCLUSIONS: APOA5 gene variants have effects on the decrease in plasma triglyceride and low-density lipoprotein cholesterol level in females in a model combining their dietary habits and physical activity changes.