Cholesterol ester transfer protein (CETP) facilitates reverse cholesterol transport via HDL-C and this activity may be increased in obese subjects. In normal weight subjects the Taq1B variant of the CETP gene is associated with lower CETP activity and higher HDL-C. The aim of this study was to examine the relationship between the Taq1B polymorphism and HDL-C in obese women before and after weight loss. A total of 245 women (41 with type 2 diabetes) were genotyped for the Taq1B variant. Plasma lipids, insulin, glucose and oral glucose tolerance were also measured before and after weight loss. When all subjects were examined together the Taq1B genotype was not associated with HDL-C. However, when non-diabetic subjects were divided by median fasting insulin, a strong linear association was observed between Taq1B genotype and HDL-C in subjects below median for fasting insulin (B1B1 1.19+/-0.07 mmol/l, B1B2 1.35+/-0.06, B2B2 1.71+/-0.09, P