HDL Cholesterol and TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism in Renal Transplant Recipients

Abstract

Decreased serum levels of high-density lipoprotein cholesterol (HDL-C) are a well-known risk factor for coronary heart disease (CHD) in the general population and have been suggested as one of the best predictor of CHD after renal transplantation. However, very heterogeneous HDL-C levels have been reported in renal transplant recipients. In this patient population, serum HDL-C levels are determined by complex interactions between hormonal, environmental (such as a high amount of abdominal adipose tissue), and genetic factors and drugs (particularly glucocorticoids). We, therefore, evaluated the effects of the cholesteryl ester transfer protein (CETP) gene TaqIB polymorphism as well as of abdominal obesity on HDL-C levels in 78 male renal transplant recipients who were receiving azathioprine and/or ciclosporin A in combination with prednisone as immunosuppression. The patients were classified into genotypic groups according to the presence or absence of the restriction site (B1 allele or B2 allele, respectively). The distribution of CETP genotypes was similar to that previously described in the general population. Overall, HDL-C levels were 19 and 26% higher in B1B2 and B2B2 patients as compared with B1B1 homozygotes (p < 0.05), even after control for other lipid measurements. Patients with abdominal obesity (waist girth ≧93 cm) showed reduced HDL-C levels as compared with lean (waist girth <93 cm) patients (1.20 ± 0.28 vs. 1.42 ± 0.41 mmol/l, respectively, p < 0.01). Moreover, the HDL-C levels were markedly affected by the CETP TaqIB polymorphism in lean patients (+28 and +41% in B1B2 and B2B2 as compared with B1B1 patients, p < 0.05), but no significant difference was observed among obese patients. Significantly lower total cholesterol:HDL-C ratios were obtained in lean B2B2 homozygotes, suggesting that these patients could be less susceptible to atherosclerosis than lean B1B1 homozygotes. In addition, patients with the B1B1 genotype had more documented CHD as compared with patients carrying at least one B2 allele, supporting the protective effect of the B2 allele against CHD. In conclusion, considerable variation in HDL-C levels appears to be explained by the CETP TaqIB gene polymorphism in male renal transplant recipients, but this potential protective gene effect appears strongly reduced by concomitant abdominal obesity.