HDL cholesterol and TaqIB cholesteryl ester transfer protein gene polymorphism in renal transplant recipients

Decreased serum levels of high-density lipoprotein cholesterol (HDL-C) are a well-known risk factor for coronary heart disease (CHD) in the general po pulation and have been suggested as one of the best predictor of CHD after renal transplantation. However, very heterogeneous HDL-C levels have been r eported in renal transplant recipients. In this patient population, serum H DL-C levels are determined by complex interactions between hormonal, enviro nmental (such as a high amount of abdominal adipose tissue), and genetic fa ctors and drugs (particularly glucocorticoids). We, therefore, evaluated th e effects of the cholesteryl ester transfer protein (CETP) gene TaqlB polym orphism as well as of abdominal obesity on HDL-C levels in 78 male renal tr ansplant recipients who were receiving azathioprine and/or ciclosporin A in combination with prednisone as immunosuppression. The patients were classi fied into genotypic groups according to the presence or absence of the rest riction site (B1 allele or B2 allele, respectively). The distribution of CE TP genotypes was similar to that previously described in the general popula tion. Overall, HDL-C levels were 19 and 26% higher in B1B2 and B2B2 patient s as compared with B1B1 homozygotes (p < 0.05), even after control for othe r lipid measurements. Patients with abdominal obesity (waist girth greater than or equal to 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, respe ctively, p < 0.01). Moreover, the HDL-C levels were markedly affected by th e CETP TaqlB polymorphism in lean patients (+28 and +41% in B1B2 and B2B2 a s 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 patie nts could be less susceptible to atherosclerosis than lean B1B1 homozygotes . In addition, patients with the B1B1 genotype had more documented CHD as c ompared with patients carrying at least one B2 allele, supporting the prote ctive effect of the B2 allele against CHD. In conclusion, considerable vari ation in HDL-C levels appears to be explained by the CETP TaqlB gene polymo rphism in male renal transplant recipients, but this potential protective g ene effect appears strong ly reduced by concomitant abdominal obesity. Copy right (C) 2000 S. Karger AG. Basel.