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HDL cholesterol and TaqIB cholesteryl ester transfer protein gene polymorphism in renal transplant recipients
1Lipid Research Center, Centre Hospitalier Universitaire de Québec, Qué., Canada.
Insights
High-density lipoprotein cholesterol (HDL-C) levels vary significantly in male renal transplant recipients due to cholesteryl ester transfer protein (CETP) gene polymorphism. Abdominal obesity diminishes the protective effect of the B2 allele on HDL-C levels and coronary heart disease (CHD) risk.
Area of Science:
- Cardiovascular Genetics
- Transplantation Medicine
- Lipid Metabolism
Background:
- Decreased high-density lipoprotein cholesterol (HDL-C) is a significant risk factor for coronary heart disease (CHD), particularly post-renal transplantation.
- HDL-C levels exhibit considerable heterogeneity in renal transplant recipients due to complex genetic, hormonal, environmental, and drug-related factors.
- The cholesteryl ester transfer protein (CETP) gene TaqIB polymorphism and abdominal obesity are potential modulators of HDL-C levels.
Purpose of the Study:
- To investigate the influence of CETP gene TaqIB polymorphism and abdominal obesity on HDL-C levels in male renal transplant recipients.
- To assess the combined effects of genetic variations and abdominal adiposity on cardiovascular risk markers in this patient cohort.
Main Methods:
- Genotyping of CETP TaqIB polymorphism (B1 and B2 alleles) in 78 male renal transplant recipients.
- Measurement of serum HDL-C levels and assessment of abdominal obesity via waist girth.
- Statistical analysis to determine the impact of genotypes and obesity on HDL-C and total cholesterol:HDL-C ratio.
Main Results:
- HDL-C levels were significantly higher in patients with B1B2 and B2B2 genotypes compared to B1B1 homozygotes.
- Abdominal obesity was associated with significantly reduced HDL-C levels.
- The CETP TaqIB polymorphism significantly affected HDL-C levels in lean patients, but this effect was diminished in obese patients.
- Lean patients with the B2B2 genotype showed lower total cholesterol:HDL-C ratios, suggesting reduced atherosclerosis susceptibility.
- The B1B1 genotype was associated with a higher incidence of documented CHD compared to genotypes with at least one B2 allele.
Conclusions:
- CETP TaqIB gene polymorphism significantly contributes to HDL-C level variations in male renal transplant recipients.
- Abdominal obesity substantially attenuates the potentially protective effects of the CETP B2 allele on HDL-C levels and CHD risk.
- These findings highlight the interplay between genetic predisposition and environmental factors in cardiovascular risk management post-transplantation.
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.