Impact of the fetuin gene polymorphisms in coronary artery calcification and mortality of patients with chronic kidney disease and renal transplant

Abstract

Fetuin A is a major systemic inhibitor of vascular calcifications. The aim of this study was to examine association of single nucleotide polymorphisms (SNP) in the gene for fetuin-A with fetuin-A serum levels, coronary arteries calcification (CAC) and mortality in renal transplant (RT) and chronic kidney (CKD) patients. This study included 88 patients (42 stable RT patients at least 6 months after transplantation and 46 CKD patients, stage 2-5 not requiring dialysis) followed five years. Detection and analysis of fetuin A gene polymorphisms in positions C742T (Thr248Met; rs4917) and C766G (Thr256Ser; rs4918) were performed using PCR method. Respondents with allele 742T had at the same time 766G. Combined genotypes TT/GG had lower serum fetuin A levels than CT /CG and CC/CC. Predictors of CAC in univariate analysis were age (p=0,000), serum fetuin-A levels (p=0.011) and rs 4917 polymorphism (p=0.021) while multivariate determined age (p=0.001) and fetuin-A levels (p=0.031). Patients who were homozygous for variant 742T and 766G (combined genotype TT/GG) had lowest survival rate. Our results suggest that allele 742T and 766G in gene for fetuin-A were associated with lower serum fetuin-A levels, higher CAC occurrence and higher mortality rate in RT and CKD patients.