Assessment of the polymorphic SACII and DDEI sites in the 5' flanking region of the human cystatin C gene in Egyptian patients

ABSTRACT

Cystatin C is a cysteine proteinase inhibitor with widespread distribution in body fluids and tissues. Physiologically relevant polymorphisms have been identified in the promoter region and the signal peptide of the cystatin C gene. However, the final importance of cystatin C polymorphisms in human diseases is still discussed controversially and the prognostic value in different conditions is unknown. In this study, in order to assess the significance of the polymorphic genotypes at positions -82, -5 and +4 of the 5' flanking region of the CST3 gene in case of heart, kidney and/or diabetic disorders in Egyptian patients, we compared frequencies of these polymorphisms in various groups of Egyptian patients with different conditions and controls. Genotyping analysis of all subjects revealed that these polymorphisms are in strong-linkage disequilibrium. Notably, no statistically significant differences in the allele or haplotype frequencies were observed for the investigated polymorphisms between patient and control groups. Moreover, haplotype differences within each group had no visible impact on plasma cystatin C levels which were significantly elevated for all groups compared to the control group. The observed elevation in cystatin C levels was probably a reflection of reduced glomerular filtration rate in these patients. Finally, our results suggest that in this population the haplotype alone was not associated with prognosis and that other, unknown environmental or genetic, factors may be of relevance