Bikunin and α₁-microglobulin/bikunin precursor (AMBP) gene mutational screening in patients with kidney stones: A case-control study

Abstract

Objective. Bikunin is an inhibitor of kidney stone formation synthesized in the liver together with α₁-microglobulin from the α₁-microglobulin/bikunin precursor (AMBP) gene. The aim of this study was to investigate the possible association between bikunin/AMBP gene polymorphisms and urinary stone formation. Material and methods. To analyse the DNA, blood samples were taken from 75 kidney stone formers who had a familial stone history, 35 sporadic stone formers and 101 healthy individuals. Four exons of bikunin gene and five parts of the promoter region of the AMBP gene were screened using single-strand conformation polymorphism and nucleotide sequence analysis. Results. The Init-2 region of the promoter of AMBP gene had polymorphisms at positions -218 and -189 nt giving three different genotypes having 1,3, 2,4 and 1,2,3,4 alleles with frequencies of 17.06%, 60.19% and 22.75%, respectively, in all groups. Therefore, the Init-2 region appears to be polymorphic. As a result, the 1,3 allele has -218G and -189T complying with the reference database sequence, the 2,4 allele has -218G and T-189C substitution and the allele 1,2,3,4 genotype has substitutions at positions G-218C and T-189C. Conclusions. There were no significant differences in allele distribution between patients and controls. These common alleles exist in the Turkish population independent of stone formation. These results are the first to demonstrate the existence of bikunin and AMBP promoter polymorphism. Although the Init-2 region of the AMBP gene is the binding site for various transcription factors, the results showed no association between these observed genotypes and stone-forming phenotypes.

Key Words::

• AMBP gene polymorphism
• bikunin gene
• kidney stone
• mutation screening

Acknowledgement

This study was supported by a research project (SBAG-2786, 104S370) from The Scientific and Technological Research Council of Turkey (TUBITAK).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.