Matrix GLA protein gene polymorphism in kidney stone forming patients

Stone formation is a process, includes crystal nucleation, growth, aggregation, and crystal retention within the renal tubules. Urine contains various macromolecules that modulate this process and protect the kidney against stone formation. Matrix Gla protein (MGP) appears to be an important protective modulator against crystallization since it is a potential inhibitor of tissue calcification. In this respect, it is aimed to establish the relationship between the distributions of nucleotide alterations found in promoter and coding regions of MGP gene in patients with kidney stone and normal individuals. DNA samples were obtained from 88 familial kidney stone formers, 111 sporadic stone formers, and from 94 healthy individuals, respectively. The DNA samples obtained were analyzed by Polymerase Chain Reaction (PCR) method using the 3 sets of primer pairs which cover the coding (Thr83Ala in exon 4) and promoter regions (T-138C and G-7A) of MGP gene. Amplified regions were analyzed by Restriction Fragment Length Polymorphism (RFLP) method for possible polymorphisms. The chi-square analysis of the results revealed that there is no relationship between the observed polymorphisms and stone formation. However, each of three polymorhisms evaluated by Hardy-Weinberg equilibrium (HWE) revealed that G-7A genotype has no relation with the stone formation. The T-138C polymorphisms has shown deviation both in stone formers and the control group suggesting that this polymorphism is noninformative for stone formation risk while the Thr83Ala polymorphism has shown the significance only in stone formers suggesting the possible candidate region for stone formation. Additionally, haplotype analysis revealed that two haplotype blocks (T-A-Thr and C-A-Ala) are related with stone formation risk. In conclusion, either the polymorphic nature of the genes invoved in macromoleculer mechanism or their expressional level develops the risk of stone formation.