Study On The Relationship Between The Variation Of Anion Transporters Related Gene In Kidney And The Risk Of Kidney Stones

Kidney stones disease is a common and multiple complex disease with a high recurrence rate which is caused by genetic factors,dietary environment and other factors.The pathological mechanism of kidney stones disease is still unclear yet.At the mean time,the effective prevention and treatment methods of kidney stones disease are also insufficient.Calcium oxalate stones are the most common types of kidney stones which accounting for more than 80% of all types.Oxalic acid is a common metabolite in the organism,which can reduce the bioavailability of mineral elements and is easy to combine with calcium ions in the human body to form calcium oxalate which may easily cause kidney stone disease.The pyrophosphate in urine is an important inhibitor of forming crystal by reducing the supersaturated state of calcium and phosphorus.It can be combined to the surface of calcium phosphate in the renal tubules in order to avoid forming crystal.SLC26A6 protein is a multifunctional anions transport protein which especially plays an important role in transporting oxalic acid anions.ANKH protein is an inorganic pyrophosphate transport protein which could expressed in kidney and transport pyrophosphate to renal tubules and renal interstitial on the cavity surface and base surface of the manifolds.We speculated that the two proteins may play an important role in the process of formation of kidney stones.In the present study,we investigated the relationship between SNPs in SLC26A6 and ANKH gene and the risk of kidney stones disease by using the genome DNA in the blood of kidney stones patients and healthy people.Firstly,one nsSNP found in SLC26A6 and the 14 possible disease related SNPs found in ANKH were predicted by bioinformatics tools.All the predicted nsSNPs were then genotyped by allele-specific PCR and gene sequencing by using the extracted genomic DNA as PCR template.The genome DNA was extracted from the blood of kidney stones patients and healthy people with blood genomic DNA extraction kit.The results showed that the C allele of nsSNPrs184187143 in SLC26A6 gene of patients with kidney stones was significantly higher than the healthy people who had no history of kidney stones or family history of stone disease(OR 6.1,95% CI 1.36-27.38,p=0.007).The SNPs in ANKH gene had no obvious relationship with the risk of calcium oxalate kidney stone disease in the Northeast of China.Finally,we further investigated the molecular mechanism how could the nsSNP rs184187143 in SLC26A6 gene rise the risk of kidney stones diseases by using molecular dynamics method.Results shows that the alleles change of G to C(cause the amino acid change from glycine to arginine)of nsSNP rs184187143 in SLC26A6 gene may affected the transport function of oxalic acid ion by influencing the secondary structure of protein,which is associated with the risk of kidney stones.In summary,our study for the first time proved that SLC26A6 gene polymorphism mutation nsSNP rs184187143 has impact on the incidence of calcium oxalate kidney stones in Northeastern Chinese Han race,suggesting that the abnormity of oxalate transportation may contribute to the formation of kidney stones.The research provides a new train of thought on the study of the complicated molecular mechanisms of kidney stone disease.