Single Nucleotide Polymorphisms ( SNPs ) of URAT 1 ( rs 7932775 ) and ABCG 2 ( rs 3825016 ) on Chronic Kidney Disease Patients with Hyperuricemia

Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is How to cite this paper: Li, C.Q., Tang, Q., Jiang, H.W., Wu, J., Zhang, J.L., Yuan, F.L., Du, Y. and Du, H.C. (2018) Single Nucleotide Polymorphisms (SNPs) of URAT1 (rs7932775) and ABCG2 (rs3825016) on Chronic Kidney Disease Patients with Hyperuricemia. Chinese Medicine, 9, 118-125. https://doi.org/10.4236/cm.2018.93007 Received: July 2, 2018 Accepted: July 30, 2018 Published: August 2, 2018 Copyright © 2018 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia.As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases [1].Hyperuricaemia and gout correlate with both these diseases [2] [3].So those treatments which may lower serial uria and acute episode of gout can prevent and delay both cardiovascular diseases (CVD) and chronic kidney diseases [4].Genetic variation of key enzymes of purine metabolism and urate transporter is closely related with occurrence and development of hyperuricaemia and gout [5] [6].Genome-wide association studies (GWAS) have identified nearly 30 loci associated with urate concentrations that also influence the subsequent risk of gout.The ABCG2 Q141 K variant is highly likely to be causal and results in internalization of ABCG2 [7].UP to now, there are at least three urate transporter genes, closely related with occurrence and development of hyperuricaemia: 1) ATP binding transporter G super family (ABCG2), 2) ATP binding transporter G super family, 3) human urate transport protein (HURAT1) [8].The genetic contribution to the progression from hyperuricaemia to CKD remains relatively poorly understood.
But there have been not clearly understood about SNP identifying both URAT1 and CABG2 in hyperuricemia with CKD.So our aim is to identify and analyze Single Nucleotide Polymorphism (SNP) differences of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia in order to identify uncommon genetic variants with increased penetrance that might provide opportunities for clinical translation.Hyperurecimia refers to the normal urine diet under the condition of two fasting uric acid levels.The male is higher than 420 umol/L; the female is higher than 360 umol/L.
3) Biochemistry parameters detection 24 hours urine sample and serum were prepared in both groups patients in for testing biochemistry parameters by Biochemical Analyzer.
Fasting blood samples were (5 ml) extracted in the median cubital vein, DNA is extracted by method of salt bath, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analysis the case group and control group hURAT1, determination of ABCG2 single nucleotide polymorphisms.The identifying method is referred to the literature.The SNP identifying had been finished in Shanghai Genechem Co., Ltd.
Premier were designed as followed:

5) Statistical analysis
All data were statistically processed by SPSS 18.0 software, and the data were represented by x ± s. Variance analysis was conducted.The comparison of the frequencies of genotypes and alleles, genotypes and alleles was conducted by using the direct count method.

Results
Biochemistry parameters in 24 h urinary and serum.
There have differences in24 h urinary protein, creatine and UA between Control and Hyperuricemia group (p < 0.05).But there have no difference in 24 h urinary UA between these groups (p > 0.05).

Discussion
A number of epidemiological reports link hyperuricemia with multiple disorders,  that primarily regulates the renal tubular reabsorption of uric acid.Cho [11] found five newly described SNPs (rs7929627, rs75786299, rs3825017, rs11602903 and rs121907892) in the hURAT1 gene are significantly associated with uric acid level.Sun [12] explored the effect of urate transporter 1 (URAT1) polymorphisms on the hypertensive patients with hyperuricemia and the uricosuric action of losartan therapy among hypertensive patients with hyperuricemia, suggesting that URAT1 rs3825016 and rs1529909 polymorphisms influence the uricosuric action of losartan.Chen et al. [13] in GWAS results showed 36 SNPs to be strongly associated with gout compared to controls (all p-values & lt; 10 (−7)), and ABCG2 gene contributed to hyperuricemia but also gout, and that it was involved in the inflammation dysregulation via augmented IL-8 release in EC.
Up to now, we have known little about SNP identifying both URAT1 and CABG2 in hyperuricemia with CKD.Our work shows that there are higher mutation rate of SNPs of hURAT1 (rs7932775) or ABCG2 (rs3825016) in CKD with hyperuricemia patients compared to controls.We can conclude that hURAT1 (rs7932775) or ABCG2 (rs3825016) may play a part in progress of CKD by triggering oxidative stress, which is necessary to take decrease serum uric acid to delay CKD progress.We also found the higher SNP mutation of
both hURAT1 (rs7932775) and ABCG2 (rs3825016), suggesting the common mechanisms in triggering CKD progress.In the following work, we plan to test SNP of hURAT1 (rs7932775) or ABCG2 (rs3825016) in CKD patients by serum uric acid-lowering drugs Febuxostat and Benzbromarone respectively to explore the common mechanisms from hyperuricemia to CKD progress.SNP mutations patients on followed-up study are more susceptible to cause gout flare and CKD than no-mutation patients, to whom we pay close attention and take intervening measures by giving decreasing serum urice acid medicine.It is worth of further research to explore the exact mechanisms of SNP of URAT1 (rs7932775) and ABCG2 (rs3825016) causing gout and CKD progress.

Table 3 .
Biochemistry parameters in urine and serum between groups.