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 diseas...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 necessary to take measures of decreasing serum uric acid to delay CKD progress.展开更多
Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Hypertensive nephrosclerosis is a subtype of CKD whi...Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Hypertensive nephrosclerosis is a subtype of CKD which has a poor correlation between hypertension and development of nephropathy, implying role of genetic factors or epigenetic factors. The knowledge regarding genetic factors is limited. Renalase is a novel hormone with its gene on chromosome 10, which secretes flavin adenine dinucleotide dependent amine oxidase. Renalase metabolizes circulating catecholamines and modulates blood pressure and cardiac function. Recently, two single nucleotide polymorphisms of renalase gene rs2576178 GG and rs2296545 CC have been linked to essential hypertension. The SNPrs2296545 CC is also shown to be associated with cardiac hypertrophy, dysfunction and ischemia. The association of these two single nucleotide polymorphisms with hypertensive nephrosclerosis has not been investigated. Methods: We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD particularly hypertensive nephrosclerosis. We genotyped these two polymorphisms in 287 subjects from North Indian population (106 CKD cases and 181 controls). Results: Comparison shows that subjects with hypertensive nephrosclerosis had higher frequencies of rs2296545 Callele than the healthy controls (0.63 versus 0.47, p 0.02). The odds ratio for rs2296545 CC genotype in hypertensive nephrosclerosis were 2.55 (95% CI, 1.03 to 6.42;p = 0.02) (CC versus GG) and 2.11(95% CI, 1.01 to 4.42;p = 0.03) (CC versus CG + GG) compared to controls. Conclusion: These findings may provide novel insight into the role of additional genomic regions as susceptibility gene in the pathophysiology of hypertensive nephrosclerosis. Further, to account for geoethnic variation, studies on heterogeneous populations involving a larger sample size are required. The correlation between this structural change and actual levels of the enzyme or the activity are required to strengthen this association as well as to be clinically applicable.展开更多
Background The mitochondrial displacement loop （D-loop） accumulates mutations and single nucleotide polymorphisms （SNPs） at a higher frequency than other regions of mitochondrial DNA （mtDNA）.We previously identi...Background The mitochondrial displacement loop （D-loop） accumulates mutations and single nucleotide polymorphisms （SNPs） at a higher frequency than other regions of mitochondrial DNA （mtDNA）.We previously identified disease riskassociated SNPs in the D-loop of chronic kidney disease （CKD） patients; in this study,we investigated the association of age-at-onset and D-loop SNPs in CKD patients.Methods The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008.The age-at-onset curve of the CKD patients was calculated using the KaplanMeier method at each SNP site,and compared using the log-rank test.Results The mean age of 119 CKD patients was （55.6±14.2） years,and 56.3% were males.The mean estimated glomerular filtration rate （eGFR） was （81.2±12.4） ml·min^-1·1.73 m^-2,with 79.8% （n=95） of patients having an eGFR 〈60 ml·min^-1·1.73 m^-2.All participants had an eGFR 〉30 ml·min^-1·1.73 m^-2.The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients.The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test.The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site （P=0.010）.Conclusions Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients.Accordingly,the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.展开更多
文摘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 necessary to take measures of decreasing serum uric acid to delay CKD progress.
文摘Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Hypertensive nephrosclerosis is a subtype of CKD which has a poor correlation between hypertension and development of nephropathy, implying role of genetic factors or epigenetic factors. The knowledge regarding genetic factors is limited. Renalase is a novel hormone with its gene on chromosome 10, which secretes flavin adenine dinucleotide dependent amine oxidase. Renalase metabolizes circulating catecholamines and modulates blood pressure and cardiac function. Recently, two single nucleotide polymorphisms of renalase gene rs2576178 GG and rs2296545 CC have been linked to essential hypertension. The SNPrs2296545 CC is also shown to be associated with cardiac hypertrophy, dysfunction and ischemia. The association of these two single nucleotide polymorphisms with hypertensive nephrosclerosis has not been investigated. Methods: We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD particularly hypertensive nephrosclerosis. We genotyped these two polymorphisms in 287 subjects from North Indian population (106 CKD cases and 181 controls). Results: Comparison shows that subjects with hypertensive nephrosclerosis had higher frequencies of rs2296545 Callele than the healthy controls (0.63 versus 0.47, p 0.02). The odds ratio for rs2296545 CC genotype in hypertensive nephrosclerosis were 2.55 (95% CI, 1.03 to 6.42;p = 0.02) (CC versus GG) and 2.11(95% CI, 1.01 to 4.42;p = 0.03) (CC versus CG + GG) compared to controls. Conclusion: These findings may provide novel insight into the role of additional genomic regions as susceptibility gene in the pathophysiology of hypertensive nephrosclerosis. Further, to account for geoethnic variation, studies on heterogeneous populations involving a larger sample size are required. The correlation between this structural change and actual levels of the enzyme or the activity are required to strengthen this association as well as to be clinically applicable.
文摘Background The mitochondrial displacement loop （D-loop） accumulates mutations and single nucleotide polymorphisms （SNPs） at a higher frequency than other regions of mitochondrial DNA （mtDNA）.We previously identified disease riskassociated SNPs in the D-loop of chronic kidney disease （CKD） patients; in this study,we investigated the association of age-at-onset and D-loop SNPs in CKD patients.Methods The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008.The age-at-onset curve of the CKD patients was calculated using the KaplanMeier method at each SNP site,and compared using the log-rank test.Results The mean age of 119 CKD patients was （55.6±14.2） years,and 56.3% were males.The mean estimated glomerular filtration rate （eGFR） was （81.2±12.4） ml·min^-1·1.73 m^-2,with 79.8% （n=95） of patients having an eGFR 〈60 ml·min^-1·1.73 m^-2.All participants had an eGFR 〉30 ml·min^-1·1.73 m^-2.The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients.The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test.The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site （P=0.010）.Conclusions Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients.Accordingly,the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.
