Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease  

作　　者：Bai Yaling Guo Zhanjun Xu Jinsheng Zhang Junxia Cui Liwen Zhang Huiran Zhang Shenglei Ai Xiaolu 

机构地区：[1]Department of Nephrology,the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China [2]Departments of Gastroenterologyand Hepatology,the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China

出　　处：《Chinese Medical Journal》2014年第17期3088-3091,共4页中华医学杂志（英文版）

摘　　要：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.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.

关 键 词：D-loop peptide chronic kidney disease single nucleotide polymorphism mitochondrial DNA 

分 类 号：R692[医药卫生—泌尿科学]