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.
