Yaling Bai1, Zhanjun Guo2, Jinsheng Xu3, Junxia Zhang1, Liwen Cui1, Huiran Zhang1, Shenglei Zhang1, Xiaolu Ai1. 1. Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China. 2. Departments of Gastroenterology and Hepatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China. 3. Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China. Email: xjs5766@126.com.
Abstract
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 risk-associated 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 Kaplan-Meier 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 risk-associated 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 CKDpatients. METHODS: The D-loop region of mtDNA was sequenced in 119 CKDpatients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008. The age-at-onset curve of the CKDpatients was calculated using the Kaplan-Meier method at each SNP site, and compared using the log-rank test. RESULTS: The mean age of 119 CKDpatients 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 CKDpatients who smoked was significantly lower than that of non-smoking CKDpatients. 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 CKDpatients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKDpatient subgroups at high risk of early onset disease.