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

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 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 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.