Associations of mitochondrial haplogroups and mitochondrial DNA copy numbers with end-stage renal disease in a Han population

Abstract

Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations have been suggested to be involved in pathogenesis of complex diseases. The present study sought to elucidate mitochondrial haplogroups and mtDNA copy number in end-stage renal disease (ESRD) in a Han population. First, the mitochondrial haplogroups of 37 ESRD patients were clustered into several haplogroups, and haplogroup A & D were taken as the candidate risk haplogroups for ESRD. Second, the frequencies of A and D were assessed in 344 ESRD patients and 438 healthy controls, respectively. Haplogroup D was found to be risk maker for ESRD in young subjects (<30 years) with an OR of 2.274. Finally, intracellular and cell-free mtDNA copy numbers were evaluated with quantitative-PCR. The ESRD patients exhibited greater cell-free mtDNA contents than the healthy controls but less intracellular mtDNA. Haplogroup D exhibited a further increase in cell-free mtDNA content and a decrease in intracellular mtDNA content among the ESRDs patients. Our findings suggest that mtNDA haplogroup D may contributes to pathogenesis of early-onset ESRD through alterations of mtDNA copy numbers.

Keywords:

• Copy number
• end-stage renal disease
• haplogroup
• Mitochondrial DNA

Acknowledgments

The authors would like to thank Professor Wang Yaping at the Jiangsu Key Laboratory of Molecular Medicine for the laboratory equipment and general materials. The authors thank native speaker Biji Mathilakath for the linguistic review.

Disclosure statement

The authors report that they have no conflict of interests. This work was supported by the National Natural Science Foundation of China under Grant 81370788 & 8151101098; 'Six Major Talent Peaks' of Jiangsu Province, China under Grant WSN-071-2012. The authors alone are responsible for the content and writing of the paper.