Evolutionary dissection of mtDNA hg H: a susceptibility factor for hypertrophic cardiomyopathy

Abstract

Mitochondrial DNA (mtDNA) haplogroup (hg) H has been reported as a susceptibility factor for hypertrophic cardiomyopathy (HCM). This was established in genetic association studies, however, the SNP or SNP’s that are associated with the increased risk have not been identified. Hg H is the most frequent European mtDNA hg with greater than 80 subhaplogroups (subhgs) each defined by specific SNPs. We tested the hypothesis that the distribution of H subhgs might differ between HCM patients and controls. The subhg H distribution in 55 HCM index cases was compared to that of two Danish mtDNA hg H control groups (n = 170 and n = 908, respectively). In the HCM group, H and 12 different H subhgs were found. All these, except subhgs H73, were also found in both control groups. The HCM group was also characterized by a higher proportion of H3 compared to H2. In the HCM group the H3/H2 proportion was 1.7, whereas it was 0.45 and 0.54 in the control groups. This tendency was replicated in an independent group of Hg H HCM index cases (n = 39) from Queensland, Australia, where the H3/H2 ratio was 1.5. In conclusion, the H subhgs distribution differs between HCM cases and controls, but the difference is subtle, and the understanding of the pathogenic significance is hampered by the lack of functional studies on the subhgs of H.

Keywords:

• Hypertrophic cardiomyopathy
• mtDNA
• Haplogroup and MutPred

Acknowledgements

This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation. The technical assistance of Dennis Jelsbak Schmidt is acknowledged.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors gratefully acknowledge the financial support of The Strategic Research Council (“Heart Safe”), The Augustinus Foundation, The Lundbeck Foundation [Grant no. R67-A6552], and Familien Hede Nielsens Fond. The iPSYCH study was funded by The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) - The Lundbeck Foundation [LF Grant number: R102-A9118].