TY - JOUR

T1 - Evolutionary dissection of mtDNA hg H

T2 - a susceptibility factor for hypertrophic cardiomyopathy

AU - Hagen, Christian M.

AU - Elson, Joanna L.

AU - Hedley, Paula L.

AU - Aidt, Frederik H.

AU - Havndrup, Ole

AU - Jensen, Morten K.

AU - Kanters, Jørgen K.

AU - Atherton, John J.

AU - McGaughran, Julie

AU - Bundgaard, Henning

AU - Christiansen, Michael

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Haplogroup and MutPred

KW - Hypertrophic cardiomyopathy

KW - mtDNA

U2 - 10.1080/24701394.2020.1782897

DO - 10.1080/24701394.2020.1782897

M3 - Journal article

C2 - 32602800

AN - SCOPUS:85087573712

VL - 31

SP - 238

EP - 244

JO - Mitochondrial DNA Part A: DNA Mapping, Sequencing, and Analysis

JF - Mitochondrial DNA Part A: DNA Mapping, Sequencing, and Analysis

SN - 2470-1394

IS - 6

ER -