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Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population

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Harvard

Hagen, CM, Aidt, FH, Hedley, PL, Jensen, MK, Havndrup, O, Kanters, JK, Moolman-Smook, JC, Larsen, SO, Bundgaard, H & Christiansen, M 2013, 'Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population', P L o S One, bind 8, nr. 8, s. e71904. https://doi.org/10.1371/journal.pone.0071904

APA

Hagen, C. M., Aidt, F. H., Hedley, P. L., Jensen, M. K., Havndrup, O., Kanters, J. K., Moolman-Smook, J. C., Larsen, S. O., Bundgaard, H., & Christiansen, M. (2013). Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population. P L o S One, 8(8), e71904. https://doi.org/10.1371/journal.pone.0071904

CBE

MLA

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Author

Hagen, Christian Munch ; Aidt, Frederik Heurlin ; Hedley, Paula L ; Jensen, Morten K. ; Havndrup, Ole ; Kanters, Jørgen K ; Moolman-Smook, Johanna C ; Larsen, Severin O ; Bundgaard, Henning ; Christiansen, Michael. / Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population. I: P L o S One. 2013 ; Bind 8, Nr. 8. s. e71904.

Bibtex

@article{7274695222dc47049efa623394ae1023,
title = "Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population",
abstract = "Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from blood, was sequenced and haplogroups identified in 91 probands with HCM. The association with HCM was ascertained using two Danish control populations. Haplogroup H was more prevalent in HCM patients, 60% versus 46% (p = 0.006) and 41% (p = 0.003), in the two control populations. Haplogroup J was less prevalent, 3% vs. 12.4% (p = 0.017) and 9.1%, (p = 0.06). Likewise, the UK haplogroup cluster was less prevalent in HCM, 11% vs. 22.1% (p = 0.02) and 22.8% (p = 0.04). These results indicate that haplogroup H constitutes a susceptibility factor and that haplogroup J and haplogroup cluster UK are protective factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy suggests that mtDNA haplotypes may be of significance in determining whether a physiological hypertrophy develops into myopathy. mtDNA haplotypes may have the potential of becoming significant biomarkers in cardiomyopathy.",
author = "Hagen, {Christian Munch} and Aidt, {Frederik Heurlin} and Hedley, {Paula L} and Jensen, {Morten K.} and Ole Havndrup and Kanters, {J{\o}rgen K} and Moolman-Smook, {Johanna C} and Larsen, {Severin O} and Henning Bundgaard and Michael Christiansen",
year = "2013",
doi = "10.1371/journal.pone.0071904",
language = "English",
volume = "8",
pages = "e71904",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population

AU - Hagen, Christian Munch

AU - Aidt, Frederik Heurlin

AU - Hedley, Paula L

AU - Jensen, Morten K.

AU - Havndrup, Ole

AU - Kanters, Jørgen K

AU - Moolman-Smook, Johanna C

AU - Larsen, Severin O

AU - Bundgaard, Henning

AU - Christiansen, Michael

PY - 2013

Y1 - 2013

N2 - Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from blood, was sequenced and haplogroups identified in 91 probands with HCM. The association with HCM was ascertained using two Danish control populations. Haplogroup H was more prevalent in HCM patients, 60% versus 46% (p = 0.006) and 41% (p = 0.003), in the two control populations. Haplogroup J was less prevalent, 3% vs. 12.4% (p = 0.017) and 9.1%, (p = 0.06). Likewise, the UK haplogroup cluster was less prevalent in HCM, 11% vs. 22.1% (p = 0.02) and 22.8% (p = 0.04). These results indicate that haplogroup H constitutes a susceptibility factor and that haplogroup J and haplogroup cluster UK are protective factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy suggests that mtDNA haplotypes may be of significance in determining whether a physiological hypertrophy develops into myopathy. mtDNA haplotypes may have the potential of becoming significant biomarkers in cardiomyopathy.

AB - Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from blood, was sequenced and haplogroups identified in 91 probands with HCM. The association with HCM was ascertained using two Danish control populations. Haplogroup H was more prevalent in HCM patients, 60% versus 46% (p = 0.006) and 41% (p = 0.003), in the two control populations. Haplogroup J was less prevalent, 3% vs. 12.4% (p = 0.017) and 9.1%, (p = 0.06). Likewise, the UK haplogroup cluster was less prevalent in HCM, 11% vs. 22.1% (p = 0.02) and 22.8% (p = 0.04). These results indicate that haplogroup H constitutes a susceptibility factor and that haplogroup J and haplogroup cluster UK are protective factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy suggests that mtDNA haplotypes may be of significance in determining whether a physiological hypertrophy develops into myopathy. mtDNA haplotypes may have the potential of becoming significant biomarkers in cardiomyopathy.

U2 - 10.1371/journal.pone.0071904

DO - 10.1371/journal.pone.0071904

M3 - Journal article

C2 - 23940792

VL - 8

SP - e71904

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 8

ER -

ID: 42917474