Mitochondrial DNA haplogroups modulate the radiographic progression of Spanish patients with osteoarthritis

Abstract

Not all patients with osteoarthritis (OA) show the same disease progression, as some of them remain relatively stable over time, while others progress to severe structural deterioration of the joint. In this sense, the main goal of both genetic and protein biomarkers in OA is to predict not only the risk of OA at an earlier stage of the disease but also which OA patients are more likely to progress to severe disease. Taking into account the incidence of the mitochondria and the mtDNA haplogroups in the pathogenesis of OA, the main objective of this work was to evaluate the incidence of the mtDNA haplogroups in the radiographic progression of the OA disease in a well-characterized follow-up cohort of Spanish patients. DNA from 281 OA patients from Hospital Universitario A Coruña was isolated to determine the European mtDNA haplogroups. Knee or hip radiographs from all affected joints were obtained at two time points with at least 36 months apart. Radiographs were evaluated using the Kellgren/Lawrence (K/L) scale; radiographic OA progression was defined as any radiographic worsening of the K/L joint score. Statistical analyses included Kaplan–Meier survival curves and Cox regression models. Patients belonging to the cluster TJ showed a slower radiographic OA progression than patients in the cluster KU (p = 0.036). Moreover, patients carrying the most common mtDNA haplogroup H are more apt to require total joint replacement surgery than non-H patients (p = 0.049). The inherited mitochondrial variants influence the radiographic progression of OA and could be considered among the genetic variants taken into account when the radiographic progression of OA is analyzed.

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Abbreviations

ABI:

Applied biosystems

ACR:

American college of Rheumatology

ATP:

Adenosine triphosphate

BMI:

Body mass index

CI:

Confidence interval

CILP:

Cartilage intermediate layer protein

DNA:

Deoxyribonucleic acid

GDF5:

Growth differentiation factor 5

HR:

Hazard ratio

IL1RN:

Interleukin-1 receptor antagonist

JSW:

Joint space width

KL:

Kellgren and Lawrence

MRC:

Mitochondrial respiratory chain

mtDNA:

Mitochondrial deoxyribonucleic acid

OA:

Osteoarthritis

OAI:

Osteoarthritis initiative

OR:

Odds ratio

OXHPOS:

Oxidative phosphorylation system

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

ROS:

Reactive oxygen species

SBE:

Single base extension

SNP:

Single nucleotide polymorphism

SPSS:

Statistical package for the social sciences

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Acknowledgments

The authors express appreciation to Lourdes Sanjurjo and Maria Dolores Velo and to the Department of Orthopaedic Surgery from the CHU A Coruña. This study was supported by grants from Fundación Española de Reumatologia (programa GEN-SER) and from Fondo Investigación Sanitaria (CIBER- CB06/01/0040)-Spain, Fondo Investigacion Sanitaria-PI 12/329 Ministerio Ciencia en Innovacion PLE2009-0144, with participation of funds from FEDER (European Community). Ignacio Rego-perez was supported by Contrato Miguel Servet-Fondo Investigacion Sanitaria (CP12/03192).

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The authors declare that they have no conflict interest.

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Correspondence to Francisco J. Blanco or Ignacio Rego-Pérez.

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Soto-Hermida, A., Fernández-Moreno, M., Pértega-Díaz, S. et al. Mitochondrial DNA haplogroups modulate the radiographic progression of Spanish patients with osteoarthritis. Rheumatol Int 35, 337–344 (2015). https://doi.org/10.1007/s00296-014-3104-1

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Keywords

  • Mitochondria
  • Haplogroups
  • Osteoarthritis
  • Cartilage
  • Progression
  • K/L grade