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Rheumatology International

, Volume 35, Issue 2, pp 337–344 | Cite as

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

  • Angel Soto-Hermida
  • Mercedes Fernández-Moreno
  • Sonia Pértega-Díaz
  • Natividad Oreiro
  • Carlos Fernández-López
  • Francisco J. BlancoEmail author
  • Ignacio Rego-PérezEmail author
Original Article

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.

Keywords

Mitochondria Haplogroups Osteoarthritis Cartilage Progression K/L grade 

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

Notes

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).

Conflict of interest

The authors declare that they have no conflict interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Angel Soto-Hermida
    • 1
  • Mercedes Fernández-Moreno
    • 1
  • Sonia Pértega-Díaz
    • 1
    • 2
  • Natividad Oreiro
    • 1
  • Carlos Fernández-López
    • 1
  • Francisco J. Blanco
    • 1
    • 3
    Email author
  • Ignacio Rego-Pérez
    • 1
    Email author
  1. 1.Grupo de Genómica, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC)Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC)A Coruña, EspañaSpain
  2. 2.Unidad de Epidemiología, Instituto de Investigacion Biomedica de A Coruña (INIBIC)Complexo Hospitalario Universitario de A Coruña (CHUAC), SergasA CoruñaSpain
  3. 3.CIBER de BioingenieriaBiomateriales y Nanomedicina (CIBER-BBN)ValenciaSpain

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