J Rheum Dis.  2020 Jul;27(3):168-173. 10.4078/jrd.2020.27.3.168.

Analysis of Asian Mitochondrial DNA Haplogroups Associated With the Progression of Knee Osteoarthritis in Koreans

• Koo BS
• Song Y
• Lee S
• Sung YK
• Shin KJ
• Cho NH
• Jun JB

• KMID: 2504032
• DOI: http://doi.org/10.4078/jrd.2020.27.3.168

Abstract

Objective
. We investigated Asian mitochondrial DNA (mtDNA) haplogroups associated with knee osteoarthritis (OA) progression in a prospective community-based cohort comprised of Koreans.
Methods
. Epidemiologic data and Kellgren-Lawrence (K/L) scores of knee radiographs were obtained from the second (2005∼2006) and sixth (2013∼2014) follow-up, and patient DNA was analyzed. The mtDNA haplogroup frequencies (M, G, D, D4, D5, M7, M8, M9, M10, N, A, N9, R, F, and B) were compared between the progression (K/L score change on either knee ≥2 or arthroplasty) and non-progression (K/L score change on both knee ≤1) groups at the sixth follow-up. Multiple logistic regression was performed to determine relative risk (RRs) of mtDNA haplogroups for OA.
Results
. In total, 1,115 participants were included, 405 of whom had early OA (higher K/L score on both knees of 1 or 2). Among them, 143 and 166 patients were classified in non-progression and progression groups, respectively, at the sixth follow-up. The most frequent haplogroups, B and D4, in Koreans also showed a high frequency in our study. There were no significantly different haplogroups between the non-progression and progression groups. However, the frequency of haplogroup D4 was likely higher in the non-progression group than in the progression group, although not significantly (13.3% vs. 7.2%, RR=0.51, p=0.081 in the unadjusted model and RR=0.56, p=0.149 in the adjusted model).
Conclusion
. No significant haplogroups are related to OA progression. Large-scaled studies are needed to reveal the association between mtDNA haplogroups and OA.

Keyword

Korea; Mitochondrial DNA; Osteoarthritis of the knee

Figure

• 

  Figure 1 Classification according to the Kellgren-Lawrence (K/L) score at each follow-up in the study cohort. The frequencies of mitochondrial DNA haplogroups were analyzed in the non-progression and progression groups (box surrounded by the dotted line).

Reference

1. Blanco FJ, Valdes AM, Rego-Pérez I. 2018; Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes. Nat Rev Rheumatol. 14:327–40. DOI: 10.1038/s41584-018-0001-0. PMID: 29670212.

2. Koo BS, Song Y, Lee S, Sung YK, Shin KJ, Cho NH, et al. 2019; Association of Asian mitochondrial DNA haplogroup B with new development of knee osteoarthritis in Koreans. Int J Rheum Dis. 22:411–6. DOI: 10.1111/1756-185X.13453. PMID: 30549233.

3. Blanco FJ, Rego I, Ruiz-Romero C. 2011; The role of mitochondria in osteoarthritis. Nat Rev Rheumatol. 7:161–9. DOI: 10.1038/nrrheum.2010.213. PMID: 21200395.

4. Fernández-Moreno M, Soto-Hermida A, Vázquez-Mosquera ME, Cortés-Pereira E, Relaño S, Hermida-Gómez T, et al. 2017; Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts. A meta-analysis and functional study. Ann Rheum Dis. 76:1114–22. DOI: 10.1136/annrheumdis-2016-210131. PMID: 27919866.

5. Lotz M, Martel-Pelletier J, Christiansen C, Brandi ML, Bruyère O, Chapurlat R, et al. 2013; Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis. 72:1756–63. DOI: 10.1136/annrheumdis-2013-203726. PMID: 23897772. PMCID: PMC3812859.

6. Minafra L, Bravatà V, Saporito M, Cammarata FP, Forte GI, Caldarella S, et al. 2014; Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility. Arthritis Res Ther. 16:R91. DOI: 10.1186/ar4535. PMID: 24716474. PMCID: PMC4060235.

7. Rego I, Fernández-Moreno M, Fernández-López C, Gómez-Reino JJ, González A, Arenas J, et al. 2010; Role of European mitochondrial DNA haplogroups in the prevalence of hip osteoarthritis in Galicia, Northern Spain. Ann Rheum Dis. 69:210–3. DOI: 10.1136/ard.2008.105254. PMID: 19224903.

8. Rego-Pérez I, Fernández-Moreno M, Fernández-López C, Arenas J, Blanco FJ. 2008; Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis. Arthritis Rheum. 58:2387–96. DOI: 10.1002/art.23659. PMID: 18668590.

9. Fernández-Moreno M, Soto-Hermida A, Vázquez-Mosquera ME, Cortés-Pereira E, Pértega S, Relaño S, et al. 2017; A replication study and meta-analysis of mitochondrial DNA variants in the radiographic progression of knee osteoarthritis. Rheumatology (Oxford). 56:263–70. DOI: 10.1093/rheumatology/kew394. PMID: 27864563. PMCID: PMC5854036.

10. Soto-Hermida A, Fernández-Moreno M, Oreiro N, Fernández-López C, Pértega S, Cortés-Pereira E, et al. 2014; Mitochondrial DNA (mtDNA) haplogroups influence the progression of knee osteoarthritis. Data from the Osteoarthritis Initiative (OAI). PLoS One. 9:e112735. DOI: 10.1371/journal.pone.0112735. PMID: 25390621. PMCID: PMC4229258.

11. Soto-Hermida A, Fernández-Moreno M, Pértega-Díaz S, Oreiro N, Fernández-López C, Blanco FJ, et al. 2015; Mitochondrial DNA haplogroups modulate the radiographic progression of Spanish patients with osteoarthritis. Rheumatol Int. 35:337–44. DOI: 10.1007/s00296-014-3104-1. PMID: 25086630.

12. Cho NH, Kim JY, Kim SS, Shin C. 2013; The relationship of metabolic syndrome and constitutional medicine for the prediction of cardiovascular disease. Diabetes Metab Syndr. 7:226–32. DOI: 10.1016/j.dsx.2013.08.003. PMID: 24290090.

13. Cho NH, Song Y, Lee S, Sung YK, Jun JB. 2018; Incidence of knee chondrocalcinosis and its risk factors in a community-based cohort. Int J Rheum Dis. 21:1391–7. DOI: 10.1111/1756-185X.13317. PMID: 29968327.

14. Lee HY, Yoon JA, Yang WI, Shin KJ. 2013; A one step multiplex PCR assay for rapid screening of East Asian mtDNA haplogroups on forensic samples. Leg Med (Tokyo). 15:50–4. DOI: 10.1016/j.legalmed.2012.08.002. PMID: 22981178.

15. Allen KD, Golightly YM. 2015; State of the evidence. Curr Opin Rheumatol. 27:276–83. DOI: 10.1097/BOR.0000000000000161. PMID: 25775186. PMCID: PMC4405030.

16. Fang H, Zhang F, Li F, Shi H, Ma L, Du M, et al. 2016; Mitochondrial DNA haplogroups modify the risk of osteoarthritis by altering mitochondrial function and intracellular mitochondrial signals. Biochim Biophys Acta. 1862:829–36. DOI: 10.1016/j.bbadis.2015.12.017. PMID: 26705675.

17. Park S, Cho S, Seo HJ, Lee JH, Kim MY, Lee SD. 2017; Entire mitochondrial DNA sequencing on massively parallel sequencing for the Korean population. J Korean Med Sci. 32:587–92. DOI: 10.3346/jkms.2017.32.4.587. PMID: 28244283. PMCID: PMC5334155.

18. Liou CW, Chen JB, Tiao MM, Weng SW, Huang TL, Chuang JH, et al. 2012; Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes. Diabetes. 61:2642–51. DOI: 10.2337/db11-1369. PMID: 22891220. PMCID: PMC3447893.

19. Jiang W, Li R, Zhang Y, Wang P, Wu T, Lin J, et al. 2017; Mitochondrial DNA mutations associated with type 2 diabetes mellitus in Chinese uyghur population. Sci Rep. 7:16989. DOI: 10.1038/s41598-017-17086-7. PMID: 29208909. PMCID: PMC5717000.

20. Fuku N, Park KS, Yamada Y, Nishigaki Y, Cho YM, Matsuo H, et al. 2007; Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. Am J Hum Genet. 80:407–15. DOI: 10.1086/512202. PMID: 17273962. PMCID: PMC1821119.

21. Williams MF, London DA, Husni EM, Navaneethan S, Kashyap SR. 2016; Type 2 diabetes and osteoarthritis: a systematic review and meta-analysis. J Diabetes Complications. 30:944–50. DOI: 10.1016/j.jdiacomp.2016.02.016. PMID: 27114387.