The Mitochondrial DNA (mtDNA) Haplogroups Influence the Risk of Incidence Knee OA. Replication Study Including Data from Check and OAI Cohorts

Ignacio Rego-Pérez¹, Angel Soto-Hermida¹, Juan Fernandez-Tajes¹, Mercedes Fernandez Moreno¹, Maria Eugenia Vazquez Mosquera¹, Estefanía Cortés-Pereira¹, Sonia Pertega², Sara Relaño-Fernandez¹, Natividad Oreiro¹, Carlos Fernandez-Lopez¹ and Francisco J. Blanco¹, ¹Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, ²Unidad de Epidemiología Clínica y Bioestadística. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Genetic Biomarkers, Mitochondria, osteoarthritis and radiography

Session Information

Date: Sunday, November 8, 2015

Title: Genetics, Genomics and Proteomics Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Previous studies showed a significant influence of the mtDNA haplogroups on prevalence, radiographic progression and cartilage integrity of knee OA patients from different worldwide cohorts. The aim of this study is to analyze the influence of the mitochondrial variants on the risk of incident knee OA in patients from CHECK as well as in an updated cohort of OAI patients.

Methods:

We assessed the mtDNA haplogroups in 1003 DNA samples from CHECK and 3681 Caucasian samples from the OAI. Incident knee OA was defined as a KL score <2 at baseline and a KL≥2 during 8 (CHECK) and 4 (OAI) years follow-up. Patients suitable for incident knee OA study (KL≤1 at baseline) consisted in 768 and 2409 respectively. Statistical analyses included chi-square contingency tables and logistic regression models considering age, gender, body mass index (BMI), bilateral KL=1 (CHECK) or contralateral knee OA (OAI) at baseline and mtDNA variants as variables of interest.

Results:

After 8 and 4 years respectively, patients from CHECK had more radiographic change compared with the OAI group (p<0,001) so that 418 (54,4%) patients from CHECK and 326 (13,5%) patients from OAI underwent incident knee OA. Patients carrying the haplogroups of the mitochondrial cluster TJ were significantly underrepresented in the incident knee OA group of both cohorts when compared with the most common mtDNA haplogroup H/HV (OR=0,598; CI=0,357-0,999; p=0.05 for the CHECK cohort and OR=0,658; CI=0,467-0,927; p=0.017 for the OAI cohort). In addition, bilateral KL=1 at baseline in the CHECK cohort and contralateral knee OA in the OAI cohort were risk factors to develop incident knee OA (p<0,001). For both cohorts BMI was a risk factor too (p=0,023 and p<0,001 respectively) (Tables 1 and 2). The AUC of the regression models ranged from 0,643 to 0,688.

Conclusion:

The mitochondrial genome contributes to the development of incident knee OA in two well-defined follow-up cohorts, one of them an early-stage OA cohort (CHECK). The assignment of the mitochondrial polymorphisms common to the major mtDNA clusters could be used as complementary genetic biomarkers to predict the risk of incident knee OA.

Table 1. Percentage of OA patients from the CHECK cohort that underwent incident knee OA during 8 years follow-up according to mtDNA haplogroups and results of the regression model

Variables	N (% Incidents)	OR	95% CI	p-value
Gender (female)		1,204	0,823-1,759	0,339
Age		1,025	0,995-1,056	0,107
BMI		1,047	1,006-1,089	0,023*
Bilateral KL=1 at baseline		4,943	3,347-7,301	<0,001*
mtDNA haplogroups
H (n=320)	181 (56,6%)	1	–	–
Uk (n=176)	97 (55.1%)	0,963	0,647-1,434	0,855
J (n=65)	35 (53,8%)	0,966	0,541-1,724	0,906
T (n=87)	39 (44,8%)	0,598	0,357-0,999	0,050*
Others (n=120)	66 (55,0%)	0,939	0,595-1,481	0,787
KL: Kellgren and Lawrence; mtDNA: mitochondrial DNA; OR: odd ratio; CI: confidence interval; BMI: body mass index; (*): statistical significance declared at p≤0.05 (the most common mtDNA haplogroup H was used as reference group)

Table 2. Percentage of OA patients from the OAI cohort that underwent incident knee OA during 4 years follow-up according to mtDNA clusters and results of the regression model

Variables	N (% Incidents)	OR	95% CI	p-value
Gender (female)		1,540	1,205-1,968	0,001*
Age		1,003	0,990-1,016	0,682
BMI		1,068	1,040-1,096	<0,001*
Contralateral (KL≥2) OA at baseline		1,830	1,434-2,336	<0,001*
mtDNA clusters
HV (n=1123)	168 (15,0%)	1	–	–
KU (n=565)	78 (13,8%)	0,920	0,684-1,237	0,581
TJ (n=471)	50 (10,6%)	0,658	0,467-0,927	0,017*
Others (n=250)	30 (12,0%)	0,793	0,518-1,215	0,287
KL: Kellgren and Lawrence; mtDNA: mitochondrial DNA; OR: odd ratio; CI: confidence interval; BMI: body mass index; (*): statistical significance declared at p≤0.05 (the most common mtDNA cluster HV was used as reference group)

Disclosure: I. Rego-Pérez, None; A. Soto-Hermida, None; J. Fernandez-Tajes, None; M. Fernandez Moreno, None; M. E. Vazquez Mosquera, None; E. Cortés-Pereira, None; S. Pertega, None; S. Relaño-Fernandez, None; N. Oreiro, None; C. Fernandez-Lopez, None; F. J. Blanco, Pfizer, Bioiberica, and Gebro Pharma, 5.

To cite this abstract in AMA style:

Rego-Pérez I, Soto-Hermida A, Fernandez-Tajes J, Fernandez Moreno M, Vazquez Mosquera ME, Cortés-Pereira E, Pertega S, Relaño-Fernandez S, Oreiro N, Fernandez-Lopez C, Blanco FJ. The Mitochondrial DNA (mtDNA) Haplogroups Influence the Risk of Incidence Knee OA. Replication Study Including Data from Check and OAI Cohorts [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-mitochondrial-dna-mtdna-haplogroups-influence-the-risk-of-incidence-knee-oa-replication-study-including-data-from-check-and-oai-cohorts/. Accessed .

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