Research Article: Mitochondrial genetic haplogroups and cardiovascular diseases: Data from the Osteoarthritis Initiative

Date Published: March 28, 2019

Publisher: Public Library of Science

Author(s): Nicola Veronese, Brendon Stubbs, Ai Koyanagi, Alberto Vaona, Jacopo Demurtas, Patricia Schofield, Stefania Maggi, Viorel Simion.


Some case-control studies reported that mitochondrial haplogroups could be associated with the onset of cardiovascular diseases (CVD), but the literature regarding this topic is limited. We aimed to investigate whether any mitochondrial haplogroup carried a higher or lower risk of CVD in a large cohort of North American people affected by knee osteoarthritis or at high risk for this condition.

A longitudinal cohort study including individuals from the Osteoarthritis Initiative was done. Haplogroups were assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups have been named following this nomenclature: HV, JT, UK, IWX, and superHV/others. The strength of the association between mitochondrial haplogroups and incident CVD was evaluated through a Cox’s regression analysis, adjusted for potential confounders, and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs).

Overall, 3,288 Caucasian participants (56.8% women) with a mean age of 61.3±9.2 years without CVD at baseline were included. During a median follow-up of 8 years, 322 individuals (= 9.8% of baseline population) developed a CVD. After adjusting for 11 potential confounders at baseline and taking those with the HV haplotype as reference (the most frequent), those with JT carried a significant lower risk of CVD (HR = 0.75; 95%CI: 0.54–0.96; p = 0.03). Participants with the J haplogroup had the lowest risk of CVD (HR = 0.71; 95%CI: 0.46–0.95; p = 0.02).

The presence of JT haplogroups (particularly J) may be associated with a reduced risk of CVD. However, this result was not based on a high level of statistical significance. Thus, future research with larger sample size is needed to assess whether our results can be corroborated.

Partial Text

The human mitochondrial genome is a circular set of 16,569 base pairs encoding 37 genes, which are translated into 13 proteins involved in the electron transfer chain, a process essential for cellular function and survival [1]. Mitochondrial DNA (mtDNA) often undergoes mutations, though at a much higher rate than nuclear DNA replication rate, while DNA repair mechanisms are less efficient [1, 2]. In addition, the evolution of mtDNA occurs at a more rapid pace compared to the average nuclear DNA, and thus mutations have accumulated sequentially along radiating maternal lineages [3]. Mismatch can lead to single nucleotide polymorphisms (SNPs), and clusters of these specific SNPs in the mitochondrial genome define mitochondrial haplogroups. Not only germline mutations of the nuclear DNA can be on the basis of the genetic susceptibility to different diseases including cancer [4, 5], but also the biology of mtDNA may explain in part the genetic predisposition to certain pathological processes: mutations in mtDNA, in fact, may influence propensity of subjects to several medical conditions [6–8]. Moreover, inherited mutations of mtDNA lead to several diseases in children that mainly affect central nervous system, muscles and the heart [9].

In this paper, in a cohort of people having knee OA or at high risk for this condition, over a follow-up period of 8 years, we found that people who had an JT haplogroup carried a significantly lower risk of CVD of 25%, compared to the most frequent haplotypes (HV). This finding remained significant after multivariable adjustment for several potential confounders assessed at baseline.




Leave a Reply

Your email address will not be published.