European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

Aldámiz‐Echevarría, Teresa; Resino, Salvador; Bellón, José María; Jiménez-Sousa, María Ángeles; Miralles, Pilar; Medrano, Luz María; Carrero, Ana; Díez, Cristina; Pérez‐Latorre, Leire; Fanciulli, Chiara; García-Broncano, Pilar; Berenguer, Juan

doi:10.1186/s12967-019-1997-x

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…Hence, we also assigned individuals to one of the major European haplogroups (Fig.4) for comparison. As a result, we observed that 43.28% of the individuals belonged to the macro-haplogroup H, 13.70% to the macro-haplogroup U, 10.70% to the macro-haplogroup J and 9.52% to the macro-haplogroup T (Fig.4), in line with earlier reports in other European populations [2]. Overall, the frequencies of the major European mitochondrial haplogroups did not differ significantly (at FDR<5%) between CAD patients and control subjects (Fig.4).…”

Section: Discussionsupporting

confidence: 91%

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Vilne

Sawant

Rudaka

2022

Preprint

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Background: Large-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain <20% of the heritability. Hypothesis: Here, we hypothesize that mitochondrial (MT) SNVs might present one potential source of this "missing heritability". Methods: We analyzed 265 MT-SNVs in ~500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularisation; HARD=20,405), and a more inclusive (also angina and chronic ischemic heart disease; SOFT=34,782). Results: In HARD cases, the most significant (P<0.05) associations were for m.295C>T (control region) and m.12612A>G (ND5), found more frequently in cases (OR=1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR=0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing correction (at FDR<5%), all potentially conferring increased CAD risk. Of those, m.11251A>G (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active and their average body height was ~2.00 cm lower compared to controls, both traits known to be related to an increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (P<0.05), dysfunction of which has been related to MT oxidative stress, obesity/T2D (CO2), BMI (ND3) and angina/exercise intolerance (CYB). Finally, we observed that macro-haplogroup I was significantly (P<0.05) more frequent in HARD cases vs. controls (3.35% vs. 3.08%), potentially associated with response to exercise. Conclusions: We found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT- SNV data in even larger study cohorts may be needed to conclusively determine the role of MT-DNA in CAD.

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Section: Discussionsupporting

confidence: 91%

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Vilne

Sawant

Rudaka

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Hence, we also assigned individuals to one of the major European haplogroups ( Figure 4 ) for comparison. As a result, we observed that 43.28% of the individuals belonged to the macro-haplogroup H, 13.70% to the macro-haplogroup U, 10.70% to the macro-haplogroup J, and 9.52% to the macro-haplogroup T ( Figure 4 ), in line with previous reports in other European populations [ 71 ]. Overall, the frequencies of the major European mitochondrial haplogroups did not differ significantly (at FDR < 5%) between CAD patients and control subjects ( Figure 4 ).…”

Section: Discussionsupporting

confidence: 90%

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Vilne

Sawant

Rudaka

2022

Genes

View full text Add to dashboard Cite

Large-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain <20% of the heritability. Hypothesis: Here, we hypothesize that mitochondrial (MT)-SNVs might present one potential source of this “missing heritability”. Methods: We analyzed 265 MT-SNVs in ~500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularization; HARD = 20,405), and a more inclusive (angina and chronic ischemic heart disease; SOFT = 34,782). Results: In HARD cases, the most significant (p < 0.05) associations were for m.295C>T (control region) and m.12612A>G (ND5), found more frequently in cases (OR = 1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR = 0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing corrections (at FDR < 5%), all potentially conferring increased CAD risk. Of those, m.11251A>G (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active, and their average body height was ~2.00 cm lower compared to controls; both traits are known to be related to increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (p < 0.05), dysfunction of which has been related to MT oxidative stress, obesity/T2D (CO2), BMI (ND3), and angina/exercise intolerance (CYB). Finally, we observed that macro-haplogroup I was significantly (p < 0.05) more frequent in HARD cases vs. controls (3.35% vs. 3.08%), potentially associated with response to exercise. Conclusions: We found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT-SNV data in even larger study cohorts may be needed to conclusively determine the role of MT DNA in CAD.

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“…Global DNA methylation was evaluated by a MethylFlashTM Methylated DNA Quanti cation Kit (Epigentek, NY, USA) according to the instructions and bisul te DNA sequencing was carried by Sequenom MassARRAY platform (BGI.write, Beijing, China) as previously reported [19].…”

Section: Global Dna Methylation Assay and Bisul Te Dna Sequencingmentioning

confidence: 99%

MBD2 facilitates tumor metastasis by mitigating DDB2 expression

Zhang

Wang

Wu³

et al. 2022

Preprint

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Despite past extensive studies, the pathoetiologies underlying tumor metastasis remain poorly understood, which renders its treatment largely unsuccessful. The methyl-CpG-binding domain 2 (MBD2), a “reader” to interpret DNA methylome-encoded information, has been noted to be involved in the development of certain types of tumors, while its exact impact on tumor metastasis remains elusive. Herein we demonstrated that patients with LUAD metastasis were highly correlated with enhanced MBD2 expression. Therefore, knockdown of MBD2 significantly attenuated the migration and invasion of LUAD cells (A549 and H1975 cell lines) coupled with attenuated epithelial–mesenchymal transition (EMT). Moreover, similar results were observed in other types of tumor cells (B16F10). Mechanistically, MBD2 selectively bound to the methylated CpG DNA within the DDB2 promoter, by which MBD2 repressed DDB2 expression to promote tumor metastasis. As a result, administration of MBD2 siRNA-loaded liposomes remarkably suppressed EMT along with attenuated tumor metastasis in the B16F10 tumor-bearing mice. Collectively, our study indicates that MBD2 could be a promising prognostic marker for tumor metastasis, while administration of MBD2 siRNA-loaded liposomes could be a viable therapeutic approach against tumor metastasis in clinical settings.

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European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

Cited by 6 publications

References 45 publications

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

MBD2 facilitates tumor metastasis by mitigating DDB2 expression

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