Mitofusin 2 polymorphic variants and left ventricular hypertrophy in human hypertension

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Essential hypertension (n=345). Intervention: MFN2/rs2336384 G allele vs. Non-carriers (TT or TG genotypes). Primary outcome: Risk of left ventricular hypertrophy (LVH) (OR 2.162, 95% CI 1.32-3.64, p=0.0042).

Q: What does this research mean for the field?

Carrier status of the G allele at MFN2/rs2336384 is significantly associated with an increased risk of left ventricular hypertrophy in hypertensive patients. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Giovanna Gallo; Giuliano Tocci; Giulia Nardoianni; Maria Cotugno; Donatella Pietrangelo; Margherita Litterio; Caroline Lopa; Allegra Battistoni; Camillo Autore; Massimo Volpe; Emanuele Barbato

doi:10.1038/s41371-026-01208-8

August 20, 2026Journal of Human Hypertension

Mitofusin 2 polymorphic variants and left ventricular hypertrophy in human hypertension

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Key result

Carrier status of the G allele at MFN2/rs2336384 was significantly associated with an increased risk of left ventricular hypertrophy in hypertensive patients (OR 2.162).

Why the study?

Previous experimental studies showed that dysfunctions of mitofusin 2 are associated with left ventricular hypertrophy, but the association of MFN2 polymorphic variants with LVH in human hypertension was not established.

Does the carrier status of MFN2 polymorphic variants (rs2336384 and rs2236057) increase the risk of left ventricular hypertrophy in hypertensive patients?

Key Points

To assess whether polymorphic variants in the mitofusin 2 (MFN2) gene are associated with left ventricular hypertrophy (LVH) in individuals with hypertension.
Evaluated 345 hypertensive patients (mean age 60 ± 14 years; 199 male, 57.6%) using echocardiography to identify LVH based on 2024 ESC Guidelines.
Genotyped two MFN2 single nucleotide polymorphisms (rs2336384 and rs2236057) to evaluate genotype and allele frequency distributions.
Conducted covariate ANOVA and multivariable logistic regression adjusted for age, gender, BMI, office and 24-hour blood pressure, and antihypertensive medications.
Left ventricular hypertrophy was present in 113 of 345 hypertensive patients (32.7%).
Carrying the G allele at MFN2 rs2336384 was significantly associated with an increased risk of LVH (OR = 2.162; 95% CI, 1.32–3.64; p = 0.0042).
Carrying the A allele at MFN2 rs2236057 was also independently associated with increased odds of LVH (OR = 1.594; 95% CI, 1.12–2.28; p = 0.0093).

Study Design

Type

Cross-Sectional (n=345)

Multicenter

No

Structured PICO

Does the carrier status of MFN2 polymorphic variants (rs2336384 and rs2236057) increase the risk of left ventricular hypertrophy in hypertensive patients?

P

Population

345 Caucasian adults with essential hypertension, free from other clinical conditions potentially causing left ventricular hypertrophy, were evaluated for the association of MFN2 polymorphic variants with left ventricular hypertrophy.

E

Exposure

Carrier status of MFN2 polymorphic variants: G allele at rs2336384 (GG genotype) and A allele at rs2236057 (AA genotype)

C

Comparator

Wild-type and heterozygous genotypes: TT or TG genotypes for rs2336384, and GG or GA genotypes for rs2236057

O

Outcome

Presence of left ventricular hypertrophy (LVH) defined by echocardiography (LV mass/height2.7 >50 g/m2.7 in men and >47 in women, or LV mass/BSA >115 g/m2 in men and >95 in women) according to 2024 ESC Guidelinessurrogate

Main Result

Odds Ratio: 2.162 (95% CI 1.32–3.64)

p-value: p=0.0042

Limitations

Unable to establish a causal relationship between MFN2 and hypertension-mediated LVH due to study design.
Did not investigate MFN2 gene expression to provide conclusions about cause-effect relationships.
Included only Caucasian patients from a single center, limiting generalizability to other ethnic groups.
Not designed to investigate the prevalence of MFN2 polymorphisms in subjects without hypertension.
Cross-sectional design precludes establishing a causal relationship between MFN2 and LVH.
No investigation of MFN2 gene expression to establish cause-effect relationships.
Adjustment for BMI might have played a role in the loss of significance for LV mass/height2.7 at covariate analysis.

Implication

Specific Mitofusin 2 genetic variants are independently associated with an increased risk of left ventricular hypertrophy in patients with essential hypertension, suggesting mitochondrial dysfunction contributes to hypertensive cardiac structural remodeling.

Abstract

Previous experimental studies showed that dysfunctions of mitofusin 2 (Mfn2), a mitochondrial dynamin-related protein, are associated with the presence of left ventricular hypertrophy (LVH). We examined the association of MFN2/rs2336384 and MFN2/rs2236057 polymorphic variants with the presence of LVH in three-hundred-forty-five patients with essential hypertension. One-hundred-thirteen individuals (33%) presented LVH. Hypertensive patients carrying the GG genotype at the MFN2/rs2336384 had a significant increase of echocardiographically-assessed septal thickness, posterior wall thickness, relative wall thickness (RWT), LV mass/ body surface area (BSA) (p = 0.001), LV mass/height2, and left atrium volume index (LAVi) compared to subjects carrying either TT or TG genotypes. These results were confirmed after adjustment for age, gender, body mass index (BMI), office blood pressure (BP), antihypertensive treatment with a combination of two or more drugs and the number of BP-lowering agents. With regard to MNF2/rs2236057, hypertensive subjects carrying the mutant A allele had a significant increase of septal thickness, posterior wall thickness, RWT, LV mass/BSA, LV mass/height2 and LAVi compared to wild-type homozygotes (GG genotype) and heterozygotes (GA genotype). After adjustment for covariates, the results were still significant for septal thickness, posterior wall thickness, LV mass/BSA and LAVi. Multivariable logistic regression analysis demonstrated that the carrier status of both G allele at rs2336384 and A allele at rs2236057 was associated with an increased risk of LVH. Our results demonstrate a significant association of MFN2 variants with LVH in hypertensives and highlight the potential role of MFN2-dependent mitochondrial dysfunction on increased susceptibility to cardiac damage in human hypertension. Relationship between Mitofusin 2 polymorphisms and left ventricular hypertrophy. CI, confidence interval; LVH, left ventricular hypertrophy; MFN2, mitofusion 2; OR, odds ratio.

Discussion

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Cite This Study

Gallo et al. (2026) conducted a cross-sectional in Essential hypertension (n=345). MFN2/rs2336384 G allele vs. Non-carriers (TT or TG genotypes) was evaluated on Risk of left ventricular hypertrophy (LVH) (OR 2.162, 95% CI 1.32-3.64, p=0.0042). Carrier status of the G allele at MFN2/rs2336384 was significantly associated with an increased risk of left ventricular hypertrophy in hypertensive patients (OR 2.162).

synapsesocial.com/papers/6ad115a000741cc3fba7d6d0 https://doi.org/10.1038/s41371-026-01208-8

Topics

Hypertension management

Echocardiography

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Mitofusin 2 polymorphic variants and left ventricular hypertrophy in human hypertension

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Mitofusin 2 polymorphic variants and left ventricular hypertrophy in human hypertension

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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Topics

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