Mitofusin 2 polymorphic variants and left ventricular hypertrophy in human hypertension

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.