Monoamino oxidase alleles correlate with the presence of essential hypertension among hypogonadic patients.

José Luis Royo,Fernando Cardona,Daniel Castellano‐Castillo,Maximiliano Ruiz‐Galdon,José C. Fernández‐García,María Molina‐Vega,Francisco J. Tinahones,Armando Reyes‐Engel

doi:10.1002/mgg3.1040

Abstract

BackgroundMonoamine oxidase (MAO) activity has been traditionally implicated in blood pressure through its effects on biogenic amine levels such as catecholamines, serotonin, and dopamine. Nowadays, this role is considered relegated to side‐effects such as orthostatic hypotension and/or hypertensive crisis derived from MAO‐inhibitory treatments in patients with psychiatric disease.MethodsIn the present work we have found an association between a polymorphic variant of MAOB gene and arterial hypertension in obese hypogonadic patients. The study cases comprised a series of 219 nondiabetic males with a body mass index ≥30 kg/m2 and aged <45 years. Hypogonadism was defined as subnormal testosterone concentrations, when free testosterone values ranged <65 pg/ml.Results MAOB rs3027452‐A allele carriers were significantly over‐represented among hypertensive (HT) patients (25.49%) in comparison to either the non‐HT patients (10%, OR = 3.079 CI95 [1.364–6.952], p = .005, Chi‐square test) and the control population series of nonobese nor hypogonadic males (also 10%, p = .003 Chi‐square test). Upon adjusted, an independent association was shown with the hypogonadic group with hypertension when compared with nonhypertensive hypogonadics (Beta = 3.653, p = .005). When quantitative analysis was performed, hypertensive patients harboring rs3027452‐A allele showed higher systolic blood pressure values (p = .038, Mann–Whitney U‐test) as well as an increased Systolic‐Diastolic range despite following HT treatment (∆mmHg 54 vs. 48 for rs3027452‐A and rs3027452‐G respectively, p‐value .019, Mann–Whitney U‐test). Previous studies on MAOB revealed that rs3027452‐A allele has been correlated to a lower activity of the enzyme, what gives a functional evidence over our observation.ConclusionIf this result could be extrapolated to other hypertensive patient groups, it would implicate a review of the markers and therapeutic targets on human hypertension.

Highlights

Monoamine oxidases A and B (MAOA OMIM 309850 and MAOB OMIM 309860) genes are both located in the short arm of the X chromosome (Xp.11.4‐11.3), showing in addition a high degree of homology (Sims et al, 1992)
We have evaluated the distribution of MAOA and MAOB polymorphisms among a hypogonadic population
When the hypogonadic population was stratified according to the hypertensive status we found that rs3027452‐A carriers were significantly over‐represented among hypertensive (HT) patients (25.49%) in comparison to either the non‐HT patients (10%, p = .005, Chi‐square test) and the control population series of nonobese nor hypogonadic males

Summary

Introduction

Monoamine oxidases A and B (MAOA OMIM 309850 and MAOB OMIM 309860) genes are both located in the short arm of the X chromosome (Xp.11.4‐11.3), showing in addition a high degree of homology (Sims et al, 1992) These two genes codify for two enzymes, MAOA and MAOB, which carry out their function, mainly the degradation of bioamines such as serotonin (5‐hydroxytryptamine or 5‐HT), dopamine, and noradrenaline (Greenawalt & Schnaitman, 1970), on the external side of the mitochondrial membrane. Monoamine oxidase (MAO) activity has been traditionally implicated in blood pressure through its effects on biogenic amine levels such as catecholamines, serotonin, and dopamine. Nowadays, this role is considered relegated to side‐effects such as orthostatic hypotension and/or hypertensive crisis derived from MAO‐inhibitory treatments in patients with psychiatric disease. Conclusion: If this result could be extrapolated to other hypertensive patient groups, it would implicate a review of the markers and therapeutic targets on human hypertension

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Results

Conclusion