Publications by authors named "Maximiliano Ruiz-Galdon"

13 Publications

  • Page 1 of 1

MAOB rs3027452 Modifies Mood Improvement After Tryptophan Supplementation.

Int J Gen Med 2021 6;14:1751-1756. Epub 2021 May 6.

Department of Surgery, Biochemistry and Immunology School of Medicine, University of Malaga, Malaga, Spain.

Purpose: Tryptophan is the only precursor of serotonin, the hormone which helps regulate key human functions such as appetite, memory, mood, and sexual behavior. Connections have been identified between serotonin system dysfunction and the molecular etiology and treatment of mood disorders in a wide range of studies. Proposals have been put forward to co-administer tryptophan supplementation together with serotonin reuptake inhibitors in major depression patients, and also to exploit the sub-therapeutic depressive status in healthy populations. The reported responses, however, have been very dissimilar and this uneven effect may largely be explained by interindividual genetic differences.

Materials And Methods: We studied mood change in 138 healthy subjects using both Goldberg's General Health Questionnaire and the Profile of Mood States Questionnaire to determine the effects of a daily supplementation of 1g of tryptophan or placebo. Buccal DNA samples were provided and (rs1800532), (rs3788862 and rs979605), (rs3027452), and (rs6269 and rs4680) variants were genotyped.

Results: rs3027452 was equally associated with tryptophan supplementation efficacy in the depression subscales of both questionnaires (ΔT-Score.D; ΔT-Score.TMD and ΔPOMS.D p-values <0.01).

Conclusion: Here we provide evidence that tryptophan supplementation has an uneven effect on mood improvement in the general population.
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May 2021

Measurement of Serum Testosterone in Nondiabetic Young Obese Men: Comparison of Direct Immunoassay to Liquid Chromatography-Tandem Mass Spectrometry.

Biomolecules 2020 12 19;10(12). Epub 2020 Dec 19.

Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain.

Hypoandrogenemia, a frequent finding in men with obesity, is defined by low concentrations of serum testosterone. Although immunoassay (IA) is the most used method for the determination of this steroid in clinical practice, liquid chromatography-mass spectrometry (LC-MS/MS) is considered a more reliable method. In this study, we aimed to compare IA versus LC-MS/MS measurement for the diagnosis of hypoandrogenemia in a cohort of 273 nondiabetic young obese men. Mean total testosterone (TT) levels were 3.20 ± 1.24 ng/mL for IA and 3.78 ± 1.4 ng/mL for LC-MS/MS. 53.7% and 26.3% of patients were classified as presenting hypoandrogenemia with IA and LC-MS/MS, respectively. Considering LC-MS/MS as the reference method, sensitivity and specificity of IA were 91.4% (95% CI 82.3-96.8) and 61.1% (95% CI 54.0-67.8), respectively. IA presented an AUC of 0.879 (95% CI 0.83-0.928). Multivariate regression analysis indicated that sex hormone-binding globulin (SHBG) concentrations ( = 0.002) and insulin resistance ( = 0.008) were factors associated with discrepant IA values. In conclusion, the determination of TT by IA in nondiabetic young men with obesity yields lower concentrations of TT than LC-MS/MS, resulting in an equivocal increased diagnosis of hypoandrogenemia, which could lead to inaccurate diagnosis and unnecessary treatment.
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December 2020

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

Mol Genet Genomic Med 2020 01 19;8(1):e1040. Epub 2019 Nov 19.

Department of Surgery, Biochemistry and Immunology, School of Medicine, University of Malaga, Málaga, Spain.

Background: 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.

Methods: In 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/m 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 CI [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.

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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January 2020

Effects of SHBG rs1799941 Polymorphism on Free Testosterone Levels and Hypogonadism Risk in Young Non-Diabetic Obese Males.

J Clin Med 2019 Jul 31;8(8). Epub 2019 Jul 31.

Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29010 Málaga, Spain.

Introduction: Obesity has been associated with increased risk of presenting hypogonadism. Free testosterone (FT) is the fraction of testosterone that carries out the biological function of testosterone, and is determined from total testosterone (TT) and sex-hormone binding globulin (SHBG) levels. We aimed to study the SHBG polymorphism rs1799941 in a cohort of young non-diabetic obese males to unravel the possible implication of this polymorphism in obesity-related hypogonadism.

Methodology: 212 young (<45 years) non-diabetic obese (BMI ≥ 30 kg/m) males participated in this study. Subjects were classified according to TT and FT levels in: Eugonadal ( 55, TT > 3.5 ng/mL and FT ≥ 70 pg/mL; EuG), normal FT hypogonadism ( 40, TT < 3.5 and FT ≥ 70 pg/mL; normal FT HG) and hypogonadism ( 117, TT < 3.5 ng/mL and TL < 70 pg/mL; HG). The SHBG rs1799941 polymorphism (GG/GA/AA) was analyzed using the Taqman Open Array (Applied biosystem).

Results: The rs1799941 frequencies were different among the groups. Higher proportion of the allele (A) was found in HG, compared to EuG and normal FT HG. Among the genotypes, the rare homozygous (AA) were found in the normal FT HG group and higher levels of serum SHBG and lower of FT were observed. The presence of the allele A was related (according to lineal regression models) to an increased of SHBG levels ((GA) β = 3.28; (AA) β = 12.45) and a decreased of FT levels ((GA) β = -9.19; (AA) β = -18.52). The presence of the allele (A) increased the risk of presenting HG compared to normal FT HG (OR = 2.54).

Conclusions: The rs1799941 of the SHBG gene can partially determine the presence of obesity-related hypogonadism in young non-diabetic males and whether these subjects have normal FT HG.
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July 2019

Dysmorphic contribution of neurotransmitter and neuroendocrine system polymorphisms to subtherapeutic mood states.

Brain Behav 2019 02 17;9(2):e01140. Epub 2019 Jan 17.

Department of Surgery, Biochemistry and Immunology, School of Medicine, University of Malaga, Malaga, Spain.

Objective: From an evolutionary perspective, emotions emerged as rapid adaptive reactions that increase survival rates. Current psychobiology includes the consideration that genetic changes affecting neuroendocrine and neurotransmission pathways may also be affecting mood states. Following this hypothesis, abnormal levels of any of the aminergic neurotransmitters would be of considerable importance in the development of a pathophysiological state.

Materials And Methods: A total of 668 students from the School of Medicine of the University of Malaga (Average = 22.41 ± 3; 41% men) provided self-report measures of mood states using POMS and GHQ-28 questionnaires and buccal cells for genotyping 19 polymorphisms from 14 selected neurotransmitter pathways genes (HTR1A; HTR2A; HTR2C; HTR3B; TPH1; SLC18A1; SLC18A2; COMT; MAOA; MAOB) and neuroendocrine system (AVPR1B; OPRM1; BDNF; OXTR).

Results: MAOA rs3788862 genotype correlates with decreasing levels of Tension among females (beta = -0.168, p-value = 0.003) but it is neutral among males in this subscale. On the contrary, it correlates with lower GHQ-28 depression scores among males (beta = -0.196, p-value = 0.008). Equivalently, SLC18A1 and HTR2A variants correlated with anger and vigor scores, only among males. From the neuroendocrine system, OPRM1 rs1799971 correlated increasing levels of female's Anxiety, depression and Social Dysfunction scores.

Conclusion: Our findings suggest that these polymorphisms contribute to define general population mood levels, although exhibiting a clear sexual dimorphism.
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February 2019

Sperm count and motility are quantitatively affected by functional polymorphisms of HTR2A, MAOA and SLC18A.

Reprod Biomed Online 2018 May 2;36(5):560-567. Epub 2018 Feb 2.

Department of Biochemistry, Molecular Biology and Immunology, Faculty of Medicine, University of Malaga, 29071, Malaga, Spain. Electronic address:

Spermatozoa and neurones share similar membrane characteristics and features. Associations of multiple polymorphisms traditionally related to neurotransmission were investigated. Infertile men were grouped into controls with normospermia (n = 182) and idiopathic infertile men with asthenozoospermia (n = 103), and analysed as a case-control study and as a quantitative association of each genotype. Ten neurotransmission-associated genetic variants were mapped by SNP analysis using quantitative polymerase chain reaction with TaqMan probes. Men with HTR2A rs6313 had a higher risk of asthenozoospermia (OR = 2.14; P = 0.04). MAOA rs3788862 G carriers displayed an increased risk of asthenozoospermia (OR = 2.29; P = 0.02). The SLC18A1 rs1390938 G allele was more frequent among such cases (0.75 versus 0.87; P < 0.01 and P < 0.01 for Armitage trend test); for SLC18A1 rs2270641 P = 0.02 (case-control frequency) and P = 0.01 (Armitage trend test). MAOA rs3788862 was correlated with sperm motility (Spearman ρ = 0.14; P = 0.02); SLC18A1 rs1390938 was correlated with sperm count and motility (Spearman ρ = 0.20; P < 0.01). Gene polymorphisms of HTR2A, MAOA and SLC18A1, related to neurotransmission, are individually associated with asthenozoospermia through variation in sperm count and motility, without detectable allelic or genotype interaction.
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May 2018

Fetal alpha 5-reductase Val89Leu mutation is associated with late miscarriage.

Reprod Biomed Online 2017 Jun 21;34(6):653-658. Epub 2017 Mar 21.

Department of Biochemistry, Molecular Biology and Immunology, Faculty of Medicine, University of Malaga, 29071 Malaga, Spain. Electronic address:

The present study was undertaken to determine the role of different polymorphisms affecting the testosterone/oestrogen pathway in miscarriage. Alpha 5-reductase (SRD5A2) rs523349 and rs9282858, cytochrome P450 aromatase (CYP19A1) rs4646, rs10046 and rs2236722 and oestrogen receptor (ESR1) rs9340799, rs2234693 and rs6932902 polymorphisms were selected. The case group consisted of 94 samples of formalin-fixed and paraffin-embedded fetal tissue from a miscarriage at ≤24 weeks. The control group comprised a population of 331 young healthy subjects. Only those single nucleotide polymorphisms (SNPs) fitting the Hardy-Weinberg equilibrium (n = 4) and euploid miscarriage samples (n = 67) were included for downstream analysis. Interestingly, SRD5A2 rs523349 (Val89Leu) was significantly associated with the risk of undergoing miscarriage after Bonferroni correction (odds ratio = 11.245, P < 2.2 × 10). Moreover, when Mantel-Cox regression analysis was performed, we observed that the effect was significantly constrained to the second trimester (P = 0.024, log rank). These results are compatible with an imbalance of testosterone/dihydrotestosterone, associated with a higher risk of miscarriage, especially in late pregnancy.
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June 2017

Differential behavior of serum and red blood cell folate during a treatment with levofolinic acid. Gender differences.

Clin Lab 2014 ;60(9):1579-84

Background: Folates are essential nutrients that maintain nucleotide synthesis and methylation reactions. Folate levels depend essentially on the diet. In the present work, the changes in the folate-homocysteine (Hcy) metabolic axis were studied in response to treatment with levofolinic acid.

Methods: 49 college students (23 men and 26 women) underwent a treatment voluntarily with 5 mg/day levofolinic acid for one month. Serum and red blood cell folate, vitamin B12, and Hcy levels were determined on days 2, 5, 10, and 30 during treatment and 30 days after completion of treatment.

Results: Serum folate and Hcy levels showed a plateau beginning on day 10, while red blood cell folate increased towards treatment completion. Gender differences were found in basal levels of Hcy, these differences remaining until the 10th day of treatment and reappearing 30 days after the treatment was finished. Between gender differences in treatment evolution were found only in percentage changes in red blood cell folate in women and men at day 30 of treatment.

Conclusions: There is a compartmentalization of folates in the body that presents a plateau in serum and an erythrocyte reservoir. Folate metabolism presents differential features between genders. The greater physiological need for folate in women of childbearing age could be the determining factor in this difference.
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October 2014

Genetic polymorphisms of serotonin transporter and receptor 1A could influence success during embryo implantation and maintenance of pregnancy.

Fertil Steril 2013 Jun 13;99(7):2009-16.e2. Epub 2013 Mar 13.

Instituto de Fertilidad Clínica Rincón, IVF Laboratory and I+D+i Unit, Malaga, Spain.

Objective: To explore whether serotonin-related gene polymorphisms influence clinical outcomes of IVF treatment in recipients using donated oocytes.

Design: Nested case-control study.

Setting: University-affiliated infertility clinic.

Patient(s): Two hundred forty-five women undergoing IVF treatment with donated oocytes.

Intervention(s): None.

Main Outcome Measure(s): Genotype and haplotype analysis of the serotonin transporter-linked polymorphic region (5-HTTLPR), rs1800532, rs6295, rs6313, and rs3813929, between recipients grouped according to the results of the oocyte donation for IVF treatment.

Result(s): No differences were found between genotype distribution of the tryptophan hydroxylase 1, serotonin receptor 2A, and serotonin receptor 2C polymorphisms. Recipients carrying the LL genotype for 5-HTTLPR had lower clinical pregnancy rates (PR) and higher biochemical pregnancy loss (BPL) events. Lower implantation rates were found in CC carriers for 5-HT1A.rs6295 who also presented higher BPL rates. A lower incidence of clinical pregnancy was observed for LC haplotypes, corresponding to an increase in BPL rates.

Conclusion(s): A strong association was found between early pregnancy loss and recipients carrying the 5-HTTLPR and rs6295 genetic variants. Identifying biological processes involving serotonin and embryo implantation may help to understand the dynamics of the maternal-embryo dialogue.
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June 2013

Genetic polymorphisms in folate pathway enzymes, DRD4 and GSTM1 are related to temporomandibular disorder.

BMC Med Genet 2011 May 26;12:75. Epub 2011 May 26.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Málaga, Spain.

Background: Temporomandibular disorder (TMD) is a multifactorial syndrome related to a critical period of human life. TMD has been associated with psychological dysfunctions, oxidative state and sexual dimorphism with coincidental occurrence along the pubertal development. In this work we study the association between TMD and genetic polymorphisms of folate metabolism, neurotransmission, oxidative and hormonal metabolism. Folate metabolism, which depends on genes variations and diet, is directly involved in genetic and epigenetic variations that can influence the changes of last growing period of development in human and the appearance of the TMD.

Methods: A case-control study was designed to evaluate the impact of genetic polymorphisms above described on TMD. A total of 229 individuals (69% women) were included at the study; 86 were patients with TMD and 143 were healthy control subjects. Subjects underwent to a clinical examination following the guidelines by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Genotyping of 20 Single Nucleotide Polymorphisms (SNPs), divided in two groups, was performed by multiplex minisequencing preceded by multiplex PCR. Other seven genetic polymorphisms different from SNPs (deletions, insertions, tandem repeat, null genotype) were achieved by a multiplex-PCR. A chi-square test was performed to determine the differences in genotype and allelic frequencies between TMD patients and healthy subjects. To estimate TMD risk, in those polymorphisms that shown significant differences, odds ratio (OR) with a 95% of confidence interval were calculated.

Results: Six of the polymorphisms showed statistical associations with TMD. Four of them are related to enzymes of folates metabolism: Allele G of Serine Hydoxymethyltransferase 1 (SHMT1) rs1979277 (OR = 3.99; 95%CI 1.72, 9.25; p = 0.002), allele G of SHMT1 rs638416 (OR = 2.80; 95%CI 1.51, 5.21; p = 0.013), allele T of Methylentetrahydrofolate Dehydrogenase (MTHFD) rs2236225 (OR = 3.09; 95%CI 1.27, 7.50; p = 0.016) and allele A of Methionine Synthase Reductase (MTRR) rs1801394 (OR = 2.35; 95CI 1.10, 5.00; p = 0.037). An inflammatory oxidative stress enzyme, Gluthatione S-Tranferase Mu-1(GSTM1), null allele (OR = 2.21; 95%CI 1.24, 4.36; p = 0.030) and a neurotransmission receptor, Dopamine Receptor D4 (DRD4), long allele of 48 bp-repeat (OR = 3.62; 95%CI 0.76, 17.26; p = 0.161).

Conclusions: Some genetic polymorphisms related to folates metabolism, inflammatory oxidative stress, and neurotransmission responses to pain, has been significantly associated to TMD syndrome.
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May 2011

[Mild hyperhomocysteinemia, low folate levels and prognosis of acute coronary syndrome without ST elevation].

Med Clin (Barc) 2007 Sep;129(8):281-6

Servicio de Cardiología, Hospital Universitario Virgen de la Victoria, Málaga, España.

Background And Objective: The influence of homocysteine metabolism on the prognosis of acute coronary syndrome without ST elevation is controversial.

Patients And Method: Prospective study of 109 patients admitted because of acute coronary syndrome without ST elevation. Basal plasmatic levels of homocysteine and folates were obtained. Clinical features and survival data on follow-up were registered.

Results: Both two years-free-of-events and total survival were lower in patients with low folate levels (36.5% vs 72.5%, p = 0.02; 48% vs 94%, p < .001). Patients with high homocysteine levels had lower two years-free-of-events survival (57.4% vs 89.1%, p < .01); but no difference in the total survival was observed (86.3% vs 97.3%, p = 0.11). The multivariate analysis showed that low folate levels was an independent predictor of mortality (odds ratio [OR] = 8.33; 95% confidence interval [CI], 1.88-33.33; p < 0.01), and moderate high homocysteine was an independent predictor of events on follow-up (OR = 4.34; 95% CI, 1.47-12.50; p < 0.01).

Conclusions: Patients with high homocysteine or low folate levels have a poor prognosis compared with those with normal levels. On the other hand, low folate levels and moderate hyiperhomocysteinemia are independent predictors of bad prognosis in the follow-up.
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September 2007

Influence of high homocysteine and low folate plasmatic levels in medium-term prognosis after acute coronary syndromes.

Int J Cardiol 2007 May 4;118(2):220-6. Epub 2006 Oct 4.

Cardiology Department, Hospital Universitario Virgen de la Victoria, School of Medicine, University of Malaga, Spain.

Background: To test prospectively whether moderate hyperhomocysteinemia and low folate levels could have an influence in the prognosis of 155 patients who presented with an acute coronary syndrome.

Methods And Results: After a mean follow-up of 13.4+/-7.4 months, patients with low folate levels had higher percentages of cardiovascular death and major cardiovascular events (33% vs. 5%, p<0.001; 44% vs. 22%, p<0.05) and patients with high homocysteine levels had a higher percentage of major cardiovascular events (31% vs. 14.5%, p<0.03). Kaplan-Meier survival estimates analysis showed that patients with low folate levels had a significantly higher probability of cardiovascular death and lower free-of-events survival (log rank statistic: 21.17, p<0.001 and 6.59, p=0.01). Patients with high homocysteine levels had a lower free-of-events survival (log rank statistic: 4.95, p=0.02). Different survival multivariate analysis model showed that the presence of low folate levels was an independent predictor of cardiovascular death (hazard ratio 8.85, 95% confidence interval 2.6-29.3, p<0.000) and high homocysteine levels was identified as independent predictor of major cardiovascular events (hazard ratio 2.34, 95% confidence interval 1.07-5.12, p<0.03).

Conclusions: Low folate levels and moderate hyperhomocysteinemia were identified as independent predictors of cardiovascular events in the follow-up.
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May 2007

[Collagen synthesis and heart failure].

Rev Esp Cardiol 2005 Aug;58(8):975-8

Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain.

Little is known about collagen metabolism in heart failure, with or without left ventricular systolic dysfunction. We studied serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type-I synthesis, and of the carboxy-terminal telopeptide of collagen type I (ICTP), a marker of collagen type-I degradation, in 70 patients admitted for heart failure (35 with depressed left ventricular systolic function and 35 with preserved left ventricular systolic function) and in 30 control subjects. Patients with kidney failure, liver disease, metabolic bone disease, rheumatic disease, recent (within 3 months) major trauma or surgery, or serious wounds were excluded. The concentration of the collagen synthesis marker, PIP, was higher in heart failure patients than control subjects, at 140+/-56.38 mg/L vs 113.66+/-36.6 microg/L, respectively (P=.01). However, there was no difference in the concentration of the collagen degradation marker, ICTP, between heart failure patients and control subjects, at 2.89+/-2.37 mg/L vs 2.26+/-1.7 microg/l, respectively. In heart failure patients, left ventricular systolic function had nonsignificant effect on the PIP or ICTP concentration.
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August 2005