Actinomycetes Associated with Arthropods as a Source of New Bioactive Compounds.

Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the drug industry pipeline. Different strategies have been pursued to increase the chances of discovering new molecules, such as studying underexplored environments like arthropod symbionts, which represent a relevant reservoir for active metabolites. This review summarizes recent research on the identification of bioactive molecules produced by Actinomycetes associated with arthropods' microbiome. The metabolites have been categorized based on their structural properties and host, highlighting that multidisciplinary approaches will be the key to fully understanding this complex relationship.

Patterns of Alcohol Use in Hispanic Individuals with TBI over the Ten Years Post-Injury: A Model Systems Study.

The study's aim was to examine alcohol consumption patterns and predictors of consumption across time among Hispanics with traumatic brain injury (TBI) in the U.S. within ten years post-injury. This longitudinal cohort study included 1342 Hispanic individuals (77.6% males) from the multi-site, longitudinal TBI Model Systems (TBIMS) database. The main outcome measures were consumption information, demographic, and injury characteristics. Across the full sample, alcohol consumption variables generally demonstrated quadratic movement characterized by an initial increase followed by a plateau or slight decrease over the ten years post-injury. The predictors of higher consumption were being men, single, with a history of excessive alcohol use, with a nonviolent mechanism of injury, shorter duration of PTA, and higher levels of education. Participants had a greater number of 5+ drinks/episode occurrences in the past month if they were men and had had a greater number of 5+ drinks/episode occurrences in the month before injury. There was no differential change in alcohol consumption over time as a function of these predictors. This study identified a profile of at-risk Hispanics with TBI for increased alcohol consumption. These individuals should be identified and targeted for early evidence-based alcohol intervention after TBI when results might be most favorable.

Cómo estimar la composición corporal en la enfermedad de Huntington. Estudio transversal y observacional con bioimpedancia de múltiples frecuencias / How to estimate body composition in Huntington’s disease. A cross-sectional, observational study using multiple frequencies bioimpedance

Introducción La enfermedad de Huntington (EH) es un trastorno raro neurodegenerativo. La información fiable del estado nutricional, especialmente de la composición corporal, es crítica en clínica y en investigación. La facilidad de aplicación y portabilidad del análisis de la bioimpedancia de múltiples frecuencias (mfBIA) la convierten en una herramienta atractiva para medirla, pero se desconoce su precisión en la EH. Objetivo Evaluar la precisión del mfBIA frente a la absorciometría dual de rayos X (DEXA) en la EH. Pacientes y métodos Estudio transversal, observacional y unicéntrico. La EH se midió con la subescala motora de la escala unificada de valoración de la EH y con la capacidad funcional total. La composición corporal se valoró según la masa libre de grasa (MLG), la masa grasa (MG), el índice de masa libre de grasa (IMLG) y el índice de masa grasa (IMG). Se utilizó el coeficiente de correlación intraclase con intervalos de confianza al 95% y estimaciones de sesgo mediante gráficos de Bland-Altman. Resultados Se incluyó a 16 pacientes, siete hombres y nueve mujeres, con edad media de 58,5 (32-68) años, capacidad funcional total de 10 (3-13) y escala unificada de valoración de la EH de 31 (7-85). La fiabilidad era alta entre el mfBIA y la DEXA para el IMLG en hombres, 0,88 (intervalo de confianza al 95%: 0,17-0,98), y mujeres, 0,9 (intervalo de confianza al 95%: 0,61-0,98); y para el IMG en hombres, 0,97 (intervalo de confianza al 95%: 0,83-0,99), y mujeres, 0,91 (intervalo de confianza al 95%: 0,68-0,98). El mfBIA sobreestimó ligeramente la MLG, la MG, el IMG y el IMLG en los hombres, pero subestimó el IMLG en las mujeres. Conclusiones El mfBIA es un método fácil de usar, seguro, no invasivo y preciso para medir la composición corporal y el estado nutricional en pacientes con EH leve-moderada. (AU)

INTRODUCTION Huntington´s disease (HD) is a rare neurodegenerative disorder. Reliable information about nutritional status, especially body composition from individuals with HD is critical for clinical care and research. The ease of application and portability of multiple frequencies bioelectrical impedance analysis (mfBIA) make it an attractive tool for measuring body composition, but its accuracy in HD is unknown. AIM To evaluate the accuracy of mfBIA vs. Dual X-ray absorptiometry (DEXA) in HD. PATIENTS AND METHODS Cross-sectional, observational, and single-center study. HD severity was measured using motor subscale of the unified Huntington´s disease rating scale (m-UHDRS) and the total functional capacity (TFC). Body composition was measured in terms of fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI). Using Bland-Altman plots, we analyzed reliability between DEXA and mfBIA using the Intraclass Correlation Coefficient with 95% confidence intervals (CI) and bias estimates for all. RESULTS We included 16 patients with HD, 7 men, and 9 women, median age of 58.5 (32;68) years, TFC: 10 (3;13), and m-UHDRS: 31 (7;85). The reliability between mfBIA and DEXA were high for FFMI in men: 0.88 (95% CI 0.17-0.98), and women: 0.90 (95% CI 0.61- 0.98); for FMI, men: 0.97 (95% CI 0.83-0.99), and women: 0.91 (95% CI 0.68-0.98). Compared to DEXA, mfBIA slightly overestimated FFM, FM, FMI and FFMI in men and underestimated FFMI in women. CONCLUSIONS mfBIA is an easy-to-use, safe, non-invasive, accurate method for measuring body composition and nutritional status in patients with mild-moderate HD. (AU)

Sex significantly predicts medial temporal volume when controlling for the influence of ApoE4 biomarker and demographic variables: A cross-ethnic comparison.

OBJECTIVE: To explore the relationship between age, education, sex, and ApoE4 (+) status to brain volume among a cohort with amnestic mild cognitive impairment (aMCI). METHOD: One hundred and twenty-three participants were stratified into Hispanic (n = 75) and White non-Hispanic (WNH, N = 48). Multiple linear regression analyses were conducted with age, education, sex, and ApoE4 status as predictor variables and left and right combined MRI volumes of the hippocampus, parahippocampus, and entorhinal cortex as dependent variables. Variations in head sizes were corrected by normalization with a total intracranial volume measurement. RESULTS: Bonferroni-corrected results indicated that when controlling for ApoE4 status, education, and age, sex was a significant predictor of hippocampal volume among the Hispanic group (ß = .000464, R2 = .196, p < .01) and the WNH group (ß = .000455, R2 = .195, p < .05). Education (ß = .000028, R2 = .168, p < .01) and sex (ß = .000261, R2 = .168, p < .01) were significant predictors of parahippocampal volume among the Hispanic MCI group when controlling for the effects of ApoE4 status and age. One-way ANCOVAs comparing hippocampal and parahippocampal volume between males and females within groups revealed that females had significantly larger hippocampal volumes (p < .05). Hispanic females had significantly larger hippocampal (p < .001) and parahippocampal (p < .05) volume compared to males. No sex differences in parahippocampal volume were noted among WNHs. CONCLUSIONS: Biological sex, rather than ApoE4 status, was a greater predictor of hippocampal volume among Hispanic and WNH females. These findings add to the mixed literature on sex differences in dementia research and highlight continued emphasis on ethnic populations to elucidate on neurodegenerative disparities.

Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post-surgical pain.

Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post-anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC-MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p < 0.001 and 0.020, multivariate p < 0.001 and 0.001, unstandardized ß coefficients = 0.386 and 0.346, R2 = 0.146 and 0.120, respectively). CYP2B6 PMs (n = 10) were significantly related to a higher reduction in pain 30 min after tramadol intake (univariate p = 0.038, multivariate p = 0.016, unstandardized ß coefficient = 0.224, R2 = 0.178), to lower PACU admission time (p = 0.007), and to lower incidence of adverse drug reactions (p = 0.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (p = 0.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of CYP3A4 genetic variation on tramadol response.

Matching an Old Marine Paradigm: Limitless Connectivity in a Deep-Water Fish over a Large Distance.

Investigations of population structuring in wild species are fundamental to complete the bigger picture defining their ecological and biological roles in the marine realm, to estimate their recovery capacity triggered by human disturbance and implement more efficient management strategies for fishery resources. The Blackspot Seabream (Pagellus bogaraveo, Brünnich 1768) is a commercially valuable deep-water fish highly exploited over past decades. Considering its exploitation status, deepening the knowledge of intraspecific variability, genetic diversity, and differentiation using high-performing molecular markers is considered an important step for a more effective stock assessment and fishery management. With one of the largest efforts conceived of and completed by countries overlooking the Atlantic and Mediterranean coasts in recent years, a total of 320 individuals were collected from different fishing grounds in the Mediterranean Sea and Atlantic Ocean and analysed using 29 microsatellite loci. We applied multiple statistical approaches to investigate the species' connectivity and population structure across most of its described distribution area. Considering the incomplete knowledge regarding the migratory behaviour of adults, here we suggest the importance of egg and larval dispersal in sustaining the observed genetic connectivity on such a large geographical scale.

Multimodal video and IMU kinematic dataset on daily life activities using affordable devices.

Human activity recognition and clinical biomechanics are challenging problems in physical telerehabilitation medicine. However, most publicly available datasets on human body movements cannot be used to study both problems in an out-of-the-lab movement acquisition setting. The objective of the VIDIMU dataset is to pave the way towards affordable patient gross motor tracking solutions for daily life activities recognition and kinematic analysis. The dataset includes 13 activities registered using a commodity camera and five inertial sensors. The video recordings were acquired in 54 subjects, of which 16 also had simultaneous recordings of inertial sensors. The novelty of dataset lies in: (i) the clinical relevance of the chosen movements, (ii) the combined utilization of affordable video and custom sensors, and (iii) the implementation of state-of-the-art tools for multimodal data processing of 3D body pose tracking and motion reconstruction in a musculoskeletal model from inertial data. The validation confirms that a minimally disturbing acquisition protocol, performed according to real-life conditions can provide a comprehensive picture of human joint angles during daily life activities.

Corrected analysis of "the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial" that accounts for clustering and nesting verifies conclusions.

In this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.

Technology caregiver intervention for Alzheimer's disease (I-CARE): Feasibility and preliminary efficacy of Brain CareNotes.

BACKGROUND: The primary aim of the current pilot study was to examine enrollment rate, data completion, usability, acceptance and use of a mobile telehealth application, Brain CareNotes. A secondary aim was to estimate the application's effect in reducing caregiver burden and behavioral and psychological symptoms related to dementia (BPSD). METHODS: Patient-caregiver dyads (n = 53) were recruited and randomized to intervention and control groups. Assessment of usability, acceptance, BPSD symptoms, and caregiver burden were collected at baseline, 3- and 6-month follow-up. RESULTS: The enrollment rate was acceptable despite pandemic related challenges (53/60 target recruitment sample). Among randomized individuals, there was a retention rate of 85% and data completion was attained for 81.5% of those allocated to usual care and 88.5% of those allocated to Brain CareNotes. Mean caregiver-reported app usability at 6 months was 72.5 (IQR 70.0-90.0) on the System Usability Scale-considered "Good to Excellent"-and user acceptance was reasonable as indicated by 85%-90% of caregivers reporting they would intend to use the app to some degree in the next 6 months, if able. Regarding intervention effect, although differences in outcome measures between the groups were not statistically significant, compared to baseline, we found a reduction of caregiver burden (NPI-Caregiver Distress) of 1.0 at 3 months and 0.7 at 6 months for those in the intervention group. BPSD (NPI Total Score) was also reduced from baseline by 4.0 at 3 months and by 0.5 at 6 months. CONCLUSIONS: Brain CareNotes is a highly scalable, usable and acceptable mobile caregiver intervention. Future studies should focus on testing Brain CareNotes on a larger sample size to examine efficacy of reducing caregiver burden and BPSD.

Combination of Soy Isoflavones, 8-Prenylnaringenin and Melatonin Improves Hot Flashes and Health-Related Quality of Life Outcomes in Postmenopausal Women: Flavie Study.

OBJECTIVES: This study aims to investigate the effects of a combination of soy isoflavones, 8-prenylnaringenin (8-PN), and melatonin in postmenopausal women suffering from moderate-to-severe hot flashes (HFs). METHODS: A multicenter, prospective, open-label study enrolled 44 postmenopausal women suffering from moderate-to-severe HFs (≥ 5 daily or ≥ 35 weekly) to receive 54.4 mg standardized soy isoflavones (including 24.5 mg genistein and 16.3 mg daidzein), 100 µg 8-PN, and 1 mg melatonin once daily for 12 weeks. The primary clinical outcomes included changes in health-related quality of life (HRQoL) scores (Menopause-Specific QoL questionnaire [MENQoL] and Cervantes Scale) and HFs following 4 and 12 weeks of treatment. Other analyses included treatment adherence, acceptability, tolerability, and safety. RESULTS: All of the four domains of MENQoL questionnaire significantly improved at 4 weeks (P < 0.05) and 12 weeks (P < 0.001), affecting significantly the vasomotor, psychosocial, and physical spheres (41.2%, 26.3%, and 25.0%; 12 weeks improvements, respectively). Similarly, in the menopause (39.3%) and psychic (51.7%) domains (both P < 0.05 at 12 weeks), the global score of the Cervantes Scale significantly increased at 4 weeks (18.6%) and 12 weeks (35.4%). Accordingly, moderate-to-severe HFs significantly decreased at 4 weeks compared to baseline (41.7% reduction) and further reduced at 12 weeks (76.5%), including the total number of episodes. CONCLUSIONS: Food supplements containing soy isoflavones, 8-PN, and melatonin showed an early and progressive benefit for reducing clinically significant HFs and for improving HRQoL across all domains, favorably affecting postmenopausal women's overall well-being.

Identification of clinical and pharmacogenetic factors influencing metformin response in Type 2 diabetes mellitus.

Metformin, a hypoglycemic drug for Type 2 diabetes mellitus, shows variability in pharmacokinetics and response due to membrane transporters. This study followed 34 Type 2 diabetes mellitus patients on metformin treatment. Genetic variants in 11 metformin transport-related genes were analyzed, revealing associations. Specifically, SLC47A1 rs2289669 A/A and SLC22A4 rs1050152 T/T genotypes correlated with glycated hemoglobin values at 6 months. SLC47A1 rs2289669 G/A genotype influenced glucose levels at 6 months, while SLC29A4 rs3889348 A/A, SLC47A1 rs2289669 A/A, SLC22A4 rs1050152 C/T and SLC47A2 rs12943590 A/A genotypes were linked to glucose levels at 12 months. Additionally, ABCB1 rs2032582 C/A and ABCG2 rs2231137 C/T genotypes impacted cholesterol levels at 12 months. These findings shed light on metformin response determinants, offering insights for further research.

Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives.

Multiple myeloma (MM) is a hematological neoplasm for which different chemotherapy treatments are used with several drugs in combination. One of the most frequently used drugs for the treatment of MM is the proteasome inhibitor bortezomib. Patients treated with bortezomib are at increased risk for thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, infection, and fatigue. This drug is almost entirely metabolized by cytochrome CYP450 isoenzymes and transported by the efflux pump P-glycoprotein. Genes encoding both enzymes and transporters involved in the bortezomib pharmacokinetic pathway are highly polymorphic. The response to bortezomib and the incidence of adverse drug reactions (ADRs) vary among patients, which could be due to interindividual variations in these possible pharmacogenetic biomarkers. In this review, we compiled all pharmacogenetic information relevant to the treatment of MM with bortezomib. In addition, we discuss possible future perspectives and the analysis of potential pharmacogenetic markers that could influence the incidence of ADR and the toxicity of bortezomib. It would be a milestone in the field of targeted therapy for MM to relate potential biomarkers to the various effects of bortezomib on patients.

Pharmacogenetics in the Treatment of Huntington's Disease: Review and Future Perspectives.

Huntington's disease (HD) is an autosomal dominant progressive brain disorder, caused by a pathological expansion of a CAG repeat that encodes the huntingtin gene. This genetic neurodegenerative rare disease is characterized by cognitive, motor, and neuropsychiatric manifestations. The aim of the treatment is symptomatic and addresses the hyperkinetic disorders (chorea, dystonia, myoclonus, tics, etc.) and the behavioural and cognitive disturbances (depression, anxiety, psychosis, etc.) associated with the disease. HD is still a complex condition in need of innovative and efficient treatment. The long-term goal of pharmacogenetic studies is to use genotype data to predict the effective treatment response to a specific drug and, in turn, prevent potential undesirable effects of its administration. Chorea, depression, and psychotic symptoms have a substantial impact on HD patients' quality of life and could be better controlled with the help of pharmacogenetic knowledge. We aimed to carry out a review of the available publications and evidence related to the pharmacogenetics of HD, with the objective of compiling all information that may be useful in optimizing drug administration. The impact of pharmacogenetic information on the response to antidepressants and antipsychotics is well documented in psychiatric patients, but this approach has not been investigated in HD patients. Future research should address several issues to ensure that pharmacogenetic clinical use is appropriately supported, feasible, and applicable.

Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers.

For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study on healthy participants. This is the first investigation to consider demographic characteristics alongside all transporters involved in metformin distribution. Pharmacokinetic parameters of metformin were found to be affected by age, sex, ethnicity, and several polymorphisms. Age and SLC22A4 and SLC47A2 polymorphisms affected the area under the concentration-time curve (AUC). However, after adjusting for dose-to-weight ratio (dW), sex, age, and ethnicity, along with SLC22A3 and SLC22A4, influenced AUC. The maximum concentration was affected by age and SLC22A1, but after adjusting for dW, it was affected by sex, age, ethnicity, ABCG2, and SLC22A4. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by SLC22A3. The volume of distribution and clearance was affected by sex, age, ethnicity and SLC22A3. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in ABCB1, SLC2A2, SLC22A2, or SLC47A1. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization.

Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model.

Previous clinical trials have shown that mesenchymal stromal cells (MSCs) can modulate graft versus host disease (GvHD) after allogeneic hematopoietic transplantation, although with variable efficacy. To improve the anti-GvHD effect of these cells, adipose tissue derived-human MSCs (Ad-MSCs) were transduced with a lentiviral vector conferring stable expression of CXCR4, a molecule involved in cell migration to inflamed sites, and IL-10, a cytokine with potent anti-inflammatory properties. In vitro experiments showed that the expression of these molecules in Ad-MSCs (named CXCR4-IL10-MSCs) efficiently enhanced their migration towards SDF-1α and also improved their immunomodulatory properties compared to unmodified Ad-MSCs (WT-MSCs). Moreover, using a humanized GvHD mouse model, CXCR4-IL10-MSCs showed improved therapeutic effects, which were confirmed by histopathologic analysis in the target organs. Additionally, compared to WT-MSCs, CXCR4-IL10-MSCs induced a more marked reduction in the number of pro-inflammatory Th1 and Th17 cells, a higher polarization towards an anti-inflammatory T cell profile (CD3+-IL10+ cells), and increased the number of regulatory T and B cells. Our in vitro and in vivo studies strongly suggest that CXCR4-IL10-MSCs should constitute an important new generation of MSCs for the treatment of GvHD in patients transplanted with allogeneic hematopoietic grafts.

Association Between Insulin-Like Growth Factor-1 and Social Cognition in Huntington's Disease.

Background: Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure. Objectives: To investigate the association of IGF-1 levels with social cognition and brain structure in Huntington's disease (HD). Methods: We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume-based voxel-based morphometry and surface-based cortical thickness pipeline. We analyzed the association of IGF-1 levels with social cognition and brain structure using adjusted regression analysis. Results: Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P = 0.02), and with lower IGF-1 levels (P = 0.04). In neuroimaging analyses, lower IGF-1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). Conclusions: In HD, abnormal IGF-1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.

Acculturation, Acculturative Stress, Adverse Childhood Experiences, and Intimate Partner Violence Among Latinx Immigrants in the US.

Latinx immigrants bear a disproportionate burden associated with intimate partner violence (IPV); however, efforts to develop evidence-based IPV prevention strategies and address health disparities have been impeded by a lack of understanding of the unique cultural (i.e., acculturation and acculturative stress) and socio-environmental (i.e., adverse childhood experiences [ACEs]) factors that contribute to IPV in this historically marginalized population. Guided by a contextual framework for IPV and a life-course perspective viewed through a gendered lens, this study aims to (a) identify relationships among acculturation, acculturative stress, ACEs, and IPV victimization and perpetration; and (b) explore whether profiles of IPV risk factors differ by gender (women vs. men) among Latinx immigrants. This cross-sectional, descriptive, correlational study was a secondary analysis of data from the baseline assessment of 331 ever-partnered Latinx immigrants aged 18 to 44 in a longitudinal study named Salud (Health), Estrés (Stress), y Resilencia (Resilency) (SER) Hispano. Logistic regressions adjusting for individual characteristics and gender subgroup analyses were used to address study aims. The majority of the participants were women (71.30%). More than half of all participants had experienced IPV victimization (57.70%) or IPV perpetration (60.73%). Latinx immigrants with higher family stress (adjusted odds ratio [aOR] = 1.16; p < .001) had an elevated risk for IPV victimization; those with more ACEs (aOR = 1.08; p = .005) had an increased risk for IPV perpetration. Women had a lower risk of IPV victimization (aOR = 0.45; p = .03) and a higher risk for IPV perpetration (aOR = 3.26; p = .001) compared to men. Although further research is warranted, the profiles of risk factors for IPV perpetration were different for women than for men. Culturally tailored preventions focused on acculturative stress and ACEs are needed to help Latinx immigrant communities minimize exposure to life-course adversities, improve positive adaptation to the US, and eliminate IPV-relevant health disparities.

Functional Variants in MicroRNAs (rs895819, rs11614913 and rs2910164) Are Associated with Susceptibility and Clinicopathological Features in Mexican Patients with Colorectal Cancer.

BACKGROUND: miRNAs are non-coding RNAs participating actively in the post-translational regulation of oncogenes, tumor suppressor, and DNA repair genes implicated in colorectal cancer (CRC). This study aims to examine the association of the variants miR-27a (rs895819 A>G), miR-196a2 (rs11614913 T>G) and miR-146a (rs2910164 C>G) in Mexican CRC patients. METHODS: DNA samples from 183 patients and 186 healthy Mexican subjects were analyzed. Variants were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) and adjusted by the Bonferroni test. RESULTS: Patients carrying the G/G genotype of the rs895819 variant in the miR-27a gene showed an increased risk of CRC (19% vs 12%, P=0.013). A similar tendency was noticed for patients younger than 50 years carrying A/G (48% vs 41%, P=0.014). The A/G genotype in TNM stages I+II (55.7% vs 40.8%, P=0.011) and tumor location in the colon (69.5 vs 40.8%, P=0.001) were also increased. For the variant rs11614913 of the miR-196a2 gene, carriers of the C/C genotype showed an increased risk of CRC (32% vs 22%, P=0.009). This genotype was more frequent in TNM stage III+IV (36.8% vs 22.5%, P=0.007) and the tumor had a more recurrent location in the rectum (31.6% vs 22.5%, P=0.013). The rs2910164 variant of the miR-146a gene was found to have no significant risk associations. CONCLUSION: Our results reveal that the rs895819 variant in miR-27a and rs11614913 in miR-196a2 have a substantial impact on the development of CRC.