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OBJECTIVE: Genetic variants of PON1, rs70587, rs662, rs854560, GSTM1, and GSTT1 and two single nucleotide polymorphisms (SNP) at 9p21.3 locus, rs1333049, and rs2383207; were evaluated in association with the risk for premature coronary artery disease (CAD) in a population of Yucatan, Mexico. These genes are involved in the inactivation of pro-oxidants and pro-inflammatory mediators, lipid and xenobiotic metabolism, detoxification of reactive oxygen species, and regulation of cellular proliferation playing key roles in the pathogenesis of atherosclerosis. METHODS: We conducted a matched case-control study with 98 CAD cases and 101 healthy controls. Genotyping of PON1 and 9p21.2 SNP was performed by real time-PCR and for GSTM1 and GSTT1 with multiplex-PCR. Odds ratios (OR) were calculated to estimate association and generalized multifactor dimensionality reduction (GMDR) algorithm to identify gene-gene and gene-environment interactions. RESULTS: The distribution of all allele/genotype frequencies in controls was within Hardy-Weinberg expectations (p > .05) except for GSTM1. The allele/genotype frequencies of the GSTT1 null were significantly higher in CAD cases than in controls, suggesting association with higher risk for developing CAD. The other SNPs did not show any significant independent association with premature CAD. GMDR revealed a significant interaction between GSTT1 and LL55 genotype. Likewise, the body mass index (BMI) and smoking also showed an interaction with GSTT1. CONCLUSION: The GSTT1 null allele/genotype is associated with an increased risk of developing premature CAD, the effect of which is not modified by cardiovascular risk factors in the population of Yucatan.
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Enfermedad de la Arteria Coronaria , Glutatión Transferasa/genética , Arildialquilfosfatasa/genética , Estudios de Casos y Controles , Cromosomas Humanos Par 9 , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , México/epidemiología , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
OBJECTIVES: High expression levels (HELs) of microRNA-122 (miR-122) or microRNA-222 (miR-222) have been associated with insulin resistance (IR), which leads to the development of obesity. The association between HELs of circulating miR-122 and miR-222 and the risk of obesity was evaluated in Mexican school-aged children, where childhood obesity is the primary cause of morbidity. METHODS: Anthropometric data, biochemical parameters, and caloric intake were obtained in 50 children with obesity and 49 children with normal weight. The expression of circulating miR-122 and miR-222 was measured by quantitative real-time polymerase chain reaction amplification. Data were analyzed using Student t test, Pearson correlation coefficient, associations with chi-square, and multiple linear and logistic regressions with SPSS software v.23. RESULTS: The mean relative expression for miR-122 and miR-222 was 0.33 and 5.65, respectively, for children with obesity and 0.22 and 3.16, respectively, for children with normal weight. The expression of miR-122 and miR-222 was 1.47 and 1.78-fold higher, respectively, in children with obesity (P = 0.001 and P = 0.025). HELs of both miR-122 and miR-222 were associated with body mass index (BMI), waist to height ratio (WHR), fat percentage, serum high-density lipid levels, triglycerides (TGs), and metabolic index (MI) (P < .001). CONCLUSIONS: The HELs of circulating miR-122 conferred a 3.85-fold increase in the risk for obesity, whereas the HELs of both miR-122 and miR-222 conferred a 3.11-fold increase in the risk for obesity, which were also associated with higher anthropometric or biochemical parameters, such as BMI, WHR, fat percentage, serum high-density lipid levels, TGs, and MI, in Mayan children.
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MicroARN Circulante , MicroARNs , Obesidad Infantil , Antropometría , Índice de Masa Corporal , Niño , Etnicidad , Humanos , México/epidemiología , MicroARNs/genética , Obesidad Infantil/etnología , Obesidad Infantil/genéticaRESUMEN
This article was published online with an error. Given names and family names of the authors were interchanged. The correct author names are presented above. The original article has been corrected.
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We report one complex paternity case presenting a presumable paternal four-step STR mutation between the alleged father (AF) and child; the complexity of the case required the AF-brother hypothesis to be discarded without including this DNA sample. A total of 23 autosomal STR loci included in the Powerplex Fusion® and Globalfiler™ kits confirmed one isolated mismatch for D22S1045 between the AF (17/17) and the male child (13/15) in the presence of the mother (15/15). In this case, the STR structure and father's age do not seem to have contributed to promote the observed multistep mutation. The Paternity Index (PI) based on 23 autosomal STRs did not favor the AF paternity over the AF-brother hypothesis based on a flat prior (PI = 0.1217; W = 10.85%). For that reason, we included 38 autosomal human identification (HID) insertions-deletions (indels) and 20 retrotransposon insertion polymorphisms (RIPs) contained in the InnoTyper® 21 kit. Although these biallelic markers favored the AF paternity rather than the AF-brother hypothesis (LR = 110.3; W = 99.1%), the global PI based on 81 autosomal markers supported moderately the AF paternity hypothesis (LR = 13.4; W = 93.1%). The application of different mutation models showed a consistent support to the AF paternity hypothesis (PI = 93.1-99.95%), which could be useful for interpretation in these multistep STR mutation cases. In brief, we showed the impact of a four-step mutation at D22S1045 to obtain definitive paternity conclusions, particularly under a complex scenario when the AF-brother hypothesis is assessed. Forensic genomics arises as the next option for similar complex paternity cases.
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Sitios Genéticos , Genotipo , Repeticiones de Microsatélite , Mutación , Paternidad , Adulto , Niño , Femenino , Genética Forense , Humanos , Masculino , MéxicoRESUMEN
OBJECTIVE: To test the acceptability and effectiveness of a disability prevention intervention, Positive Minds-Strong Bodies (PMSB), offered by paraprofessionals to mostly immigrant elders in four languages. DESIGN: Randomized trial of 307 participants, equally randomized into intervention or enhanced usual care. SETTING: Community-based organizations in Massachusetts, New York, Florida, and Puerto Rico serving minority elders. Data collected at baseline, 2, 6, and 12 months, between May 2015 and March 2019. PARTICIPANTS: English-, Spanish-, Mandarin-, or Cantonese-speaking adults, age 60+, not seeking disability prevention services, but eligible per elevated mood symptoms and minor to moderate physical dysfunction. INTERVENTIONS: Ten individual sessions of cognitive behavioral therapy (PM) concurrently offered with 36 group sessions of strengthening exercise training (SB) over 6 months compared to enhanced usual care. MEASUREMENTS: Acceptability defined as satisfaction and attendance to >50% of sessions. Effectiveness determined by changes in mood symptoms (HSCL-25 and GAD-7), functional performance (SPPB), self-reported disability (LLFDI), and disability days (WHODAS 2.0). RESULTS: Around 77.6% of intervention participants attended over half of PM Sessions; 53.4% attended over half of SB sessions. Intent-to-treat analyses at 6 months showed significant intervention effects: improved functioning per SPPB and LLFDI, and lowered mood symptoms per HSCL-25. Intent-to-treat analyses at 12 months showed that effects remained significant for LLFDI and HSCL-25, and disability days (per WHODAS 2.0) significantly decreased 6-month after the intervention. CONCLUSIONS: PMSB offered by paraprofessionals in community-based organizations demonstrates good acceptability and seems to improve functioning, with a compliance-benefit effect showing compliance as an important determinant of the intervention response.
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Actividades Cotidianas , Terapia Cognitivo-Conductual , Emigrantes e Inmigrantes , Ejercicio Físico , Salud Mental , Grupos Minoritarios , Aceptación de la Atención de Salud , Rendimiento Físico Funcional , Negro o Afroamericano , Anciano , Asiático , Agentes Comunitarios de Salud , Evaluación de la Discapacidad , Estudios de Factibilidad , Femenino , Estado de Salud , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Cuestionario de Salud del Paciente , Satisfacción del Paciente , Medicina Preventiva , Población BlancaRESUMEN
OBJECTIVES: Genetic variation of the fat mass and obesity associated gene (FTO) has been identified as a risk factor for obesity and obesity traits. Distribution of FTO single nutleotide polymorphisms (SNPs) rs1421085T>C, rs9939609T>A, rs8057044G>A and copy number variation (CNV) was evaluated in association with childhood obesity or overweight status in children with Mayan ethnicity. METHODS: We included 318 school-aged children with obesity or overweight status (body mass index [BMI]: >85th percentile) and 303 children with normal weight (BMI: 15th-85th percentile). Genotyping was performed using real-time polymerase chain reaction (RT-PCR) with TaqMan probes. The cross-sectional study was carried out using univariate and multivariate logistic regression models adjusted for gender. RESULTS: FTO-SNP rs1421085 showed significant differences between children with obesity and children with normal weight for the heterozygous genotype (P = 0.003) and for allele frequencies (P = 0.023). Adjusting by gender, significant differences were found in frequencies of the hetezygous genotype of SNPs rs9939609 (P = 0.023) and rs1421085 (P = 0.003) as well as in allele frequencies (P = 0.042 and P = 0.013, respectively) between girls with obesity and girls without obesity. In contrast, SNP rs8057044 was significantly different only between heterozygous overweight versus normal weight boys (P = 0.035) and for the allele frequency of rs8057044 (P = 0.021). The mean relative CNV was significantly higher in male overweight children than in boys with normal weight (P = 0.000). CONCLUSIONS: The FTO SNP rs1421085 is a genetic factor associated with obesity in Mayan school-aged children. FTO SNPs rs1421085 and rs9939609 affect genetic susceptibility for obesity only in girls, whereas, SNP rs8057044 and CNV are associated with overweight status only in boys.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Peso Corporal/genética , Variación Genética , Sobrepeso/epidemiología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Indígenas Norteamericanos/estadística & datos numéricos , Masculino , México/epidemiología , Sobrepeso/genética , Obesidad Infantil/epidemiología , Obesidad Infantil/genética , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism.
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Cromosomas Humanos Par 2/genética , Fracturas Osteoporóticas/genética , Fracturas de la Columna Vertebral/genética , Anciano , Anciano de 80 o más Años , Densidad Ósea/genética , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Posmenopausia , Sitios de Carácter CuantitativoRESUMEN
CONTEXT: Latino immigrants constitute a large portion of the Spanish and US immigrant populations, yet a dearth of research exists regarding barriers to retention in behavioral health care. OBJECTIVES: To identify and compare perceived barriers related to behavioral health care among first- and second-generation Latinos in Boston, Madrid, and Barcelona, and evaluate whether the frequency of behavioral health care use in the last year was related to these barriers. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the International Latino Research Partnership project. First- or second-generation self-identified Latino immigrants aged 18 years and more who resided more than 1 year in the host country were recruited from community agencies and primary care, mental health, substance abuse, and HIV clinics. MAIN OUTCOME MEASURES: Eleven barriers were assessed and compared across sites. The relationship between barriers and behavioral services visits within the last year was evaluated, adjusting for sociodemographics, clinical measures, degree of health literacy, cultural, and social factors. RESULTS: Wanting to handle the problem on one's own, thinking that treatment would not work, and being unsure of where to go or who to see were the most frequently reported barriers for Latino immigrants. Previous treatment failure, difficulties in transportation or scheduling, and linguistic barriers were more likely to be reported in Boston; trying to deal with mental health problems on one's own was more commonly reported in Barcelona and Madrid. Two barriers associated with the number of visits were concerns about the cost of services and uncertainty about where to go or who to see. CONCLUSIONS: After adjusting for sociodemographics, clinical measures, degree of health literacy, cultural, and social factors, barriers still differed significantly across sites. Efforts to improve behavioral health services must be tailored to immigrants' context, with attention to changing attitudes of self-reliance and outreach to improve access to and retention in care.
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Actitud Frente a la Salud , Terapia Conductista , Emigrantes e Inmigrantes/psicología , Hispánicos o Latinos/psicología , Trastornos Relacionados con Sustancias/terapia , Cumplimiento y Adherencia al Tratamiento/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , España , Estados Unidos , Adulto JovenRESUMEN
Genome-wide association studies (GWAS) have been successful in identifying loci associated with a wide range of complex human traits and diseases. Up to now, the majority of GWAS have focused on European populations. However, the inclusion of other ethnic groups as well as admixed populations in GWAS studies is rapidly rising following the pressing need to extrapolate findings to non-European populations and to increase statistical power. In this paper, we describe the methodological steps surrounding genetic data generation, quality control, study design and analytical procedures needed to run GWAS in the multiethnic and highly admixed Generation R Study, a large prospective birth cohort in Rotterdam, the Netherlands. Furthermore, we highlight a number of practical considerations and alternatives pertinent to the quality control and analysis of admixed GWAS data.
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Enfermedad/genética , Estudio de Asociación del Genoma Completo , Población Blanca/genética , Etnicidad , Ligamiento Genético , Genotipo , Humanos , Modelos Logísticos , Países Bajos , Fenotipo , Vigilancia de la Población , Estudios ProspectivosRESUMEN
To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11) observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located ± 500 kb from rs917727 in 11,052 additional individuals from five independent studies including children and adults, together with de novo genotyping of rs3801387 (in perfect linkage disequilibrium (LD) with rs917727) in 1,014 mothers of children from the discovery cohort. The top signal mapping in the surroundings of WNT16 was replicated across studies with a meta-analysis P = 2.6 × 10(-31) and an effect size explaining between 0.6%-1.8% of TB-BMD variance. Conditional analyses on this signal revealed a secondary signal for total body BMD (P = 1.42 × 10(-10)) for rs4609139 and mapping to C7orf58. We also examined the genomic region for association with skull BMD to test if the associations were independent of skeletal loading. We identified two signals influencing skull BMD variation, including rs917727 (P = 1.9 × 10(-16)) and rs7801723 (P = 8.9 × 10(-28)), also mapping to C7orf58 (r(2) = 0.50 with rs4609139). Wnt16 knockout (KO) mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level. In summary, we detected two independent signals influencing total body and skull BMD variation in children and adults, thus demonstrating the presence of allelic heterogeneity at the WNT16 locus. One of the skull BMD signals mapping to C7orf58 is mostly driven by children, suggesting temporal determination on peak bone mass acquisition. Our life-course approach postulates that these genetic effects influencing peak bone mass accrual may impact the risk of osteoporosis later in life.
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Alelos , Densidad Ósea/genética , Estudio de Asociación del Genoma Completo , Osteoporosis/genética , Proteínas Wnt/genética , Adulto , Factores de Edad , Animales , Densidad Ósea/fisiología , Niño , Preescolar , Femenino , Perfilación de la Expresión Génica , Frecuencia de los Genes , Heterogeneidad Genética , Humanos , Masculino , Ratones , Fenotipo , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Cráneo/fisiologíaRESUMEN
BACKGROUND: Osteoporosis is characterized by low bone mineral density (BMD), which is determined by an interaction of genetic, metabolic and environmental factors. AIM: To analyse the association between two polymorphisms of VDR as well as their haplotypes with BMD in post-menopausal Maya-Mestizo women. SUBJECTS AND METHODS: This study comprised 600 post-menopausal Maya-Mestizo women. A structured questionnaire for risk factors was applied and BMD was assessed at the lumbar spine (LS) and total hip (TH) by dual-energy X-ray absorptiometry. DNA was extracted from blood leukocytes. Two single-nucleotide polymorphisms of VDR (rs731236 and rs2228570) were studied using real-time PCR allelic discrimination for genotyping. Differences between the means of the BMDs according to the genotype were analysed with covariance. Haplotype analysis was conducted. RESULTS: TT genotype of rs731236 of VDR had higher BMD at total hip and femoral neck (FN), and one haplotype formed by the two polymorphisms was associated with only TH-BMD variations. This difference was statistically significant after adjustment for confounders. The genotype of rs2228570 of VDR analysis showed no significant differences with BMD variations. CONCLUSION: The results showed that the TT genotype of rs731236 of VDR and one haplotype formed by rs731236 and rs2228570 polymorphisms were associated with higher BMD at TH and FN.
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Densidad Ósea/genética , Cuello Femoral/fisiología , Cadera/fisiología , Vértebras Lumbares/fisiología , Osteoporosis Posmenopáusica/genética , Receptores de Calcitriol/genética , Absorciometría de Fotón , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , México/epidemiología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Encuestas y CuestionariosRESUMEN
Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.
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Encefalopatías Metabólicas Innatas , Carnitina , Temblor , Humanos , Femenino , Adolescente , Mutación/genética , Vitaminas , Oxidorreductasas de Alcohol/genéticaRESUMEN
Introduction: Genetic variants that control dopamine have been associated with obesity in children through loss of control of satiety and impulses, the manifestation of addictive eating behaviors, and specific personality traits. The variants include FTO-rs9939609 and the MAO-A 30 pb u-VNTR low-transcription alleles (LTA). Objective: To evaluate the genetic association of FTO-rs9939609 and the MAO-A LTA, along with personality traits and eating behavior with obesity in Mayan children from Mexico. Methods: We cross-sectionally evaluated 186 children (70 with obesity and 116 with normal weight) 6-12 years old from Yucatan, Mexico. Nutritional status was defined with body mass index (BMI) percentiles. Personality traits were evaluated with the Conners and TMCQ tests; eating behavior was evaluated with the CEBQ test. Genotyping with real-time PCR and TaqMan probes was used for FTO-rs9939609, whereas PCR amplification was used for MAO-A u-VNTR. Results: High-intensity pleasure (p = 0.013) and moderate appetite (p = 0.032) differed according to nutritional status. Heterozygous FTO-rs9939609 T/A children showed higher mean scores of low-intensity pleasure (p = 0.002) and moderate appetite (p = 0.027) than homozygous T/T. Hemizygous boys having MAO-A LTA showed significantly higher mean scores of anxiety (p = 0.001) and impulsivity (p = 0.008). In multivariate models, only LTA alleles of MAO-A explained obesity in boys (OR = 4.44; 95% CI = 1.18-16.63). Conclusion: In the present study, MAO-A u-VNTR alleles were associated with obesity in multivariate models only in boys. These alleles might also have a role in personality traits such as anxiety and impulsivity, which secondly contribute to developing obesity in Mayan boys.
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Introduction: IFN-α is the main cytokine in SLE, and single nucleotide polymorphisms (SNP) in different genes could induce it. Aim: To determine the association of rs2004640 (IRF5), rs179008 (TLR7), rs1800795 (IL-6) and rs2280788 (CCL5) with SLE in Mexican women with Mayan ethnicity. Methods: DNA and RNA were isolated from the peripheral blood of 110 patients and 200 healthy control subjects. SNP genotyping and gene expression analysis of IRF5, TLR7, IL-6 and IFN-α were determined by real-time PCR and analyzed with SNP Stat, Stata 10.1 and Graph Pad Prism v5. Results: rs2004640, rs179008, and rs1800795 in both groups were according to Hardy-Weinberg equilibrium. Risk alleles rs179008T and rs2004640T frequencies were higher in controls (p = 0.015 and p = 0.028, respectively), whereas rs179008A frequency was higher in patients (p = 0.015). Allelic combination AGT frequency was higher in patients (p = 0.001). IL-6 rs1800795C > G and CCL5 rs2280788G > C frequencies did not show significant differences (p > 0.05), being rs2280788G (CCL5) monomorphic in controls. SLE patients showed higher TLR7, IRF5, IL6, and IFN-α mRNA levels. IRF5 expression was higher in SLE patients homozygous for rs2004640T (IRF5). Conclusion: This work showed the contribution of TLR7 and IRF5 in SLE pathogenesis in Mayan females from Yucatan.
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OBJECTIVE: Osteoporosis is a complex disease characterized principally by low bone mineral density (BMD), which is determined by an interaction of genetic, metabolic, and environmental factors. The aim of this study was to analyze the possible association among one polymorphism of LRP5 and three polymorphisms of TNFRSF11B as well as their haplotypes with BMD variations in Maya-Mestizo postmenopausal women. METHODS: We studied 583 postmenopausal women of Maya-Mestizo ethnic origin. A structured questionnaire for risk factors was applied and BMD was measured in lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. One single-nucleotide polymorphism of LRP5 (rs3736228, p.A1330V) and three of TNFRSF11B (rs4355801, rs2073618, and rs6993813) were studied using real-time PCR allelic discrimination for genotyping. Differences between the means of the BMDs according to the genotype were analyzed with covariance. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis of TNFRSF11B was conducted. RESULTS: The Val genotype of the rs3736228 (p.A1330V) of LRP5 was significantly associated with BMD variations at the LS, TH, and FN. None of the three polymorphisms of TNFRSF11B was associated with BMD variations. CONCLUSIONS: Our results show that p.A1330V was significantly associated with BMD variations at all three skeletal sites analyzed; the Val allele and the Val/Val genotype were those most frequently found in our population.
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Densidad Ósea , Enfermedades Óseas Metabólicas/genética , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Osteoprotegerina/genética , Polimorfismo de Nucleótido Simple , Posmenopausia , Absorciometría de Fotón , Anciano , Alelos , Enfermedades Óseas Metabólicas/epidemiología , Femenino , Fémur/fisiología , Haplotipos , Humanos , Indígenas Norteamericanos , Desequilibrio de Ligamiento , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/sangre , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Vértebras Lumbares/fisiología , México/epidemiología , Persona de Mediana Edad , Osteoporosis/epidemiología , Osteoporosis/genética , Osteoprotegerina/sangre , Osteoprotegerina/metabolismo , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Encuestas y CuestionariosRESUMEN
Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.
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Genotipo , Lupus Eritematoso Sistémico/genética , Receptor Toll-Like 7/genética , Adulto , Alelos , Variaciones en el Número de Copia de ADN , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , México , Polimorfismo de Nucleótido Simple , Población BlancaRESUMEN
BACKGROUND: Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. METHODS: The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. RESULTS: Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p < 0.05). The heterozygous CT genotype of -108CT polymorphism, the RR genotype of Q192R polymorphism, both LM and MM genotypes of L55M polymorphism, and the haplotypes 221 and 222 (for -108CT, L55M, and Q192R) were associated with the risk for having a child affected by SB (p < 0.02). The heterozygous -108CT genotype was associated only maternally, whereas the heterozygous L55M genotype was relevant only in the fathers. The RR homozygous genotype was relevant both in mothers and fathers, suggesting the importance of this substrate-specific polymorphism. CONCLUSION: Results suggest that PON1 polymorphisms are relevant risk factors for having offspring affected with SB in this population from Southeast Mexico.
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Arildialquilfosfatasa/genética , Polimorfismo Genético/genética , Disrafia Espinal/genética , Adolescente , Adulto , Arildialquilfosfatasa/metabolismo , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Heterocigoto , Homocigoto , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Organofosfatos/toxicidad , Plaguicidas/toxicidad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Disrafia Espinal/epidemiología , Adulto JovenRESUMEN
Latinos are underrepresented in clinical trials, where they encounter challenges in participation and a lack of effective recruitment and retention strategies. For Latino migrants with mental health and substance use problems, these challenges are even greater. Analyzing results from a multicenter randomized clinical trial for Latino migrants with mental health and substance use problems in Boston, Massachusetts, USA as well as Madrid and Barcelona, Spain, we describe six retention strategies used to facilitate participant engagement in follow-up assessments, and report the sociodemographic, clinical, and educational factors associated with research assessment completion. Among 341 randomized participants, 77% completed the 12-month follow-up and 75% completed at least 3 of the 4 follow-up assessments. Having a high school diploma, being recruited at community centers versus other sites, and having a less severe mental health condition were significantly associated with completing more follow-up interviews. Rigorous and customized methods reflecting participant's individual context can bolster research assessment completion for diverse Latino populations with behavioral health concerns.
Asunto(s)
Hispánicos o Latinos , Trastornos Relacionados con Sustancias , Humanos , Massachusetts , Salud Mental , EspañaRESUMEN
Importance: Immigrants are at an increased risk for co-occurring mental health and substance misuse symptoms; however, effective treatments are lacking. Objective: To evaluate the effectiveness of the Integrated Intervention for Dual Problems and Early Action (IIDEA) program compared with enhanced usual care. Design, Setting, and Participants: This effectiveness randomized clinical trial was conducted from September 2, 2014, to February 2, 2017, in 17 clinics or emergency departments and 24 community sites in Boston, Massachusetts, as well as in Madrid and Barcelona, Spain. Equal randomization (1:1) in 2-person blocks was used, assigning participants to either the IIDEA treatment group (n = 172) or the enhanced usual care control group (n = 169). Intent-to-treat analyses assessed effectiveness, and post hoc analyses examined whether results varied by symptom severity or treatment dose. Eligible participants were between 18 and 70 years of age, self-identified as Latino, screened positive for co-occurring symptoms, and were not receiving specialty behavioral health services. Interventions: Participants were randomized to a 10-session IIDEA treatment or to enhanced usual care. Main Outcomes and Measures: Primary outcomes were changes in alcohol and drug misuse and results of a urine test for drug metabolites but not for alcohol misuse. Secondary outcomes were symptoms of depression, generalized anxiety, posttraumatic stress disorder, and overall mental health. Results: In total, 341 participants were randomized to either the IIDEA treatment group (n = 172; 94 [54.7%] female, mean [SD] age, 33.5 [11.6] years) or the enhanced usual care control group (n = 169; 80 [47.3%] female, mean [SD] age, 34.3 [11.8] years). No statistically significant effects of IIDEA were found for primary drug and alcohol outcomes (ASI Lite-drug score: ß = -0.02 [SE, 0.69; P = .88; Cohen d, 0.00; 95% CI, -0.17 to 0.17]; ASI Lite-alcohol score: ß = -0.01 [SE, 1.19; P = .66; Cohen d, 0.00; 95% CI, -0.12 to 0.12]; urine drug test result: ß = -0.36 [SE, 0.43; P = .50; OR, 0.70; 95% CI, 0.30-1.61]), but statistically significant effects were observed for secondary mental health outcomes. The IIDEA treatment was effective in reducing depressive symptoms per the Public Health Questionnaire-9 score (ß = -1.14; SE, 0.47; P = .02; Cohen d, 0.20 [95% CI, 0.04-0.36]), posttraumatic stress disorder symptoms per the Posttraumatic Stress Disorder Checklist-5 score (ß = -3.23; SE, 1.59; P = .04; Cohen d, 0.25 [95% CI, 0.01-0.37]), and overall mental health symptoms per the Hopkins Symptom Checklist-20 (ß = -0.20; SE, 0.07; P = .01; Cohen d, 0.25 [95% CI, 0.08-0.42]) and composite mental health (ß = -3.70; SE, 1.75; P = .04; Cohen d, 0.19 [95% CI, 0.01-0.36]) scores at the 6-month follow-up. Exploratory analyses suggested that 6-month treatment effects occurred for patients whose drug misuse was moderate to severe at the baseline assessment. Among patients with moderate to severe substance misuse, IIDEA substantially reduced substance use per the urine test results (odds ratio, 0.25 [95% CI, 0.09-0.67]; P = .01). Treatment dose showed small to large effect sizes by outcome. Conclusions and Relevance: The IIDEA treatment did not change drug misuse but did improve secondary mental health and substance misuse outcomes for a heterogeneous population with moderate to severe symptoms; this finding provides a path for treating Latino immigrants with co-occurring mental health and substance misuse symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02038855.
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Consumo de Bebidas Alcohólicas , Trastornos Mentales , Atención Plena/métodos , Trastornos Relacionados con Sustancias , Adulto , Consumo de Bebidas Alcohólicas/psicología , Consumo de Bebidas Alcohólicas/terapia , Diagnóstico Dual (Psiquiatría)/psicología , Diagnóstico Dual (Psiquiatría)/estadística & datos numéricos , Emigrantes e Inmigrantes , Femenino , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/etnología , Trastornos Mentales/psicología , Trastornos Mentales/terapia , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Escalas de Valoración Psiquiátrica , Detección de Abuso de Sustancias/métodos , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/psicología , Trastornos Relacionados con Sustancias/terapiaRESUMEN
We examined cultural differences in the item characteristic functions of self-reported of symptoms of depression, anxiety, and mania-hypomania in a Latino population taking Computerized Adaptive Tests for Mental Health (CAT-MH) in Spanish versus a non-Latino sample taking the tests in English. We studied differential item functioning (DIF) of the most common adaptively administered symptom items out of a bank of 1,008 items between Latino (n = 1276) and non-Latino (n = 798) subjects. For depression, we identified 4 items with DIF that were good discriminators for non-Latinos but poor discriminators for Latinos. These items were related to cheerfulness, life satisfaction, concentration, and fatigue. The correlation between the original calibration and a Latino-only new calibration after eliminating these items was r = .990. For anxiety, no items with DIF were identified. The correlation between the original and new calibrations was r = .993. For mania-hypomania, we identified 4 items with differential item functioning that were good discriminators for non-Latinos but poor discriminators for Latinos. These items were related to risk-taking, self-assurance, and sexual activity. The correlation between the original and new calibration was r = .962. Once the identified items were removed, the correlation between the original calibration and a Latino-only calibration was r = .96 or greater. These findings reveal that the CAT-MH can be reliably used to measure depression, anxiety, and mania in Latinos taking these tests in Spanish. (PsycINFO Database Record (c) 2018 APA, all rights reserved).