Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Dev Psychobiol ; 65(4): e22388, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37073588

RESUMO

Previous work has shown that children's shyness is related to personal anxiety during social stress, but we know little about how shyness is related to anxiety during a peer's social stress. Children (Mage  = 10.22 years, SD = 0.81, N = 62) were paired with an unfamiliar peer and engaged in a speech task while electrocardiography was recorded. We modeled changes in children's heart rate, a physiological correlate of anxiety, while they observed their peer prepare and deliver a speech. Results revealed that the observing child's shyness related to increases in their heart rate during their peer's preparation period, but modulation of this arousal was sensitive to the presenting peer's anxious behavior while delivering their speech. Specifically, if the presenting child displayed high levels of anxious behavior, the observing child's shyness was related to further increases in heart rate, but if the presenting child displayed low levels of anxious behavior, the observing child's shyness was related to decreases in heart rate from the preparation period. Shy children may experience physiological arousal to a peer's social stress but can regulate this arousal based on social cues from the peer, which may be due to heightened social threat detection and/or empathic anxiety.


Assuntos
Ansiedade , Timidez , Humanos , Criança , Empatia , Frequência Cardíaca/fisiologia , Nível de Alerta
2.
Emotion ; 23(4): 949-960, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36048036

RESUMO

The way children express and respond to emotions when they first meet is crucial to friendship initiation. But for highly shy children, these exchanges are particularly challenging. Existing research is based on individual and total frequency measures of emotion that do not reflect the transactional and dynamic nature of emotions in real-life peer interactions. We examined how shyness and dyadic similarity in shyness influence children's moment-to-moment dyadic emotion sequences with a new peer. Thirty age- and gender-matched dyads (Mage = 10.13 years, 75.8% White) were observed during an unstructured "getting to know you" task. Children's shyness was assessed through parent- and child-report. Using grid-sequence analysis (Brinberg et al., 2017) we identified three dyadic emotion clusters: Flexible and Shared Positive Affect (60%), Flexible and Shared Neutral Affect (35%), and Stable and Shared Negative Affect (17%). Children in the Stable and Shared Negative Affect cluster were rated higher in shyness relative to children in the Flexible and Shared Positive Affect cluster. Further, children more similar in shyness to their dyadic partner displayed more stable negative and neutral affect expressions than children who differed in shyness from their partner. Together, these findings suggest that shyness is related to less positive and less flexible emotion expressions when meeting a new peer, holding critical implications for friendship initiation among children varying in shyness. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Emoções , Timidez , Humanos , Criança , Grupo Associado , Amigos , Comportamento Infantil/psicologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-36350479

RESUMO

This study identified typologies of specific non-suicidal self-injury (NSSI) functions among youth admitted for psychiatric hospitalization and investigated clinically relevant correlates. Inpatient youth (n = 68) aged 10-17 years reported on their reasons to engage in NSSI, frequency and severity of NSSI, and symptoms of borderline personality disorder (BPD). A latent class analysis using youth's specific NSSI functions as indicators found two NSSI function typologies, which were differentially associated with clinical correlates. The Multiple Functions class (n = 28) endorsed to "feel something," "punish self," "escape feelings," "relieve anxiety," "stop feeling self-hatred," "stop feeling angry," "show much they are hurting," and "create a hurt that can be soothed." Conversely, the Single/Avoidant Function class (n = 40) endorsed one primary function-i.e., to "escape feelings." Youth in the Multiple Functions class reported significantly more frequent self-injury and greater BPD symptomology. The present study illustrates the importance of examining constellations of specific NSSI functions in inpatient care settings, given their unique associations with NSSI frequency and features of BPD. These findings could inform targeted psychological screening and, in turn, guide the implementation of interventions for elevated NSSI frequency and BPD symptomology among inpatient youth, based on NSSI functions endorsed.

4.
J Exp Child Psychol ; 213: 105257, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34425400

RESUMO

Mind wandering is a ubiquitous experience during adulthood and has received significant scholarly attention in recent years. Relatively few studies, however, have examined the phenomenon in children. Building on recent work, the current study examined the frequency and validity of children's reports of mind wandering while completing a minimalistic task previously unused in past child research-the Metronome Response Task (MRT) [Journal of Experimental Psychology: Human Perception and Performance (2013), Vol. 39, pp. 1-5]. Furthermore, the current study examined how parent reports of executive dysfunction in daily life relate to children's reports of mind wandering and behavioral performance in the MRT. A total of 81 children aged 7-9 years completed the MRT, the demands of which simply involved pressing a key on a computer keyboard in concert with the unwavering tones of a metronome. Sporadic experience-sampling probes gauged whether children were on-task or mind wandering. Parents also reported on their children's day-to-day difficulties with executive functioning across several domains. A series of multilevel models revealed that children reported being on-task more frequently then mind wandering and that children were more variable and less synchronous in their keypresses preceding reports of mind wandering than preceding reports of being on task. In addition, parent-reported difficulties with behavioral regulation predicted higher rates of mind wandering, whereas both behavioral dysregulation and metacognitive difficulties predicted lower MRT performance. These findings suggest that children are able to reliably report on their experiences of mind wandering in boredom-inducing contexts and advance our understanding of the factors underlying children's experience of mind wandering under real-world conditions.


Assuntos
Atenção , Metacognição , Adulto , Criança , Função Executiva , Humanos , Análise e Desempenho de Tarefas
5.
Genome Med ; 13(1): 123, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340684

RESUMO

BACKGROUND: Obesity predisposes individuals to multiple cardiometabolic disorders, including type 2 diabetes (T2D). As body mass index (BMI) cannot reliably differentiate fat from lean mass, the metabolically detrimental abdominal obesity has been estimated using waist-hip ratio (WHR). Waist-hip ratio adjusted for body mass index (WHRadjBMI) in turn is a well-established sex-specific marker for abdominal fat and adiposity, and a predictor of adverse metabolic outcomes, such as T2D. However, the underlying genes and regulatory mechanisms orchestrating the sex differences in obesity and body fat distribution in humans are not well understood. METHODS: We searched for genetic master regulators of WHRadjBMI by employing integrative genomics approaches on human subcutaneous adipose RNA sequencing (RNA-seq) data (n ~ 1400) and WHRadjBMI GWAS data (n ~ 700,000) from the WHRadjBMI GWAS cohorts and the UK Biobank (UKB), using co-expression network, transcriptome-wide association study (TWAS), and polygenic risk score (PRS) approaches. Finally, we functionally verified our genomic results using gene knockdown experiments in a human primary cell type that is critical for adipose tissue function. RESULTS: Here, we identified an adipose gene co-expression network that contains 35 obesity GWAS genes and explains a significant amount of polygenic risk for abdominal obesity and T2D in the UKB (n = 392,551) in a sex-dependent way. We showed that this network is preserved in the adipose tissue data from the Finnish Kuopio Obesity Study and Mexican Obesity Study. The network is controlled by a novel adipose master transcription factor (TF), TBX15, a WHRadjBMI GWAS gene that regulates the network in trans. Knockdown of TBX15 in human primary preadipocytes resulted in changes in expression of 130 network genes, including the key adipose TFs, PPARG and KLF15, which were significantly impacted (FDR < 0.05), thus functionally verifying the trans regulatory effect of TBX15 on the WHRadjBMI co-expression network. CONCLUSIONS: Our study discovers a novel key function for the TBX15 TF in trans regulating an adipose co-expression network of 347 adipose, mitochondrial, and metabolically important genes, including PPARG, KLF15, PPARA, ADIPOQ, and 35 obesity GWAS genes. Thus, based on our converging genomic, transcriptional, and functional evidence, we interpret the role of TBX15 to be a main transcriptional regulator in the adipose tissue and discover its importance in human abdominal obesity.


Assuntos
Tecido Adiposo/metabolismo , Regulação da Expressão Gênica , Obesidade Abdominal/genética , Obesidade Abdominal/metabolismo , Proteínas com Domínio T/metabolismo , Transativadores/metabolismo , Adipócitos , Adiposidade/genética , Idoso , Algoritmos , Biomarcadores , Índice de Massa Corporal , Células Cultivadas , Biologia Computacional/métodos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Relação Cintura-Quadril
7.
J Adolesc ; 92: 46-56, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34425508

RESUMO

INTRODUCTION: In recent decades, adolescents' interactions with peers have increasingly transitioned online. While socially interactive technologies provide multiple avenues for positive communication between peers, adolescents may experience harmful online peer interactions, with such interactions negatively impacting their well-being. A paucity of work exists investigating how adolescents' characteristics are related to their communicative choices on social media and if such choices can be influenced by cues to consider a recipient. Addressing this gap, this work examines experimental manipulations of perspective-taking and individual differences in socio-cognitive skills as they relate to adolescents' communicative choices online. METHOD: Within individual sessions, 12- to 15-year-old Canadian participants (N = 72, 36 girls) viewed pictures of other adolescents on a simulated social media app similar to Snapchat and chose between pre-written aggressive or prosocial comments to send to a recipient under three conditions: a perspective-taking cue, a time-delay, no delay. Participants also completed self-report questionnaires assessing emotion regulation and empathy. RESULTS: Following perspective-taking cues, participants chose more prosocial comments to send compared to when participants were permitted to choose a comment immediately after viewing another adolescent's picture, while controlling for a brief time-delay. Adolescents' individual characteristics (i.e., Social Media Use, State Mood, Affective Empathy, Gender) were associated with their communicative choices online. CONCLUSIONS: Findings from this work provide new insight into the ways adolescents navigate their complex and increasingly online peer interactions. Further, the results suggest that adolescents' social media communication is malleable with a brief perspective-taking cue to consider a recipient.


Assuntos
Comportamento do Adolescente , Grupo Associado , Adolescente , Canadá , Criança , Comunicação , Empatia , Feminino , Humanos
8.
Br J Clin Psychol ; 60(1): 99-115, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33368387

RESUMO

OBJECTIVE: Although self-compassion facilitates eating disorder symptom remission, individuals with eating disorders are fearful of developing it and higher fears of self-compassion are associated with poorer treatment outcomes. In-depth exploration of individuals' pros and cons of behaviour change is generally helpful at resolving ambivalence; however, no research has examined the pros and cons individuals with eating disorders perceive to be associated with developing self-compassion, limiting our understanding of their personal experiences when confronted with self-compassion. Given the research suggesting higher resistance to self-compassion development in individuals with anorexia nervosa (AN), the present study used qualitative methods to gain a deeper understanding of their perceived pros and cons to self-compassion. METHODS: Thirty-seven women with typical (64%) and atypical (36%) AN signed up for a study on self-help strategies for daily distress. Upon learning that the intervention would entail cultivating self-compassion, they identified their perceived pros and cons of developing self-compassion by typing them out. RESULTS: Thematic analysis was used to extract themes. Three superordinate cons and four superordinate pros of self-compassion emerged. Perceived cons were as follows: self-compassion leading to personal shortcomings; apprehension and doubt about the efficacy of self-compassion; and emotional challenges associated with developing self-compassion. Perceived pros were as follows: improved health; personal development (e.g., growth, coping); improved outlook; and enhanced social relationships. CONCLUSIONS: These findings reveal the various advantages and disadvantages that women with AN perceive to be associated with developing self-compassion. Results may help clinicians work more sensitively and effectively when trying to cultivate self-compassion in patients who have AN. PRACTITIONER POINTS: This research suggests that patients with anorexia nervosa (AN) perceive various disadvantages to cultivating self-compassion, but also certain advantages. By familiarizing themselves with the pros and cons to self-compassion identified by individuals with AN, clinicians may be able to more effectively listen to and communicate with their patients about ambivalence about self-compassion development. Clinicians may want to listen for and explore concerns in their AN patients that self-compassion will lead to personal shortcomings, fail to be beneficial, and be emotionally challenging. Clinicians may want to listen for and help patients elaborate upon their beliefs about how self-compassion might benefit their outlook, health, personal development, and relationships.


Assuntos
Anorexia Nervosa/psicologia , Empatia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Adolescente , Adulto , Anorexia Nervosa/terapia , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Resultado do Tratamento , Adulto Jovem
9.
PLoS Genet ; 16(9): e1009018, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925908

RESUMO

Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin resistance already in non-diabetic individuals, we utilized the UK Biobank and METSIM cohort to perform a Mendelian randomization (MR) analyses in the non-diabetic individuals. Our results suggest that both prediabetes and systemic insulin resistance are caused by obesity (p = 1.2×10-3 and p = 3.1×10-24). As obesity reflects the amount of body fat, we next studied how adipose tissue affects insulin resistance. We performed both bulk RNA-sequencing and single nucleus RNA sequencing on frozen human subcutaneous adipose biopsies to assess adipose cell-type heterogeneity and mitochondrial (MT) gene expression in insulin resistance. We discovered that the adipose MT gene expression and body fat percent are both independently associated with insulin resistance (p≤0.05 for each) when adjusting for the decomposed adipose cell-type proportions. Next, we showed that these 3 factors, adipose MT gene expression, body fat percent, and adipose cell types, explain a substantial amount (44.39%) of variance in insulin resistance and can be used to predict it (p≤2.64×10-5 in 3 independent human cohorts). In summary, we demonstrated that obesity is a strong determinant of both prediabetes and insulin resistance, and discovered that individuals' adipose cell-type composition, adipose MT gene expression, and body fat percent predict their insulin resistance, emphasizing the critical role of adipose tissue in systemic insulin resistance.


Assuntos
Tecido Adiposo/metabolismo , Resistência à Insulina/fisiologia , Obesidade/genética , Adipócitos/metabolismo , Adiposidade , Adulto , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/fisiopatologia , Gordura Subcutânea/metabolismo
10.
Rev. colomb. nefrol. (En línea) ; 6(2): 112-121, jul.-dic. 2019. tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1093035

RESUMO

Resumen Objetivo: establecer la asociación de la insuficiencia renal aguda con los factores demográficos y clínicos en pacientes hospitalizados en la unidad de cuidados intensivos en Colombia. Métodos: estudio analítico de casos y controles cuya fuente de información fue la historia clínica del paciente, en una muestra de 130 casos y 184 controles; pacientes mayores de 18 años, que tenían una tasa de filtración glomerular mayor de 60 ml/min y que cumplían los criterios AKIN mencionar el nombre completo de la sigla. Con la prueba de independencia se estableció el efecto de los factores de interés sobre el desenlace (caso-control), con el Odds Ratio (OR) como medida de asociación con su intervalo de confianza del 95 %. La regresión logística permitió controlar las variables presumibles de confusión. Resultados: la edad promedio de los pacientes fue de 62,2 años (DE=16,7 años), hombres provenientes de la zona urbana y donde la hipertensión sobresalió en el 52,2 % de ellos. Al ingreso, el 55,7 % presentó síndrome coronario y el 40 % desarrolló insuficiencia renal aguda (IRA); el 84,6 % de los pacientes estaba en el estadio I, según la clasificación AKIN. La administración de solución salina al 0,9 % en las primeras 24 horas de ingreso incrementó la oportunidad de IRA 1,8 veces, con respecto a los que se les administró lactato de ringer (OR=1,8 IC (95 % OR: 1,2-2,8), ajustando las demás variables. Conclusión: La administración de lactato ringer disminuyó el desarrollo de la insuficiencia renal aguda. La edad de los pacientes y sus antecedentes posoperatorios, fueron los factores que se relacionaron con la presencia de IRA.


Abstract Objective: To establish the association of acute renal failure with demographic and clinical factors in patients hospitalized in an intensive care unit in a Colombian city. Methods: Analytical case-control study whose source of information was the patient's clinical history, in a sample of 130 cases and 184 controls; the cases were about patients older than 18 years, who had a glomerular filtration rate higher than 60 ml / min and who were able to fulfilled the AKIN criteria. With the independence test, it was established the effect of the factors of interest on the result (case-control), with the Odds Ratio (OR) as a measure of the association with its 95% confidence interval. The logistic regression allowed to control the presumable variables of confusion. Results: The average age of patients was 62.2 years (SD-16.7 years) with a predominance of men from the urban area and where hypertension stood out in 52.2% of them. On admission, 55.7% had coronary syndrome and 40% developed acute renal failure (ARF); 84.6% of the patients were stage according to the AKIN classification. The administration of saline in the first 24 hours of admission increased the possibility of ARF 1.8 times compared to those administered with Ringer's lactate (OR 1.8 CI (95% OR: 1.2-2.8), adjusting for other variables. Conclusion: The administration of ringer's lactate decreases the development of acute renal failure; also, age of the patient and if it came from the postoperative period, were the factors that were related to the presence of kidney disease.


Assuntos
Humanos , Masculino , Feminino , Insuficiência Renal , Unidades de Terapia Intensiva , Nefropatias , Fatores de Risco , Colômbia
11.
Arterioscler Thromb Vasc Biol ; 36(7): 1350-5, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27199446

RESUMO

OBJECTIVE: We recently identified a locus on chromosome 18q11.2 for high serum triglycerides in Mexicans. We hypothesize that the lead genome-wide association study single-nucleotide polymorphism rs9949617, or its linkage disequilibrium proxies, regulates 1 of the 5 genes in the triglyceride-associated region. APPROACH AND RESULTS: We performed a linkage disequilibrium analysis and found 9 additional variants in linkage disequilibrium (r(2)>0.7) with the lead single-nucleotide polymorphism. To select the variants for functional analyses, we annotated the 10 variants using DNase I hypersensitive sites, transcription factor and chromatin states and identified rs17259126 as the lead candidate variant for functional in vitro validation. Using luciferase transcriptional reporter assay in liver HepG2 cells, we found that the G allele exhibits a significantly lower effect on transcription (P<0.05). The electrophoretic mobility shift and ChIPqPCR (chromatin immunoprecipitation coupled with quantitative polymerase chain reaction) assays confirmed that the minor G allele of rs17259126 disrupts an hepatocyte nuclear factor 4 α-binding site. To find the regional candidate gene, we performed a local expression quantitative trait locus analysis and found that rs17259126 and its linkage disequilibrium proxies alter expression of the regional transmembrane protein 241 (TMEM241) gene in 795 adipose RNAs from the Metabolic Syndrome In Men (METSIM) cohort (P=6.11×10(-07)-5.80×10(-04)). These results were replicated in expression profiles of TMEM241 from the Multiple Tissue Human Expression Resource (MuTHER; n=856). CONCLUSIONS: The Mexican genome-wide association study signal for high serum triglycerides on chromosome 18q11.2 harbors a regulatory single-nucleotide polymorphism, rs17259126, which disrupts normal hepatocyte nuclear factor 4 α binding and decreases the expression of the regional TMEM241 gene. Our data suggest that decreased transcript levels of TMEM241 contribute to increased triglyceride levels in Mexicans.


Assuntos
Cromossomos Humanos Par 18 , Fator 4 Nuclear de Hepatócito/genética , Metabolismo dos Lipídeos/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Idoso , Sítios de Ligação , Finlândia , Genes Reporter , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Genótipo , Células Hep G2 , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Desequilíbrio de Ligação , Masculino , Proteínas de Membrana/metabolismo , México , Pessoa de Meia-Idade , Fenótipo , Locos de Características Quantitativas , Transcrição Gênica , Transfecção , Estados Unidos , Regulação para Cima
12.
Carcinogenesis ; 37(6): 547-556, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27207650

RESUMO

Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10(-8) Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10(-6)) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 [95% confidence interval (CI): 1.47-2.36); P = 2.5×10(-7)], 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21-1.55); P = 4.0×10(-7)), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36-2.01); P = 4.1×10(-7)) and 16q12.2 [rs142319636; OR = 1.69 (95% CI: 1.37-2.08); P=7.8×10(-7)]. Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10(-5)) and 11q12.2 (P = 6.8×10(-5)), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Hispânico ou Latino/genética , Idoso , Alelos , Estudos de Coortes , Feminino , Variação Genética , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade
13.
Nat Commun ; 5: 3983, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24886709

RESUMO

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican-Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian-specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans.


Assuntos
Hipercolesterolemia/genética , Hipertrigliceridemia/genética , Indígenas Norte-Americanos/genética , Obesidade/genética , Adulto , Apolipoproteína A-V , Apolipoproteínas A/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 8/genética , Dislipidemias/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Lipase Lipoproteica/genética , Modelos Logísticos , Masculino , México/etnologia , Pessoa de Meia-Idade , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Polimorfismo de Nucleotídeo Único , Proteínas Quinases/genética , População Branca/genética , Adulto Jovem
14.
J Med Genet ; 50(5): 298-308, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23505323

RESUMO

BACKGROUND: The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. METHODS AND FINDINGS: We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.43×10(-08)). Furthermore, three European loci for TGs (APOA5, GCKR and LPL), and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We used cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalised to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. CONCLUSIONS: This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; used the interpopulation heterogeneity to significantly restrict three previously known European GWA signals, and surveyed whether the European lipid GWA SNPs extend to the Mexican population.


Assuntos
Apolipoproteínas A/genética , Loci Gênicos/genética , Hipertrigliceridemia/genética , Hipoalfalipoproteinemias/genética , Indígenas Norte-Americanos/genética , Triglicerídeos/genética , Apolipoproteína A-V , Apolipoproteínas A/sangue , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hipertrigliceridemia/etnologia , Hipoalfalipoproteinemias/etnologia , Desequilíbrio de Ligação , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras , México , Polimorfismo de Nucleotídeo Único/genética , Triglicerídeos/sangue , População Branca/genética
15.
Metabolism ; 62(5): 638-41, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23273975

RESUMO

OBJECTIVE: To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program. Each person with the risk allele (R230C) was matched by age, gender and BMI to three others with the wild type variant (R230R). Following a four week stabilization period, only participants with a greater than 70% adherence to metformin and a stable body weight were prescribed glyburide therapy for a further 16 weeks. The main outcome variable was the glyburide dose required to achieve treatment goals. RESULTS: No significant difference was observed in the glucose lowering effect of glyburide between subjects with the R230C and R230R alleles. However, the dose of sulfonylurea was significantly higher in the R230C participants compared with the R230R subjects (3.3±2.1 vs 6.3±5 mg/day, p<0.001). A higher percentage of R230C participants required at least 5mg of glyburide per day to achieve treatment goals. The glyburide dose was determined by the presence of the risk allele, among other factors. CONCLUSIONS: Patients with type 2 diabetes who have the R230C allele of ABCA1 needed a higher dose of glyburide in order to achieve the same glucose lowering effect as that in persons with the wild type variant.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Resistência a Medicamentos/genética , Glibureto/uso terapêutico , Transportador 1 de Cassete de Ligação de ATP , Adulto , Idoso , Substituição de Aminoácidos , Arginina/genética , Cisteína/genética , Relação Dose-Resposta a Droga , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Glibureto/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/fisiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Método Simples-Cego , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...