RESUMO
AIMS/HYPOTHESIS: We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. METHODS: We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. RESULTS: In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. CONCLUSIONS/INTERPRETATION: We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla/métodos , Adulto , Idoso , Feminino , Genótipo , Hispânico ou Latino/genética , Humanos , Masculino , Americanos Mexicanos/genética , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Texas , Adulto JovemRESUMO
BACKGROUND: Although several lines of evidence suggest that hypomagnesaemia is a risk factor for developing type 2 diabetes, there are no studies regarding the association between hypomagnesaemia and the risk for developing impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Our objective was to examine the association between serum magnesium levels and the risk for developing IFG, IGT and type 2 diabetes. MATERIALS AND METHODS: A total of 1122 individuals (20-65 years of age) were enrolled between 1996 and 1997, and 817 individuals re-examined about 10 years later. New-onset IFG (5.6-7.0 mmol L(-1) fasting glucose), IGT (7.8-11.1 mmol L(-1) glucose 2-h postload), and type 2 diabetes were determined from the number of subjects who had these conditions at the second examination without evidence that they were present at the first one. The relative risk of new-onset metabolic glucose disorders and diabetes (dependent variables) was computed using Poisson regression model adjusted for age, sex, family history of diabetes, waist circumference and homeostasis model assessment for insulin resistance index. Serum magnesium levels of < 0.74 mmol L(-1) (independent variable) defined the exposed group. RESULTS: At baseline, 420 (51.4%) individuals had hypomagnesaemia. New-onset IFG and IGT was identified in 276 (33.8%) individuals. The relative risk for IFG, IGT and IFG + IGT was 1.11 (95% confidence interval, 0.5-5.1), 1.38 (95% confidence interval, 1.1-6.3) and 1.49 (95% confidence interval, 1.1-4.9), respectively. New-onset diabetes was identified in 78 (9.5%) individuals (relative risk 2.54; 95% confidence interval, 1.1-4.1). CONCLUSIONS: Hypomagnesaemia is independently associated with the development of IGT, IFG + IGT and type 2 diabetes, but not with the development of IFG.
Assuntos
Transtornos do Metabolismo de Glucose/etiologia , Deficiência de Magnésio/complicações , Magnésio/análise , Adulto , Idoso , Glicemia/análise , Colorimetria , Diabetes Mellitus Tipo 2/etiologia , Feminino , Seguimentos , Intolerância à Glucose , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
A family-based study has recently reported that a variant located in intron 10 of the gene MGEA5 increases susceptibility to Type 2 Diabetes (T2D). We evaluated the distribution of this SNP in a sample of T2D patients (N = 271) and controls (N = 244) from Mexico City. The frequency of the T allele was higher in the cases (2.6%) than in the controls (1.8%). After adjusting for age, sex, BMI, education, and individual ancestry the odds ratio was 1.60 but the 95% confidence interval was wide and overlapped 1 (0.52-4.86, P-value : 0.404). In order to characterize the distribution of the MGEA5-14 polymorphism in the relevant parental populations, we genotyped this variant in European (and European Americans), West African, and Native American samples. The T-allele was present at a frequency of 2.3% in Spain, 4.2% in European Americans, and 13% in Western Africans, but was absent in two Native American samples from Mexico and Peru. Given the low frequency of the T-allele, further studies using large sample sizes will be required to confirm the role of this variant in T2D.
Assuntos
Antígenos de Neoplasias/genética , Diabetes Mellitus Tipo 2/genética , Histona Acetiltransferases/genética , Indígenas Norte-Americanos/genética , Polimorfismo de Nucleotídeo Único/genética , beta-N-Acetil-Hexosaminidases/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Hialuronoglucosaminidase , Indígenas Sul-Americanos , Masculino , México , EspanhaRESUMO
Polymorphisms within the transcription factor 7-like 2 gene (TCF7L2) have been associated with type 2 diabetes (T2D) in several recent studies. We characterized three of these polymorphisms (rs12255372, rs7903146 and the microsatellite DG10S478) in an admixed sample of 286 patients with T2D and 275 controls from Mexico City. We also analyzed three samples representative of the relevant parental populations: Native Americans from the state of Guerrero (Mexico), Spanish from Valencia and Nigerians (Bini from the Edo region). In order to minimize potential confounding because of the presence of population stratification in the sample, we evaluated the association of the three TCF7L2 polymorphisms with T2D by using the program admixmap to fit a logistic regression model incorporating individual ancestry, sex, age, body mass index and education. The markers rs12255372, rs7903146 and DG10S478 are in tight disequilibrium in the Mexican sample. We observed a significant association between the single-nucleotide polymorphism (SNP) rs12255372 and the microsatellite DG10S478 with T2D in the Mexican sample [rs12255372, odds ratio (OR) = 1.78, p = 0.017; DG10S478, OR = 1.62, p = 0.041]. The SNP rs7903146 shows similar trends, but its association with T2D is not as strong (OR = 1.39, p = 0.152). Analysis of the parental samples, as well as other available data, indicates that there are substantial population frequency differences for these polymorphisms: The frequencies of the T2D risk factors are more than 20% higher in European and West African populations than in East Asian and Native American populations.
Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético , Fatores de Transcrição TCF/genética , Adulto , Alelos , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA/genética , Feminino , Frequência do Gene , Humanos , Indígenas Norte-Americanos/genética , Modelos Logísticos , Masculino , México , Repetições de Microssatélites , Pessoa de Meia-Idade , Modelos Genéticos , Nigéria/etnologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Espanha/etnologia , Proteína 2 Semelhante ao Fator 7 de TranscriçãoRESUMO
BACKGROUND: When a CT scan is not available, an early accurate clinical diagnosis of ischemic stroke is essential to initiate prompt therapy. Our objective was to construct a clinical index that is easy to use when stroke patients are first evaluated at the hospital, to identify those who probably are experiencing an acute ischemic episode. The study was conducted at a university-affiliated medical referral center and two community general hospitals in Mexico. METHODS: Clinical records were reviewed for 801 patients with sudden onset of a focal or global neurologic dysfunction, presumably of vascular origin lasting more than 24 h. Eligibility criteria for this study were admission to the hospital within the first 24 h after symptomatic onset, CT scan diagnosis between 24 and 72 h, and age >45 years. Ischemic stroke included cases of arterial brain infarction, while nonischemic stroke included subarachnoid or intraparenchymatous hemorrhage, mass lesion, venous infarction, and in cases without a CT scan evidence that could explain the clinical manifestations. Data excerpted for analysis were age, sex, history of diabetes mellitus or previous stroke/transient ischemic attack (TIA), time of onset of symptoms, presence of headache, vomiting, neck stiffness, hemiplegia, leukocytosis or atrial fibrillation, diastolic blood pressure, and Glasgow coma scale (GCS) rating. Two multivariable analyses were used: 1) step-wise multiple logistic regression (SMLR), and 2) conjunctive consolidation (CC). RESULTS: After appropriate exclusions, the study proceeded with 83 ischemic and 42 nonischemic stroke patients. With SMLR, six variables were selected as predictive for ischemic stroke, including neck stiffness, diastolic blood pressure, previous history of stroke/TIA, hemiplegia, GCS, and atrial fibrillation. An appropriate sum of weighted ratings had a positive predictive value (PPV) of 100% for ischemic stroke. With consolidated categories, the PPV was 97% when patients had the following: no neck stiffness; no atrial fibrillation but history of stroke/TIA and GCS > or =12, or no neck stiffness but atrial fibrillation. CONCLUSIONS: Among patients with acute stroke, clinical data can be used to identify a group with a high probability of ischemic stroke. There are slightly different results between both methods; while SMLR includes the four variables selected by CC, the latter included neither diastolic blood pressure nor hemiplegia/hemiparesia. However, CC results seem easier to understand and interpret than with SMLR.
Assuntos
Isquemia Encefálica/diagnóstico , Doença Aguda , Idoso , Fibrilação Atrial , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Comorbidade , Diástole , Emergências , Feminino , Escala de Coma de Glasgow , Cefaleia/etiologia , Humanos , Hipertensão/etiologia , Leucocitose/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Vômito/etiologiaRESUMO
Twenty-one adult volunteers (aged 27-32 years), who had been living in Mexico City for four continuous months (physicians working as fellows) were studied the first and sixteenth week of their stay in order to learn the effects of the pollutants contained in Mexico City's atmosphere on some serum biochemical parameters. The activity of serum superoxide dismutase (SOD) decreased after 16 weeks in comparison with the values obtained the first week (109.6 to 56.9 mU/mg protein; 50% less). In contrast, the inhibitory capacity of serum vs. induced in vitro lipoperoxidation increased in relation to the length of stay (22%). The serum levels of thiobarbituric-reactive material also decreased in almost 30% (from 6.10 to 4.12 nmol). The other lipoperoxides measured were unchanged (chromolipids and diene conjugation). We propose that this may be as a result of the adaptative capacity of the human organism, within a pollutant atmosphere in which the ozone levels might participate in a decrease of SOD activity during chronic exposure, to air pollution.
Assuntos
Poluentes Atmosféricos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Superóxido Dismutase/sangue , Adaptação Fisiológica , Adulto , Exposição Ambiental , Humanos , México , Oxirredução , Estresse Oxidativo , Ozônio/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Saúde da População UrbanaRESUMO
OBJECTIVE: To assess whether apparently healthy subjects with a family history of systemic hypertension have a higher risk of presenting the insulin resistance syndrome. SUBJECTS: Three hundred and eighty-six subjects aged 20-65 years. SETTING: A middle socio-economic class urban community from Mexico City. METHOD: All subjects and, when necessary, their first-degree relatives, answered a questionnaire and underwent a physical examination with measurement of height, weight and blood pressure. Serum insulin, glucose, cholesterol and triglycerides were measured during fasting and 2 h after an oral load of 75 g glucose. RESULTS: A family history of systemic hypertension was present for 167 (43%) of the subjects, of whom 123 (31%) were obese. Subjects with a family history of hypertension had higher systolic blood pressures than did those without such a history (120 +/- 15 versus 115 +/- 10 mmHg). In the logistic regression model, the body mass index and age showed statistically significant effects on the fasting glucose:insulin ratio and on serum insulin levels after an oral load of glucose. When men and women were analysed separately, only in men were higher systolic and mean blood pressures and lower glucose:insulin ratios observed. In the logistic regression analysis the body mass index was a significant predictor of the glucose:insulin ratio and serum insulin levels after an oral load of glucose, especially in men. CONCLUSION: Apparently healthy male offspring of hypertensive parents have higher blood pressure levels and lower insulin sensitivities than do offspring of normotensive parents. Insulin resistance was related to obesity, but not to a family history of hypertension, as had previously been reported by other research groups.
Assuntos
Hipertensão/genética , Resistência à Insulina/genética , Adulto , Idoso , Pressão Sanguínea , Saúde da Família , Feminino , Humanos , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade , Fatores SocioeconômicosRESUMO
Clinical diagnosis of subarachnoid hemorrhage (SAH) is frequently misdiagnosed with intracerebral hemorrhage (ICH) or cerebral infarction (CI), which delays appropriate referral. This study was undertaken to create a clinical index to select, among stroke patients, those with the highest probability of having a SAH. Clinical data of patients with acute stroke were evaluated with the X2 and the Fisher exact test; a p value < 0.05 was considered significant. Significant variables were included in a "log-lineal regression analysis" where those with an odds ratio (OR) 95% confidence limits not including the unit were considered to construct an index using the odds ratio coefficient (C). The results indicated that of 197 records which were included, 22 cases of SAH and 175 of ICH or CI were demonstrated. Kappa coefficients for observer variation in clinical data retrieval was 0.91. After "log-lineal regression analysis" was carried out the following variables were significant: neck stiffness (C = 3, OR = 21); lack of focal neurologic signs (C = 2, OR = 6.88); and age < or = 60 years (C = 1.5, OR = 4.35). A fourth variable, seizures (C = 1, OR = 3.25), was marginally significant (p = 0.07), but added predictive value to the index. The positive predictive values of the sum of the coefficients were: 0 = 0%; 1-2 = 3%; 2.5-3.5 = 21%; 4-5 = 40%; 6.5 = 75%; 7.5 = 100%. In conclusion, when a stroke patient shows neck stiffness, or any combination of young age, lack of focal neurologic signs or seizures (a score > or = 2.5, the index has a 91% sensitivity and 82% specificity), he/she must be referred to a tertiary care center.
Assuntos
Exame Físico , Hemorragia Subaracnóidea/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Hemorragia Cerebral/diagnóstico , Infarto Cerebral/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Músculos do Pescoço/fisiopatologia , Exame Neurológico , Variações Dependentes do Observador , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Encaminhamento e Consulta , Análise de Regressão , Estudos Retrospectivos , Convulsões/etiologia , Sensibilidade e Especificidade , Hemorragia Subaracnóidea/epidemiologiaRESUMO
The action of air pollutants, through their constituents, (O3, NO2, tobacco smoke) are capable of causing damage due to their lipoperoxidative properties or, indirectly, by inducing production of free radicals. As a consequence of photochemical processes, the ozone levels in the atmosphere of Mexico City are generally higher (mean of 0.325 ppm; period between 1987-1992) and may be harmful to health. Sixty two volunteers (medical doctors), aged 27-32 years, were divided into three groups. Group A was composed of those persons (17) who had never lived in Mexico City; a second group (B) (21) had recently arrived in Mexico City (1-8 days); and a third group (C) (24) who had permanently resided in Mexico City. Serum was obtained from fresh whole blood. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive materials were higher in group B while chromolipids and the serum inhibitory capacity (for lipoperoxidation) was higher in group C. The acute exposure to pollutants in group B apparently may have induced SOD as an antioxidant defense and was responsible for the increased level of TBA reactive material. In group C, the significant finding is better antioxidative defenses and slightly higher chromolipids.