RESUMEN
BACKGROUND: Allergic rhinitis, a known risk factor for asthma onset, often accompanies mouth breathing. Mouth breathing may bypass the protective function of the nose and is anecdotally considered to increase asthma morbidity. However, there is no epidemiological evidence that mouth breathing is independently associated with asthma morbidity and sensitization to allergens. In this study, we aimed to clarify the association between mouth breathing and asthma morbidity and allergic/eosinophilic inflammation, while considering the effect of allergic rhinitis. METHODS: This community-based cohort study, the Nagahama Study, contained a self-reporting questionnaire on mouth breathing and medical history, blood tests, and pulmonary function testing. We enrolled 9804 general citizens of Nagahama City in the Shiga Prefecture, Japan. RESULTS: Mouth breathing was reported by 17% of the population and was independently associated with asthma morbidity. The odds ratio for asthma morbidity was 1.85 (95% CI, 1.27-2.62) and 2.20 (95% CI, 1.72-2.80) in subjects with mouth breathing alone and allergic rhinitis alone, which additively increased to 4.09 (95% CI, 3.01-5.52) when mouth breathing and allergic rhinitis coexisted. Mouth breathing in nonasthmatics was a risk for house dust mite sensitization, higher blood eosinophil counts, and lower pulmonary function after adjusting for allergic rhinitis. CONCLUSION: Mouth breathing may increase asthma morbidity, potentially through increased sensitization to inhaled allergens, which highlights the risk of mouth-bypass breathing in the 'one airway, one disease' concept. The risk of mouth breathing should be well recognized in subjects with allergic rhinitis and in the general population.
Asunto(s)
Asma/epidemiología , Asma/etiología , Respiración por la Boca , Adulto , Anciano , Asma/diagnóstico , Biomarcadores , Estudios de Cohortes , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Morbilidad , Oportunidad Relativa , Vigilancia de la Población , Pruebas de Función Respiratoria , Factores de Riesgo , AutoinformeRESUMEN
BACKGROUND/PURPOSE: Perceived age may be a better predictor of mortality rate than chronological age. We have demonstrated that perceived age was a significant biomarker for carotid atherosclerosis in Japanese. However, it remains to be determined which skin parameter is associated with atherosclerosis. The purpose of this study is to analyze the relationship between 10 facial skin-aging parameters and atherosclerosis in 169 middle-aged to elderly Japanese women who participated. METHODS: Facial photographs were taken under a shadowless lamp from three directions using a high-resolution digital camera. The digital images of each subject were analyzed using computer software and various parameters of skin aging such as pigmentation, wrinkles, and skin color were quantified. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis. RESULTS: Facial pigmentation showed a significant correlation with carotid IMT, even after correction for age (r = 0.13, P = 0.03), and with visceral fat area. Stepwise regression analysis indicated that facial pigmentation was associated with carotid IMT via visceral fat area. CONCLUSION: Facial pigmentation may be a useful biomarker for carotid atherosclerosis in Japanese women.
Asunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/epidemiología , Cara/patología , Pigmentación de la Piel , Piel/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Colorimetría/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Japón/epidemiología , Persona de Mediana Edad , Fotograbar/métodos , Prevalencia , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P<0.0001; Pearsons correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P=0.049) and max carotid IMT (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.
Asunto(s)
Enfermedades de las Arterias Carótidas/genética , Polimorfismo de Nucleótido Simple , Transaminasas/genética , Adulto , Anciano , Enfermedades de las Arterias Carótidas/etiología , Grosor Intima-Media Carotídeo , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: A recent genome-wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non-European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function. METHODS: Study subjects were 1190 general Japanese persons (66.0 ± 8.9 years old). Asymptomatic cerebrovascular damage, including lacunar infarctions, microbleeds, periventricular hyperintensity and deep and subcortical white matter hyperintensity (DSWMH), was evaluated by brain magnetic resonance imaging. RESULTS: A polymorphism rs3744028 was significantly associated with DSWMH grade (P = 0.015) but not periventricular hyperintensity, lacunar infarction, and microbleeds. Although age, hypertension, insulin resistance, B-type natriuretic peptide, and carotid atherosclerosis were also correlated with DSWMH, association of the genotype was independent of these environmental risk factors. In contrast, the risk allele had a protective effect against reduced cognitive function. CONCLUSION: Susceptibility of the 17q25 locus may be conserved beyond ethnic differences. Genetic variants may have bipolar effects on brain histological and functional changes.
Asunto(s)
Trastornos Cerebrovasculares/genética , Trastornos Cerebrovasculares/patología , Cromosomas Humanos Par 17/genética , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Fibras Nerviosas Mielínicas/patología , Anciano , Pueblo Asiatico/genética , Pueblo Asiatico/psicología , Trastornos Cerebrovasculares/diagnóstico , Femenino , Humanos , Masculino , Neuroimagen/psicología , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVES: To clarify whether serum creatinine to cystatin C ratio (CCR), a marker of muscle mass and muscle function may be used as a simple marker of bone property. DESIGN: A cross-sectional analysis. SETTING: A general population-based observation study. PARTICIPANTS: 1,606 middle-aged to elderly (≥50 years, mean age: 66.9 ± 7.5 years old) men (n = 642) and post-menopausal women (n = 964). MEASUREMENT: Speed of sound (SOS) at the calcaneal bone was used as a surrogate marker of bone mineral density. The cross-sectional area of the muscle at the mid-thigh was measured using computed tomography. RESULTS: There was significant linear correlation between the quartiles of CCR and SOS (Q1: 1,495 ± 25, Q2: 1,499 ± 24, Q3: 1,507 ± 26, Q4: 1,511 ± 25 m/sec; P < 0.001) even in a sex-separated analysis. This association was independent of major covariates (Q1: ß = -0.126, P < 0.001; Q2: ß = -0.096, P = 0.001; Q3: ß = -0.022; P = 0.412, Q4: reference) and the mid-thigh muscle mass, while creatinine alone or eGFR did not show clear association with SOS. CONCLUSION: The CCR may be used as a simple marker of bone property independently of muscle mass in a general population with preserved renal function.
Asunto(s)
Densidad Ósea/fisiología , Creatinina/sangre , Cistatina C/sangre , Anciano , Estudios Transversales , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated. SUBJECTS: We analyzed 2806 community-dwelling middle-aged to elderly subjects (61+/-14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. RESULTS: FTO genotype was significantly associated with current body mass index (BMI; TT 23.2+/-3.2, TA 23.7+/-3.2, AA 24.4+/-3.2 kg m(-2), P=2.5 x 10(-6)) and frequency of obesity (26.6, 32.0, 43.0% respectively, P=2.0 x 10(-4)). Age- and sex-adjusted odds ratio for obesity was 1.30 (P=0.004) in TA and 2.07 (P=0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P=0.001), Age-, sex- and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P=0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P=0.015), and the frequency of obesity (P=0.284). CONCLUSION: FTO genotype is an independent risk factor for future development of obesity.
Asunto(s)
Pueblo Asiatico/genética , Diabetes Mellitus Tipo 2/genética , Obesidad/genética , Proteínas/genética , Receptor de Melanocortina Tipo 4/genética , Anciano , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Genotipo , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Polimorfismo de Nucleótido Simple , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Several studies have reported that the circulating concentration of hepatocyte growth factor (HGF) was increased in individuals with clinically overt atherosclerotic disease, including coronary heart disease and peripheral arterial disease. However, whether changes in the circulating concentration of HGF are associated with early atherosclerotic changes in apparently healthy individuals remains to be determined. OBJECTIVE: To investigate the relationship between the plasma concentration of HGF and carotid arterial remodeling. METHODS: Plasma concentrations of HGF were measured in 201 community-dwelling healthy residents free from any medications and signs and history of cardiovascular disease. Carotid intima-media thickness (IMT) and carotid internal diameter were determined by ultrasonography with a 7.5 MHz probe. The study participants were divided into four groups according to the presence or absence of carotid atherosclerosis (presence of plaque, IMT > or = 0.85 mm) and carotid arterial dilatation (diameter > or = 7.0 mm). RESULTS: Carotid arterial remodeling, atherosclerosis or dilatation, or combinations thereof, was associated with significantly greater concentrations of plasma HGF. Among risk factors, plasma HGF was significantly associated with advanced age (> or = 65 years), current smoking and diabetes mellitus, whereas sex, obesity, hypertension and hypercholesterolemia did not affect plasma concentrations of HGF. Multiple regression analysis showed that plasma HGF was independently associated with carotid arterial remodeling (atherosclerosis, dilatation, or both) in addition to age and systolic blood pressure. CONCLUSIONS: These results indicate that the plasma concentration of HGF increases in relation to carotid arterial remodeling, independently of known risk factors for atherosclerosis. These findings further support a possible role of HGF in atherosclerosis.
Asunto(s)
Arterias Carótidas/fisiopatología , Enfermedades de las Arterias Carótidas/fisiopatología , Factor de Crecimiento de Hepatocito/sangre , Arteriosclerosis Intracraneal/fisiopatología , Anciano , Anciano de 80 o más Años , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/fisiología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Concentración Osmolar , Valores de Referencia , Factores de Riesgo , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , Ultrasonografía , Vasodilatación/fisiologíaAsunto(s)
Angiotensinógeno/genética , Proteínas de Unión a Calmodulina/genética , Hipertensión/genética , Polimorfismo Genético , Alelos , Sustitución de Aminoácidos , Presión Sanguínea , Femenino , Genotipo , Humanos , Hipertensión/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Sodio/metabolismoAsunto(s)
Hipertensión/etiología , Postura , Anciano , Análisis de Varianza , Presión Sanguínea , Humanos , Hipertensión/epidemiología , Japón/epidemiología , PrevalenciaRESUMEN
Central aortic blood pressure (BP), obtained from radial arterial waveform using the transfer function method (TFM), has been shown to have prognostic value independently of brachial BP. In this study, the relationship between peripheral systolic BP (SBP) and aortic SBP was evaluated. We further investigated whether TFM-derived aortic SBP can be estimated by information obtained from the radial waveform. The radial waveform was analysed to obtain the first peak of radial SBP (SBP1), second peak of radial SBP (SBP2), radial augmentation index (AI) (radial (SBP2-DBP)/(SBP1-DBP) x 100 and aortic SBP and AI using TFM in 233 subjects in the supine position. Measurements were repeated after changing position to the prone position. The constructed equation was validated in 149 community residents with different backgrounds. Radial SBP2 was closer to TFM-derived aortic SBP compared with brachial SBP. TFM-derived aortic SBP was approximated by the equation: aortic SBP=18.9-radial SBP2-0.03 x HR-0.214 x radial AI (r2=0.992). The equation was also applicable to predicting aortic SBP in the prone position as well as in different populations (mean difference between predicted aortic SBP and TFM-derived aortic SBP: -0.01+/-1.34 and 1.05+/-1.47 mm Hg, respectively). Radial arterial waveform analysis can be used for estimation of TFM-derived aortic SBP.
Asunto(s)
Aorta/fisiología , Determinación de la Presión Sanguínea/métodos , Arteria Braquial/fisiología , Arteria Radial/fisiología , Sístole/fisiología , Adulto , Anciano , Presión Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Posición Prona/fisiología , Reproducibilidad de los Resultados , Posición Supina/fisiologíaRESUMEN
The risk factor-gene interaction in carotid atherosclerosis was investigated in 205 community-dwelling healthy subjects aged 50 years or more in Japan. The intima-media thickness (IMT) of the common carotid artery was evaluated by ultrasonography with a 7.5-MHz probe. Gene polymorphisms were determined for each subject with angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C, and apolipoprotein E (apoE) genotypes. There was no genotype-specific difference in carotid IMT among any genes examined. Combinations of genotypes did not increase carotid IMT compared with subjects without these genotypes. In the total population, multiple regression analysis showed that age, systolic blood pressure (SBP), sex, and body mass index (BMI) were significantly associated with carotid IMT. However, the association between risk factors and IMT was genotype-specific. Age was significantly associated with IMT in ACE D carriers, but not in subjects with the ACE II genotype. Analysis of covariance adjusted with other risk factors showed that the age-dependent change in IMT was significantly different between subjects with the ACE II genotype and the ACE D carriers (F[1.196] = 4.97; P = 0.027). Similarly, the regression of IMT on SBP was significantly different between AGT TT and AGT MT + MM (F[1.196] = 7.20; P = 0.0079). The regression of IMT on BMI was also significantly different between apo E4 carriers and noncarriers (F[1.196] = 6.78; P = 0.0099). Furthermore, general linear model analysis with risk factors, genotype, and risk factor-genotype interactions revealed that the age*ACE genotype interaction, the SBP*AGT genotype interaction, and the BMI*apoE genotype interaction were significantly associated with IMT. These findings further support the role of risk factor-gene interaction in carotid atherosclerosis.
Asunto(s)
Arteriosclerosis/genética , Arterias Carótidas/patología , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Arteriosclerosis/epidemiología , Arterias Carótidas/diagnóstico por imagen , Femenino , Genotipo , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Isoformas de Proteínas , Sistema Renina-Angiotensina/genética , Factores de Riesgo , UltrasonografíaRESUMEN
Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting results have been reported about the association between MTHFR gene polymorphism and sclerotic lesions of the common carotid arteries. The effect of age-gene interaction on carotid arterial remodeling was investigated in elderly subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid arteries by ultrasonography in 326 patients (mean age +/- standard deviation, 73 +/- 12 years) and studied relations among the known risk factors for atherosclerosis, including MTHFR gene polymorphism and its interactions with age and sex. Of the 326 subjects studied, 136 had MTHFR genotype CC, 136 genotype CT, and 54 genotype TT. The three groups did not differ with respect to background factors such as age, history of cigarette smoking, blood pressure, lipids or uric acid, or in the incidence of atherosclerotic diseases. Spearman's rank correlation revealed a significant relationship between gender, age, Brinkman index, systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C), uric acid, and MTHFR gene polymorphism. Multiple regression analysis using intima-media complex thickness (IMT) as a criterion variable and risk factors, including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorphism (P = 0.039) was a significant independent explanatory variable for IMT, along with gender (male) (P < 0.001), age (P < 0.001), systolic blood pressure (SBP) (P = 0.047), total cholesterol (T-C) (P < 0.001), and HDL-C (P < 0.001). Furthermore, a general linear model analysis revealed that interaction between age and MTHFR gene polymorphism was significantly associated with IMT, independently of age, SBP, T-C, and HDL-C in male subjects. However, age-gene interaction was not observed in female subjects. The findings of the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further support the role of risk factor-gene interaction in common carotid atherosclerosis.