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1.
BMC Med Genet ; 21(1): 160, 2020 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-32807123

RESUMEN

BACKGROUND: Diabetes is mostly assessed by the fasting glucose level. Several studies reported that serum fasting glucose levels and cardiovascular disease are associated with MC4R. METHODS: A total of 4294 subjects participated in this study. There were 1810 subjects with cardiovascular disease among the 4294 subjects. We used multivariate linear regression models and multiple logistic regression analysis. RESULTS: Individuals with the TC/CC genotype had a 1.29-fold higher risk of diabetes than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.29; 95% CI, 1.04-1.60). For healthy subjects, the association was significant in women (OR, 1.99; 95% CI, 1.01-3.93). Men with the TC/CC genotype had a 1.21-fold higher risk of cardiovascular disease than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.21; 95% CI, 1.04-1.41). The relationship between MC4R and cardiovascular disease was stronger in lean men (OR, 1.40; 95% CI, 1.12-1.74, p = 0.0028) than in overweight men. CONCLUSIONS: This study suggests that the rs17782313 SNP in MC4R is related to diabetes and the SNP is also associated with cardiovascular disease in lean men.


Asunto(s)
Enfermedades Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Receptor de Melanocortina Tipo 4/genética , Glucemia/metabolismo , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Oportunidad Relativa , República de Corea
2.
BMC Med Genet ; 19(1): 68, 2018 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-29720110

RESUMEN

BACKGROUND: Several genome-wide association studies (GWAS) for serum fasting glucose levels have reported HHEX as possibly causal. The objective of this study was to examine the joint effect of smoking on the association of diabetes with the HHEX rs5015480 polymorphism among Korean subjects. METHODS: This replication study included a total of 4240 individuals, and multivariate linear regression and multiple logistic regression models were used. We examined the combined effect of smoking on the relationship between HHEX rs5015480 and diabetes. RESULTS: The rs5015480 SNP in the HHEX gene was related to the mean FBS level (effect per allele, 1.572 mg/dL, p = 0.0122). Females with the CC genotype had a 2.68 times higher (range, 1.05-6.82 times) risk of diabetes than those with the TT/TC genotype. Although the association was stronger in female subjects (OR, 4.46; 95% CI, 1.15-17.3, p = 0.0304) among healthy individuals (N = 2461), the association between HHEX and diabetes was much stronger in male heavy smokers (OR, 4.03; 95% CI, 1.19-13.6, p = 0.0247) than in nonsmokers (p = 0.9709) and ex-smokers (p = 0.2399). The interaction of smoking was also statistically significant (P for interaction =0.0182). CONCLUSIONS: This study clearly demonstrates that a genetic variant in HHEX influences fasting glucose levels in Korean women and male heavy smokers.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Proteínas de Homeodominio/genética , Polimorfismo de Nucleótido Simple , Fumar/genética , Factores de Transcripción/genética , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , República de Corea , Factores de Riesgo , Factores Sexuales , Fumar/metabolismo
3.
Immun Ageing ; 15: 13, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29755573

RESUMEN

BACKGROUND: The pathogenesis of asthma, which is an allergic lung disease, is associated with a variety of allergens such as house dust mite, pollen, and mould, IgE containing serum IgE and allergen-specific-IgE, and inflammatory cytokines including thymus and activation-regulated chemokine (TARC)/CCL17. Because aging is an essential factor in the pathogenesis of asthma, we examined biomarkers related to asthmatic subjects depending on age. RESULTS: Physiological indices such as FEV1(forced expiratory capacity in 1 s), FEV1 (% predicted), and FEV1/FVC(forced vital capacity) (%) in asthmatic subjects were lower than those in normal subjects. Total IgE, Der p1 specific IgE, and Der f1 specific IgE were elevated in serum of asthmatics relative to normal individuals. Regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5 in serum and interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein (MCP)-1/CCL2, RANTES, and macrophage inflammatory protein (MIP)-1α/CCL3 in bronchoalveolar lavage fluid (BALF) of asthmatic subjects were higher than in normal individuals. Upon classification of experimental groups depending on age, physiological indices and Der p1-specific IgE (class) were decreased in middle aged adult and elderly adult groups relative to the young adult group. TARC levels in serum were strongly elevated in the elderly adult group relative to the young adult and the middle aged adult groups. TARC in serum was related to total IgE in serum in the elderly adult group. CONCLUSIONS: Taken together, although TARC in serum and BALF is not different between normal and asthmatic individuals, TARC increases in serum of elderly asthmatic subjects. The level of TARC has a positive effect on the level of IgE in the elderly adult group. These findings may help us better understand the relationship of pathogenesis of allergic diseases and aging.

4.
J Hum Genet ; 61(5): 405-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26763873

RESUMEN

High-density lipoprotein (HDL) cholesterol levels are associated with a decreased risk of coronary artery disease. Several genome-wide association studies that have examined HDL cholesterol levels have implicated myosin light chain 2 regulatory cardiac slow (MYL2) as a possible causal factor. Herein, the association between the rs3782889 single-nucleotide polymorphism (SNP) in the MYL2 gene and HDL cholesterol levels was tested in the Korean population. A total of 4294 individuals were included in a replication study with MYL2 SNP rs3782889. SNP rs3782889 in the MYL2 gene was associated with mean HDL cholesterol level (effect per allele, -1.055 mg dl(-1), P=0.0005). Subjects with the CT/CC genotype had a 1.43-fold (range 1.19-1.73-fold) higher risk of an abnormal HDL cholesterol level (<40 mg dl(-1)) than subjects with the TT genotype. When analyzed by sex, the MYL2 association was stronger in men than that in women. When analyzed by body mass index (BMI), the MYL2 association was much stronger in male subjects with BMI ⩾26.44 kg m(-2) (odds ratio (OR)=2.68; 95% confidence interval (CI)=1.87-3.84; P<0.0001) than that in male subjects with BMI <26.44 kg m(-2). When compared with subjects having the TT genotype and BMI <26.44 kg m(-2), ORs (95% CI) were 3.30 (2.41-4.50) in subjects having the CT/CC genotype and BMI ⩾26.44 kg m(-2) (P for interaction <0.0001). Our results clearly demonstrate that genetic variants in MYL2 influence HDL cholesterol levels in Korean obese male subjects.


Asunto(s)
Miosinas Cardíacas/genética , HDL-Colesterol/sangre , Estudios de Asociación Genética , Cadenas Ligeras de Miosina/genética , Obesidad/sangre , Obesidad/genética , Adulto , Alelos , Biomarcadores , Comorbilidad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , República de Corea/epidemiología , Factores de Riesgo
5.
J Hum Genet ; 60(3): 139-45, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25608829

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial disease. Although smoking is a main risk factor for obstructive impairment, not all smokers develop this critical disease. We conducted a genome-wide association study to identify the association between genetic variants and pulmonary function and also examined how these variants relate to lung impairment in accordance with smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319) and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we analyzed the association between genetic variants (single-nucleotide polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using multivariate linear regression models. Similar analyses were conducted after stratification by smoking status. Four genome-wide significant signals in the FAM13A gene (the strongest signal at rs2609264, P=1.76 × 10(-7) in a combined set) were associated with FEV1/FVC. For the association with ratio, the effect size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 × 10(-7)) as compared with the TCAG haplotype (reference haplotype) in a combined set. There was also a significant interaction of FAM13A haplotypes with heavy smoking on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes also interacted with heavy smoking to affect the risk of reduced pulmonary function.


Asunto(s)
Proteínas Activadoras de GTPasa/genética , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Enfermedad Pulmonar Obstructiva Crónica/genética , Adulto , Pueblo Asiatico/genética , Secuencia de Bases , Estudios de Cohortes , Volumen Espiratorio Forzado/fisiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Haplotipos , Humanos , Modelos Lineales , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica/etnología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , República de Corea/epidemiología , Factores de Riesgo , Fumar/fisiopatología , Capacidad Vital/fisiología
6.
Am J Hum Genet ; 87(4): 545-52, 2010 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-20887962

RESUMEN

Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.


Asunto(s)
Adiponectina/sangre , Pueblo Asiatico/genética , Cadherinas/genética , Estudio de Asociación del Genoma Completo , Adulto , Presión Sanguínea , Índice de Masa Corporal , Línea Celular , Colesterol/sangre , Cartilla de ADN/genética , Femenino , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Análisis de Secuencia de ADN
7.
Rheumatol Int ; 33(1): 19-23, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22212408

RESUMEN

Elevated uric acid levels are associated with a variety of adverse health risks. Genome-wide association studies have identified several candidate genes associated with serum uric acid levels, including SLC2A9. We carried out a replication study of SLC2A9 variants in two Korean cohorts. A total of 961 participants in Seoul City were genotyped using a genome-wide marker panel, and 1,859 participants in the Bundang-Gu area were used for a replication study with a selected marker. Multivariate linear regression models were employed to test for genotypic effects on uric acid levels while adjusting for age, sex, and smoking status using an additive model. The top single nucleotide polymorphism associated with uric acid levels was rs4529048 in the SLC2A9 gene on chromosome 4 (P = 2.12 × 10(-6) in the Seoul City sample; P = 1.55 × 10(-9) in the Bundang-Gu sample). The meta-analysis P value for rs4529048 in the combined 2,820 individuals was 1.17 × 10(-14). This study demonstrates that genetic variants in SLC2A9 influence uric acid levels in Korean adults.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Hiperuricemia/genética , Polimorfismo de Nucleótido Simple , Ácido Úrico/sangre , Adulto , Cromosomas Humanos Par 4 , Estudios de Cohortes , Femenino , Humanos , Hiperuricemia/sangre , Hiperuricemia/etnología , Masculino , Metaanálisis como Asunto
8.
Mol Biol Rep ; 39(9): 8709-16, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22696189

RESUMEN

The antioxidant 3,4',5 tri-hydroxystilbene (resveratrol), a phytoalexin found in grapes, shows cancer preventive activities, including inhibition of migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of resveratrol on tumor metastasis, especially in human metastatic lung and cervical cancers is not clear. A non-cytotoxic dosage of resveratrol causes a reduction in the generation of reactive oxygen species, and suppresses phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration in both A549 and HeLa cells. Resveratrol also decreases both the expression and the enzymatic activity of matrix metalloproteinase-9 (MMP-9), and the promoter activity of PMA-stimulated MMP-9 is also inhibited. However, resveratrol does not affect either the expression or the proteolytic activity of MMP-2. Our results also show that resveratrol suppresses the transcription of MMP-9 by the inhibition of both NF-κB and AP-1 transactivation. These results indicate that resveratrol inhibits both NF-κB and AP-1 mediated MMP-9 expression, leading to suppression of migration and invasion of human metastatic lung and cervical cancer cells. Resveratrol has potential for clinical use in preventing invasion by human metastatic lung and cervical cancers.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Movimiento Celular/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Estilbenos/farmacología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Células HeLa , Humanos , Neoplasias Pulmonares/genética , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Metástasis de la Neoplasia , Especies Reactivas de Oxígeno/metabolismo , Resveratrol , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Activación Transcripcional , Neoplasias del Cuello Uterino/genética
9.
BMC Public Health ; 12: 54, 2012 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-22260168

RESUMEN

BACKGROUND: As well as biomedical risk factors, psychological factors have been reported to be related to mortality rate. The purpose of this study was to examine the relationship between life satisfaction and mortality in elderly people through an 11.8-year follow-up study of a prospective cohort. METHODS: Among 3,600 participants of the Kangwha Cohort Study who survived in 1994, 1,939 respondents of the Life Satisfaction Index (LSI)-A questionnaire were included (men, 821; women, 1118). The mortality risk for the period up to December 2005 was measured using the Cox Proportional Hazard Model. RESULTS: When the relationship between LSI and mortality was evaluated in men, the unsatisfied group with lower LSI scores showed a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.83) than the satisfied group with higher LSI scores. In women, the unsatisfied group showed a significantly higher risk of all-cause mortality (HR, 1.51; 95% CI, 1.18-1.92) and cardiovascular mortality (HR, 2.23; 95% CI, 1.30-3.85) than the satisfied group. CONCLUSION: We found that elderly people with a lower LSI score, regardless of gender, were at risk of increased mortality from all causes, and low LSI score was also associated with cardiovascular mortality.


Asunto(s)
Mortalidad , Satisfacción Personal , Anciano , Causas de Muerte , Estudios de Cohortes , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , República de Corea/epidemiología
10.
Gerontology ; 57(6): 490-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21358170

RESUMEN

BACKGROUND: Previous studies have shown links between cognitive impairment and hypertension as well as mortality. However, combined effects of these two conditions on mortality have not been fully explored. OBJECTIVE: To assess the combined effect of cognitive impairment and hypertension on all-cause mortality among the elderly people. METHODS: We followed a cohort of 2,496 residents in Kangwha County, ranging in age from 64 to 101 years as of March 1994, for all-cause mortality for 11.8 years up to December 31, 2005. We calculated hazard ratios (HR) for all-cause mortality by cognitive status and blood pressure using the Cox proportional hazards model after having controlled for confounding factors. RESULTS: 1,189 people (47.6%) died during the 11.8 years of follow-up. The HR associated with severe cognitive impairment increased from 2.15 (95% CI: 1.30, 3.54) for prehypertension over 2.68 (95% CI: 1.60, 4.48) for stage 1 hypertension to 3.60 (95% CI: 1.99, 6.49) for stage 2 hypertension in women. A mortality risk of 3.67 (95% CI: 2.05, 6.57) was observed among men who had both mild cognitive impairment and stage 2 hypertension. CONCLUSION: Individuals with coexisting cognitive impairment and hypertension are at an increased risk of all-cause mortality compared with those with cognitive impairment or hypertension alone.


Asunto(s)
Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/mortalidad , Hipertensión/complicaciones , Hipertensión/mortalidad , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/psicología , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/mortalidad , Estudios de Cohortes , Comorbilidad , Recolección de Datos , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Factores de Riesgo
11.
Stroke ; 41(10): 2157-62, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20724719

RESUMEN

BACKGROUND AND PURPOSE: The purpose of this study was to examine combined effects of hypertension and binge drinking on the risk of mortality from cardiovascular disease in Koreans. METHODS: This study followed a cohort of 6100 residents in Kangwha County, aged ≥55 years as of March 1985, for cardiovascular mortality for 20.8 years up to December 31, 2005. We calculated hazard ratios (HRs) for cardiovascular mortality by blood pressure and binge drinking habits using the Cox proportional hazard model. Binge drinkers and heavy binge drinkers were defined as having ≥6 drinks on 1 occasion and ≥12 drinks on 1 occasion. RESULTS: After adjusting for total alcohol consumption, male heavy binge drinkers with Grade 3 hypertension had a 12-fold increased risk of cardiovascular mortality (HR, 12.7; 95% CI, 3.47 to 46.5), whereas male binge drinkers with Grade 3 hypertension had a 4-fold increased risk of cardiovascular mortality (HR, 4.41; 95% CI, 1.38 to 14.1) when compared with nondrinkers with normal blood pressure. However, in considering separate effects of heavy binge drinking and hypertension on the risk of cardiovascular mortality, HRs were rather low (HR of heavy binge drinkers, 1.88, 1.10 to 3.20; HR of hypertensives, 2.00, 1.70 to 2.35) compared with nondrinkers with normal blood pressure. CONCLUSIONS: Binge drinkers and heavy binge drinkers with Grade 3 hypertension showed a marked increase in cardiovascular mortality risk. Even after adjusting for total alcohol consumption, the former revealed 4.41 and the latter indicated 12.7 of HR for the risk of cardiovascular mortality.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Conducta de Ingestión de Líquido , Etanol/envenenamiento , Hipertensión/complicaciones , Anciano , Consumo de Bebidas Alcohólicas/mortalidad , Pueblo Asiatico , Presión Sanguínea , Estudios de Cohortes , Femenino , Humanos , Hipertensión/mortalidad , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Riesgo , Factores de Riesgo
12.
J Epidemiol ; 20(3): 204-11, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20234107

RESUMEN

BACKGROUND: Alcohol consumption is a known risk factor for cancers of the mouth, esophagus, liver, colon, and breast. In this study, we examined the association between alcohol consumption and digestive cancer mortality in Korean men and women. METHODS: A cohort of 6291 residents of Kangwha County who were aged 55 years or older in March 1985 were followed to 31 December 2005-a period of 20.8 years. We calculated the relative risks of cancer mortality with respect to the amount of alcohol consumed. Cox proportional hazard model was used to adjust for age at entry, smoking, ginseng intake, education status, and pesticide use. RESULTS: In men, the risks of mortality from esophageal cancer (relative risk [RR], 5.62; 95% confidence interval [CI], 1.45-21.77) and colon cancer (RR, 4.59; 95% CI, 1.10-19.2) were higher among heavy drinkers, as compared with abstainers. The risks of mortality from colon cancer and bile duct cancer rose with increasing alcohol consumption; these trends were positive and statistically significant (P = 0.04 and P = 0.02, respectively). When participants were stratified by type of alcoholic beverage, soju drinkers had higher risks of mortality from esophageal cancer and colon cancer than makkoli drinkers. In women, the risk of digestive cancer mortality was higher among alcohol drinkers than abstainers, but this difference was not statistically significant. CONCLUSIONS: Alcohol consumption increases mortality from esophageal cancer and colon cancer in men.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Neoplasias del Sistema Digestivo/etiología , Neoplasias del Sistema Digestivo/mortalidad , Anciano , Estudios de Cohortes , Neoplasias del Colon/etiología , Neoplasias del Colon/mortalidad , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores Sexuales
13.
Genet Epidemiol ; 32(6): 505-12, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18357615

RESUMEN

Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence around 1 in 700 live births. The Runt-related transcription factor 2 (RUNX2) gene has been suggested as a candidate gene for CL/P based largely on mouse models; however, no human studies have focused on RUNX2 as a risk factor for CL/P. This study examines the association between markers in RUNX2 and isolated, nonsyndromic CL/P using a case-parent trio design, while considering parent-of-origin effects. Case-parent trios from four populations (77 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 24 single nucleotide polymorphisms (SNPs) in the RUNX2 gene. We performed the transmission disequilibrium test on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test and the parent-of-origin likelihood ratio test (PO-LRT). When all trios were combined, the transmission asymmetry test revealed a block of 11 SNPs showing excess maternal transmission significant at the P<0.01 level, plus one SNP (rs1934328) showing excess paternal transmission (P=0.002). For the 11 SNPs showing excess maternal transmission, odds ratios of being transmitted to the case from the mother ranged between 3.00 and 4.00. The parent-of-origin likelihood ratio tests for equality of maternal and paternal transmission were significant for three individual SNPs (rs910586, rs2819861, and rs1934328). Thus, RUNX2 appears to influence risk of CL/P through a parent-of-origin effect with excess maternal transmission.


Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Impresión Genómica , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Patrón de Herencia , Corea (Geográfico) , Funciones de Verosimilitud , Desequilibrio de Ligamiento , Masculino , Maryland , Polimorfismo de Nucleótido Simple , Singapur , Taiwán
14.
Stroke ; 40(9): 2953-8, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19556525

RESUMEN

BACKGROUND AND PURPOSE: The purpose of this study was to examine the association between binge drinking and risks of mortality due to all causes of death with a focus on cerebrovascular disease in Korean men and women. METHODS: This study followed a cohort of 6291 residents in Kangwha County, aged > or =55 years in March 1985, for their cause-specific mortality for 20.8 years up to December 31, 2005. We calculated hazard ratio of mortality by experience or frequency of binge drinking using the Cox proportional hazard model. Binge drinking was defined as having > or =6 drinks on one occasion. RESULTS: In men, binge drinkers who drink daily had an increased risk of mortality from all causes (hazard ratio, 1.33; 95% CI, 1.11 to 1.60) as compared with nondrinkers. They showed much increased risks of mortality from total stroke (hazard ratio, 1.86; 95% CI, 1.16 to 2.99) and hemorrhagic stroke (hazard ratio, 3.39; 95% CI, 1.38 to 8.35). Female binge drinkers also showed an increased risk of mortality from cardiovascular disease as compared with female nondrinkers, but the outcome was not statistically significant. CONCLUSIONS: The results of this study suggest that frequent binge drinking has a harmful effect on hemorrhagic stroke in Korean men. These findings need to be confirmed in further studies.


Asunto(s)
Consumo de Bebidas Alcohólicas/mortalidad , Accidente Cerebrovascular/mortalidad , Anciano , Pueblo Asiatico , Femenino , Estudios de Seguimiento , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Accidente Cerebrovascular/etiología
15.
Stroke ; 40(11): 3428-35, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19696422

RESUMEN

BACKGROUND AND PURPOSE: The association between body mass index and mortality caused by subtypes of stroke among postmenopausal women in terms of smoking status and age at menopause remains controversial. METHODS: The data were derived from a cohort study of 3321 with 17.8 years of follow-up (1985 to 2002). Hazard ratios (HRs) and 95% CIs for strokes as related to body mass index were estimated by Cox proportional hazard models adjusted for age, hypertension, smoking, drinking, occupation, education, self-reported health, and age at menopause. A stratified analysis was conducted by age at menopause and smoking status. RESULTS: The obese group (body mass index >or=27.5 kg/m(2)) had higher risks of total stroke mortality (HR, 1.59; 95% CI, 1.05 to 2.42) and hemorrhagic stroke mortality (HR, 2.91; 95% CI, 1.37 to 6.19) than the normal weight group (18.5or=50. For the obese group of the former, the HR of total stroke was 2.04 (95% CI, 1.25 to 3.34) and that of hemorrhagic stroke 6.46 (95% CI, 2.42 to 17.25). CONCLUSIONS: In this prospective study, obesity raised the risks of total stroke mortality and hemorrhagic stroke mortality among Korean menopausal women. It was more evident with women who experienced menopause at age <50. The obese group of ever smokers was at an increased risk of ischemic stroke mortality.


Asunto(s)
Pueblo Asiatico , Índice de Masa Corporal , Menopausia , Posmenopausia , Fumar/mortalidad , Accidente Cerebrovascular/mortalidad , Factores de Edad , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Corea (Geográfico) , Menopausia/fisiología , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/mortalidad , Posmenopausia/fisiología , Estudios Prospectivos , Factores de Riesgo , Fumar/efectos adversos , Fumar/fisiopatología , Accidente Cerebrovascular/fisiopatología
16.
Hum Genet ; 126(3): 385-94, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19444471

RESUMEN

This study examined the association between markers in transforming growth factor alpha (TGFA) and isolated, non-syndromic cleft lip with/without palate (CL/P) using a case-parent trio design, considering parent-of-origin effects. We also tested for gene-environmental interaction with common maternal exposures, and for gene-gene interaction using markers in TGFA and another recognized causal gene, IRF6. CL/P case-parent trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 17 single nucleotide polymorphisms (SNPs) in TGFA. The transmission disequilibrium test was used to test individual SNPs, and the parent-of-origin likelihood ratio test (PO-LRT) was used to assess parent-of-origin effects. We also screened for possible gene-environment interaction using PBAT, and tested for gene-gene interaction using conditional logistic regression models. When all trios were combined, four SNPs showed significant excess maternal transmission, two of which gave significant PO-LRT values [rs3821261: P = 0.004 and OR(imprinting) = 4.17; and rs3771475: P = 0.027 and OR(imprinting) = 2.44]. Haplotype analysis of these two SNPS also supported excess maternal transmission. We saw intriguing but suggestive evidence of G x E interaction for several SNPs in TGFA when either individual SNPs or haplotypes of adjacent SNPs were considered. Thus, TGFA appears to influence risk of CL/P through unconventional means with an apparent parent-of-origin effect (excess maternal transmission) and possible interaction with maternal exposures.


Asunto(s)
Labio Leporino/complicaciones , Labio Leporino/genética , Fisura del Paladar/complicaciones , Fisura del Paladar/genética , Factor de Crecimiento Transformador alfa/genética , Femenino , Genotipo , Humanos , Factores Reguladores del Interferón/genética , Desequilibrio de Ligamiento , Masculino , Exposición Materna , Modelos Genéticos , Padres , Polimorfismo de Nucleótido Simple , Mapeo de Interacción de Proteínas , Singapur
17.
N Engl J Med ; 355(8): 779-87, 2006 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-16926276

RESUMEN

BACKGROUND: Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial. METHODS: We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters). RESULTS: In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age. CONCLUSIONS: Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.


Asunto(s)
Índice de Masa Corporal , Obesidad/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Factores de Confusión Epidemiológicos , Femenino , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Sobrepeso , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Riesgo , Delgadez/mortalidad
18.
Diabetes Metab Res Rev ; 25(3): 259-65, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19214966

RESUMEN

BACKGROUND: Although adiponectin is generally known as a predictor of metabolic syndrome, potential of adiponectin as a predictor for metabolic syndrome in type 2 diabetes is debated. The purpose of this study is to determine the association between adiponectin and metabolic syndrome in patients with type 2 diabetes. METHODS: Adiponectin and the risk of metabolic syndrome were examined among 1013 type 2 diabetes patients who visited Huh's Diabetes Center from January 2003 to June 2006. Adiponectin levels were classified into quartile groups, and metabolic syndrome was defined according to the standard of National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III. Insulin sensitivity was directly assessed using the short insulin tolerance test (SITT) (Kitt: %/ min). RESULTS: Adiponectin was significantly correlated with metabolic syndrome components. The age-adjusted correlations between adiponectin and clinical parameters including metabolic components were significant; adiponectin was negatively correlated with waist circumference, diastolic blood pressure and triglyceride, and positively correlated with high-density lipoprotein (HDL) cholesterol. Subjects with metabolic syndrome showed lower adiponectin levels than those without metabolic syndrome. After multivariate adjustment, participants with lower adiponectin levels also had a higher risk for metabolic syndrome (OR for lowest quartiles 2.21; 95% CI, 1.51-3.24). Metabolic syndrome risk was stronger among those with low adiponectin and severe insulin resistance simultaneously. This study has shown additive effects of adiponectin and insulin resistance on metabolic syndrome. CONCLUSIONS: In type 2 diabetic patients, the adiponectin was a useful predictor of metabolic syndrome independent of potential confounding variables.


Asunto(s)
Adiponectina/sangre , Diabetes Mellitus Tipo 2/sangre , Síndrome Metabólico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Resistencia a la Insulina , Masculino , Síndrome Metabólico/etiología , Persona de Mediana Edad , Factores de Riesgo
19.
J Clin Gastroenterol ; 43(9): 869-75, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19398926

RESUMEN

BACKGROUND AND AIMS: Obesity has been postulated as contributing to the risk of nonalcoholic steatohepatitis. With the surging obesity epidemic, an ensuing epidemic of nonalcoholic steatohepatitis and its sequelae is of concern. The objectives of this clinical research study were to examine the association between body mass index (BMI) and serum aminotransferase levels. METHOD: A study was carried out on 1,166,847 Koreans (731,560 men and 435,287 women), 30 to 95 years of age, who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation from 1992 to 1995. RESULTS: Across the range of BMI values (<18.5 to >or=32 kg/m) in men, alanine aminotransferase (ALT) was estimated to increase by 18.8 U/L and aspartate aminotransferase (AST) increased by 7.1 U/L. In women, ALT increased by 9.9 U/L, whereas AST increased by 4.5 U/L. In men, interactions between BMI and alcohol consumption were significant (P<0.001) for ALT and AST, but the degree of effect modification was quantitatively minor. However, ALT and AST levels were somewhat higher in heavy alcohol drinkers than in nondrinkers. For women, the relationship of aminotransferase levels with BMI did not vary by alcohol consumption. The relationship of BMI with aminotransferase weakened with increasing age. CONCLUSIONS: In Korea, ALT and AST are strongly associated with BMI and increased progressively from the lowest to the highest strata of BMI. The association of BMI with aminotransferase levels was modified by age and sex.


Asunto(s)
Alanina Transaminasa/sangre , Pueblo Asiatico/estadística & datos numéricos , Aspartato Aminotransferasas/sangre , Índice de Masa Corporal , Pruebas Enzimáticas Clínicas , Hígado Graso/etiología , Obesidad/complicaciones , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/etnología , Biomarcadores/sangre , Estudios Transversales , Hígado Graso/diagnóstico , Hígado Graso/etnología , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Obesidad/etnología , Oportunidad Relativa , Estudios Prospectivos , República de Corea , Medición de Riesgo , Factores de Riesgo , Factores Sexuales
20.
Endocr J ; 56(1): 73-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18840926

RESUMEN

OBJECTIVE: To measure the association between smoking and serum adiponectin, taking into consideration insulin resistance and obesity. MATERIAL AND METHODS: The cross-sectional study was carried out in Seoul, Korea in 2006. Waist circumference (WC), body mass index (BMI), and serum adiponectin were measured in 2,500 healthy Korean men. Multiple linear regression models were used to assess the association of smoking status with serum adiponectin level. WC, BMI, and homeostasis model assessment (HOMA) were classified into two groups according to median values. RESULTS: The mean adiponectin concentrations were 6.6 microg/ml and 7.3 microg/ml in current smokers and non-smokers. After adjusting for age, BMI, and alcohol consumption, mean log adiponectin levels decreased by 0.064 microg/ml in current smokers compared with non-smokers (P = 0.0190). Mean log adiponectin levels also decreased by 0.030 and 0.095 microg/ml in moderate and heavy smokers compared to non-smokers. The relationship between adiponectin and smoking was similar between the high and low insulin resistance, BMI, and WC groups. CONCLUSIONS: These results suggest that serum adiponectin levels are associated with smoking status. These data also support that lower serum adiponectin concentrations in smokers may not be dependent on insulin resistance status or obesity.


Asunto(s)
Salud , Fumar/sangre , Adiponectina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/sangre , Consumo de Bebidas Alcohólicas/epidemiología , Índice de Masa Corporal , HDL-Colesterol/sangre , Estudios Transversales , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Fumar/epidemiología , Circunferencia de la Cintura , Adulto Joven
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