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Aromatase Gene Polymorphisms Are Associated with Survival among Patients with Cardiovascular Disease in a Sex-Specific Manner  [PDF]
Amber L. Beitelshees,Julie A. Johnson,Megan L. Hames,Yan Gong,Rhonda M. Cooper-DeHoff,Jun Wu,Sharon Cresci,Cynthia X. Ma,Carl J. Pepine,Michael A. Province,John A. Spertus,Howard L. McLeod
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015180
Abstract: CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes.
Growth hormone-releasing hormone (GHRH) polymorphisms associated with carcass traits of meat in Korean cattle
Hyun Cheong, Du-Hak Yoon, Lyoung Kim, Byung Park, Yoo Choi, Eui Chung, Yong Cho, Eng Park, Il-Cheong Cheong, Sung-Jong Oh, Sung-Gon Yi, Taesung Park, Hyoung Shin
BMC Genetics , 2006, DOI: 10.1186/1471-2156-7-35
Abstract: By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428) and five marker haplotypes (frequency > 0.1) were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA.Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle.The successful application of marker-assisted selection in the commercial animal population will depend on the identification of genes, including identification of genes underlying quantitative traits, exploration of genetic polymorphisms that are involved in different phenotypes of quantitative traits, and understanding how these genes/polymorphisms interact with the environment or with other genes affecting economic traits.The growth hormone (GH) is essential for post-natal growth and general metabolism, and also plays an important role in lactation. Current knowledge indicates that GH exerts a key influence in nutrient use [1], mammary development [2], and growth [3]. There have been several reports of association between quantitative traits in cattle, such as growth performance and carcass merit, and polymorphisms in the GH gene [4-6].The regulation of GH synthesis and secretion is multifactorial, but the predominant regulators of GH are the hypothalamic hormones, GH-releasing hormone (GHRH), GH secretagogue (GHS), and somatostatin (SS) [7]. In spite of the functional importance of GHRH in the regulation of GH, only one PCR-restriction fragment-length polymorphism (RFLP) [8] has been reported in cattle.In this study, we examined GHRH as one of candidate gene
Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women
José A Riancho, Carmen Valero, María T Zarrabeitia, María T García-Unzueta, José A Amado, Jesús González-Macías
BMC Medical Genetics , 2008, DOI: 10.1186/1471-2350-9-112
Abstract: Four biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.Age, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p = 0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.Some common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.Osteoporosis is a complex disease characterized by reduced bone mineral density (BMD) and a propensity for fractures that results from the interaction of genetic and environmental factors. It has been estimated that the heritability of BMD is about 50–80% [1,2]. Estrogens play a critical role in bone homeostasis, and are essential for the acquisition and maintenance of bone mass. Estrogen deficiency accounts for the marked decrease in BMD when gonadal function ceases at the menopause, leading to the high incidence of osteoporotic fractures in postmenopausal women. However, it must be stressed that estrogens may still play a role after the menopause. In fact, the aromatization of androgenic precursors in the adipose tissue and other extragonadal tissues continues during life and an association between serum estradiol and certain polymorphisms of the aromatase gene has been reported [3]. Similar to other lipophilic hormones, estradiol circulates in the blood bound to proteins, specifically to sex hormone binding globu
Differential Association of Uncoupling Protein 2 Polymorphisms with Pattern Identification among Korean Stroke Patients: A Diagnostic System in Traditional Korean Medicine
Ji Hye Lim,Mi Mi Ko,Hoyoung Lee,Ho Yeon Go,Tae-Woong Moon,Min Ho Cha,Myeong Soo Lee
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/532078
Abstract: Uncoupling protein 2 (UCP2), a mitochondrial protein present in many organs and cell types, is known to dissipate the proton gradient formed by the electron transport chain. Its function is correlated with predictive parameters, such as obesity, diabetes, and metabolic syndromes. We analyzed the distribution of UCP2 polymorphisms in stroke patients diagnosed with one of the following four stroke subtypes based on the TKM standard pattern identification (PI): Qi-deficiency (QD), Dampness and Phlegm (D&P), Yin-deficiency (YD), and Fire and Heat (F&D). We studied a total of 1,786 stroke patients (397/QD, 645/D&P, 223/YD, and 522/F&D, 586/normal). Genotyping for the G-1957A, G-866A and A55V UCP2 polymorphisms was performed using the TaqMan. G-866A and A55V were significantly associated with the D&P and H&F subtypes. The frequency of subjects with the A allele of G-866A was significantly lower than the frequency of subjects with the GG type. The A55V polymorphism was also shown similar effect with G-866A in the dominant model. In contrast, no SNPs were shown to be associated with the QD or YD subtypes in this study. These results showed that the G-866A and A55V UCP2 polymorphisms may be genetic factors for specific PI types among Korean stroke patients.
Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia
Katherine K Anagnostopoulou, Genovefa D Kolovou, Peggy M Kostakou, Constantinos Mihas, Georgios Hatzigeorgiou, Christina Marvaki, Dimitrios Degiannis, Dimitri P Mikhailidis, Dennis V Cokkinos
Lipids in Health and Disease , 2009, DOI: 10.1186/1476-511x-8-24
Abstract: We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h).In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup.In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.The mechanisms that control the cholesteryl ester transfer protein (CETP) have attracted attention, since plasma CETP concentration is associated with increased risk for premature atherosclerosis [1]. The CETP concentration and activity in plasma is dependent on several factors such as environmental components including dietary cholesterol [2], alcohol [3], smoking and obesity [4], gender [5], and genetic influence (e.g. polymorphism of CETP gene) [6-8]. CETP plays a major role in the remodeling of lipoprotein particles by mediating the transfer of high density lipoprotein (HDL) cholesteryl esters. When the level of triglyceride (TG)-rich lipoproteins is normal, CETP transfers
Factors associated with obesity among Korean adolescents  [PDF]
Gyu Jin Heo, So Young Nam, Soo-Kyung Lee
Health (Health) , 2013, DOI: 10.4236/health.2013.58180
Abstract:

Obesity has been a great interest of public health. Studies simultaneously examining various factors associated with obesity among adolescents have been limited. Therefore, this study aimed to examine how various factors (socio-economic status, sex, age, diet, and physical activity) were simultaneously associated with obesity among Korean adolescents. This study analyzed two nationally representative datasets: 2008 Korea National Health and Nutrition Examination and Survey (KNHANES) and 2008 Korea Youth Risk Behavior Web-based Survey (KYRBWS). A total of 900 adolescents (12-18 year-old) in KNHANES and 74,451 adolescents in KYRBWS were included in statistical analyses with SPSS 19.0. Overweight (5.7%) and obesity (13.9%) rates were determined in KNHANES, and KYRBWS showed somewhat lower rates. No significant associations between the various factors and obesity were found in KNHANES. However, the analysis of KYRBWS confirmed higher obesity risk for boys, lower economic status, inferquent high-energy/low-nutrient type food consumption, practicing moderate-intensity physical activity less than five days per week, spending more than 2 hours sitting per day, and having tried exercise or diet for weight control (p < 0.05). The results from the two national datasets seemed to generally agree that many of the various obesity risk factors were important among Korean adolescents, although the associations were mostly not significant in KNHANES. It seemed that obese adolescents tried to practice good dietary behaviors, but not necessarily physical activity, known to reduce obesity risk. Obesity policies should continue to help adolescents achieve an active lifestyle and healthy eating behaviors.

Association of the UCP-1 single nucleotide polymorphism A-3826G with the dampness-phlegm pattern among Korean stroke patients  [cached]
Lim Ji,Ko Mi,Moon Tae-Woong,Cha Min
BMC Complementary and Alternative Medicine , 2012, DOI: 10.1186/1472-6882-12-180
Abstract: Background Patients with stroke have various syndromes and symptoms. Through pattern identification (PI), traditional Korean medicine (TKM) classifies the several syndromes and symptoms of stroke patients into five categories: Fire-heat (FH), Dampness-phlegm (DP), Yin-deficiency (YD), Qi-deficiency (QD) and Blood-stasis (BS). DP has been associated with obesity and hyperlipidemia. Uncoupling protein-1 (UCP-1), which plays a major role in thermogenesis and energy expenditure can increase the risk of obesity and can be related metabolic disorders. In this study, we elucidated the association of three polymorphisms located in the UCP-1 promoter and coding region with DP among Korean stroke patients. Methods 1,593 patients with cerebral infarction (583/DP, 1,010/non-DP) and 587 normal subjects were enrolled. The genotypes A-3826G, G-1766A and Ala64Thr (G+1068A) for each subject were determined by polymerase chain reaction with TaqMan probes and five percent of subjects were re-genotyped by sequencing method to confirm the accuracy of genotyping. The results were analyzed using a multiple logistic regression model to evaluate the genetic associations: the UCP-1polymorphisms of normal versus those of DP subjects and those of normal versus those of non-DP subjects. Results A significantly higher percentage of subjects in the DP group possessed the A-3826G G allele than the A allele (OR=1.508, p=0.006). Furthermore, the number of subjects with the GG type of A-1766G was significantly lower in the non-DP group than the normal group in the recessive model (OR=0.606, p=0.042). In addition, an analysis of the relationship among 2 SNPs of UCP-1 and lipid serum concentration showed that the serum level of HDL cholesterol was significantly higher in subjects with the A-3826G G allele in the normal group (p=0.032). Serum triglyceride and HDL cholesterol were also associated with the A-1766G variant in the recessive model (p=0.002, p=0.046). Conclusions These results suggest that that the A-3826G and A-1766G UCP-1 polymorphisms, which are related to obesity, might be candidate genetic markers for the DP pattern in the TKM diagnosis system.
Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types
Seongwon Cha,Imhoi Koo,Byung L. Park,Sangkyun Jeong,Sun M. Choi,Kil S. Kim,Hyoung D. Shin,Jong Y. Kim
Evidence-Based Complementary and Alternative Medicine , 2011, DOI: 10.1093/ecam/nep162
Abstract: Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ? 1.1 kg/m2) and MC4R variants (effect size ? 0.64 kg/m2). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes.
The genetic polymorphisms of HER-2 and the risk of lung cancer in a Korean population
Uk Jo, Sle Han, Jae Seo, Kyong Park, Jae Lee, Hyo Lee, Jeong Ryu, Yeul Kim
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-359
Abstract: The frequencies of 4 polymorphisms of the HER-2 gene were examined by the polymerase chain reaction-restriction fragment length polymorphism or the single-nucleotide polymorphism-identification technology assay in the 407 lung cancer patients and 407 healthy controls.The frequencies of the 4 polymorphisms were not significantly different between patient and control groups in overall subjects. However, in the subgroup analysis, the 3 single nucleotide polymorphisms (-3444C>T, -1985G>T and P1170A C>G) showed statistically significant differences in the subgroups of females, non-smokers, and non-drinkers (p < 0.05). Additionally, we found the association between the risk of lung cancer and the polymorphisms of HER-2 gene in non-smoker subgroups with adenocarcinoma (p < 0.05).Our results suggest that the polymorphisms of the HER-2 gene are associated with an increased susceptibility to lung cancer in females, non-smokers and non-drinkers subgroups in the Korean population.Lung cancer is the worldwide leading cause of cancer-related death [1]. During the past decades, the rate of incidence and mortality of lung cancer in Korea have been increasing significantly and constantly[2]. Although lung cancer has been considered as a disease caused by smoking and environmental/occupational exposure, previous studies suggest that genetic factors may also contribute to the risk of lung cancer [3].Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation, and they may contribute to an individual's susceptibility to cancer [4,5]. Many previous studies have demonstrated that some polymorphisms of certain genes are associated with the risk of lung cancer, affecting either the gene expression or activities of enzymes [6-8].The HER-2 (also known as erbB-2 or neu and a member of the epidermal growth factor receptor family), proto-oncogene is located at chromosome 17q21 and encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity [9,10]. So
Association between FGFR1OP2/wit3.0 Polymorphisms and Residual Ridge Resorption of Mandible in Korean Population  [PDF]
Jee Hwan Kim, Min Young Oh, Janghyun Paek, Jaehoon Lee
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042734
Abstract: Background A previous study on the genetic association between single nucleotide polymorphisms in FGFR1OP2/wit3.0 and the long term atrophy of edentulous mandible hypothesized that the excessive jawbone atrophy after dental extraction may be associated with abnormal oral mucosa contraction induced by the FGFR1OP2/wit 3.0 gene. It was reported that the minor allele of rs840869 or rs859024 in FGFR1OP2/wit3.0 was associated with the excessive atrophy of edentulous mandible. The present study represents an attempt to replicate the results of this previous study and to examine the genetic association between polymorphisms in FGFR1OP2 and residual ridge resorption of mandible in a Korean population. Methodology/Principal Findings 134 subjects (70.46±9.02 years) with partially or completely edentulous mandible were recruited. The mandibular bone height was measured following the protocol of the American College of Prosthodontists (ACP). From 24 subjects, seven variants in FGFR1OP2 were discovered and four of them were novel. Selected SNPs that are not in high LD at r2 threshold of 0.8 were genotyped for the remaining population. There was no frequency of the minor allele of SNP rs859024 in Korean population. SNP rs840869 was not associated with residual ridge resorption (p = 0.479). The bone height of the subject with the ss518063493 minor allele (8.52 mm) was shorter than that of those subjects with major alleles (18.96±5.33 mm, p = 0.053). Conclusions/Significance The patient with minor allele of ss518063493 may be associated with excessive atrophy of edentulous mandible whereas the patients with that of rs840869 are not associated in Korean population. The result from this study may assist in developing a novel genetic diagnostic test and be useful in identifying Koreans susceptible to developing excessive jawbone atrophy after dental extraction.
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