Osteoporosis is a common metabolic bone disease characterized by low bone mineral density (BMD) with an increased risk of fracture. Low bone mass results from an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts. Microphthalmia-associated transcription factor (MITF) plays a critical role in osteoclast development and thus is an important candidate gene affecting bone turnover and BMD. In order to investigate the genetic effects of MITF variations on osteoporosis, we directly sequenced the MITF gene in 24 Koreans, and identified fifteen sequence variants. Two polymorphisms (+227719C > T and +228953A > G) were selected based on their allele frequencies, and then genotyped in a larger number of postmenopausal women (n = 560). Areal BMD ($g/cm^2$) of the anterior-posterior lumbar spine and the non-dominant proximal femur was measured by dual-energy X-ray absorptiometry. We found that the MITF + 227719C > T polymorphism was significantly associated with low BMD of the trochanter (p = 0.005-0.006) and total femur (p = 0.02-0.03) (codominant and dominant models), while there was no association with BMD of the lumbar spine. The MITF+228953A > G polymorphism was also associated with low BMD of the femoral shaft (p = 0.05) in the recessive model. Haplotype analysis showed that haplotype 3 of the MITF gene (MITF-ht3) was associated with low BMD of the trochanter (p = 0.03-0.05) and total femur (p = 0.05) (dominant and codominant models). Our results suggest that MITF variants may play a role in the decreased BMD of the proximal femur in postmenopausal women.
The $\beta$3-adrenergic receptor ($\beta$3AR) plays a major role in thermogenesis and lipolysis in brown and visceral adipose tissue, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of $\beta$3AR gene polymorphism on the risk of hyperglycemia in 980 Korean women who attended a weight loss program in a local clinic. Each subject s height, weight, BMI, WHR, obesity index and body composition were measured. The genotype of the $\beta$3AR gene in codon 64 was analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, of total and HDL cholesterol, and of TG were determined. Genotype distributions were as follows : 67% WW type, 31% WR type, and 2% RR type. Among the many measured parameters, fasting glucose levels were significantly higher in the WR/RR type compared with the WW type (p=0.0ll). When the subjects were divided into two groups by a fasting blood glucose level higher or lower than 6.105mmol/L (110mg/dl), the frequency of hyperglycemia showed a significant difference in relation to $\beta$3AR genotype as measured by $\X^2$-analysis (p=0.014); the frequency of hyperglycemia was significantly higher (at 24.8%) in WR/RR type subjects, compared to 18.2% in WW type subjects. When all of the measured parameters were included in stepwise logistic regression analyses to find the risk factors for hyperglycemia, the odds ratios for hyperglycemia were 1.573 (p=0.0ll) for the WR/RR type of the $\beta$3AR gene, 1.053 (p=0.001) for TG, 1.044 (p=0.037) for BMI, and 1.026 for age (p=0.031). These data suggest that the WR/RR genotype of the $\beta$3AR has a very strong association with increased blood glucose level and might be a significant risk factor for hyperglycemia among Korean women.
Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Man, Dong-Liang;Shang, Hong
Asian Pacific Journal of Cancer Prevention
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v.13
no.7
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pp.3165-3172
/
2012
Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.
Background: Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in South-east Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to N-nitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing. CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for these enzymes may alter their expression or function and may therefore affect an individuals susceptibility regarding OSF and oral cancer. The present study was therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2 and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the Northern India population. A total of 95 histopathologically confirmed cases of OSF with history of areca nut chewing not less than 1 year and 80, age and sex matched controls without any clinical signs and symptoms of OSF with areca nut chewing habit not less than 1 year were enrolled. DNA was extracted from peripheral blood samples and polymorphisms were analyzed by PCR-RFLP method. Gene polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p = 0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also observed to be significant. However, no such association was observed for the CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.
Gallstone is the most common disease of the biliary system. Korean has experienced an increase in the percentage of cholesterol gallstones. The major risk factors associated with cholesterol gallstones are age, gender as well as obesity. This study was designed to determine the prevalence of gallstones in the last three years and evaluate the associated risk factors in the population who underwent health screening. The study population consisted of 2,484 males and 2,212 females who visited the health promotion center in Dalseogu, Daegu in Korea from January 2011 to December 2013. Each participant in the study had their biliary system gallbladder examined using ultrasonography. Classified as underweight, normal weight or overweight using the population of obese according to the body mass index, and classified according to mood diagnosis of diabetes presented by the American Diabetes Association. Fasting blood glucose and number of liver function, the divided the control group by referring to the normal liver function values used herein. The geological map, I was classified as NCEP APT III. A showed of total 148 people were found to have gallstones. The prevalence of sex among 148 patients (3.15%) 84 men (1.79%) and 64 women 1.36%) which shows significantly there is little difference. 1.84% 40 years and below, 3.38% 40's showed age prevalence was 4.66% in 50's and above. In addition, Total-cholesterol was at the most in 52 people, LDL-cholesterol in 398 people, Triglyceride in 36 people, HDL-cholesterol in 19 people. The abnormal group, was created from the total-cholesterol categories from a physical examination of a subject that has been found to be gallstones in the gallbladder. A result of conducting the univariate analysis shows the prevalence of gallstones, a correlation that is meaningful. The logistic regression analysis of multiple ages was chosen to show risk factors age independent cholelithiasis. In spite of the conclusion, gallstones are not displayed in relation to the metabolic syndrome but in order to clarify this, not only the subject of a health examination is needed but, a further study of the general public when possible.
Park, So-Yoon;Kang, Seok Jeong;Choi, Kwang Hae;Park, Yong Hoon;Lee, Young Hwan
Clinical and Experimental Pediatrics
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v.51
no.7
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pp.747-753
/
2008
Purpose : Diabetes mellitus is a major risk factor for the development of cardiovascular disease. Early atherosclerotic changes in the arterial walls begin in adolescence and the risk factors are associated with its development. To assess the usefulness of carotid artery intima-media thickness (IMT), as a marker of early atherosclerosis, we evaluated the structural and functional characteristics of the carotid artery and investigated their relationshop with the metabolic and anthropometric parameters in children and adolescents with type 1 diabetes. Methods : For this study, we enrolled 23 children with type 1 diabet and 19 age and sex-equivalent healthy children as the control group. Metabolic and anthropometric parameters such as serum lipid levels, plasma glycated hemoglobin (HbA1c), and body mass index were measured after a 12-h fasting period. The carotid artery IMT was measured by a high-quality ultrasound system, and compliance, and distensibility were calculated by an equation. Results : There were no significant differences between the 2 groups with regard to the sex ratio, age, blood pressure and serum cholesterol levels' however, HbA1c levels were significantly higher in the diabetic children ($8.5{\pm}1.8$ vs. $5.0{\pm}0.2$, P=0.001). Ultrasonographic findings showed that compared with the control group, the diabetic group had higher IMT ($0.45{\pm}0.06mm$ vs. $0.41{\pm}0.04mm$, P=0.04), but there were no significant differences in compliance and distensibility. The HbA1c (P=0.002) and high-density lipoprotein cholesterol (P=0.026) levels were independent IMT predictors in the diabetic group. Conclusion : Here, the carotid artery IMT was higher in the diabetic group, and it is correlated with atherosclerotic risk factor. Thus, carotid IMT could be evaluated as a marker of early atherosclerosis in diabetic children.
Effective nutrition educations for prevention of chronic diseases for the general population are of great importance these days. The purpose of this study was to evaluate the feasibility of nutrition education for cardiovascular risk factor reduction by e-mail education in male workers. The participants were divided into three groups by age; 28-39 age group, 40-49 age group, and 50-59 age group who got regular checkups for anthropometry and biochemistry. The 1 year program consisted of 15 topics containing information about metabolic syndrome (MS) and healthy eating behavior (intake of salt, fat and alcohol). Seven hundred thirty nine participants volunteered for the study [28-39 age group, n = 240; body mass index (BMI) = 24.9 $\pm$ 2.7 kg/m$^2$: 40' group, n = 276; BMI = 24.8 $\pm$ 2.6 kg/m$^2$: 50' group, n = 223; BMI = 24.9 $\pm$ 2.7 kg/m$^2$]. Percentage body fat (p < 0.05) and percentage of abdominal fat (p < 0.05), total cholesterol (p < 0.05), systolic blood pressure (p < 0.05), and diastolic blood pressure (p < 0.05) were significantly decreased in all participants after the 1 year program. The total number of participants who had MS was decreased from 216 to 199 and especially the incidence of MS was decreased 27% in the group of subjects who were under the age 39. The e-mail worksite nutrition education program shows a substantial contribution to the development of effective CVD and chronic disease control and lifestyle nutrition educations that are applicable to and attractive for the large population at risk.
Adrenergic receptors play a major role in thermogenesis and lipolysis in brown and visceral adipose tissues, and have been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of $\beta$2-adrenergic receptor ($\beta$2AR) and $\beta$3-adrenergic receptor ($\beta$3AR) genotypes on hyperglycemia and obesity in the Korean population. A representative sample consisting of 530 Korean men and women were measured for height, weight, BMI, WHR, obesity index and body composition. The genotypes of $\beta$2AR polymorphism in codon 27 and $\beta$3AR polymorphism in codon 64 were analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, total cholesterol, HDL cholesterol and triglyceride were determined. The frequencies of $\beta$2AR and $\beta$3AR genotype were: both wild type, 62.5% ; only $\beta$2AR variant type, 12.8% ; only $\beta$3AR variant type, 18.8% ; and both variant type, 5.8% ; the frequency of E and R alleles were 0.098 and 0.137, respectively. Among the physiological parameters, fasting glucose level was significantly higher in subjects with both variant type compared with the three other types (p <0.05), Subjects with both variant type had 12%, 12% and 9.3% increases in serum glucose levels compared with wild type, only $\beta$2AR variant type, and only $\beta$3AR variant type, respectively. When logistic regression analysis was conducted to estimate the risk for hyperglycemia, the subjects were selected for fasting blood glucose concentrations of more than 6.105 m㏖/L (110 mg/dL), and the odds ratios were 1.215 (p=0.636) for only $\beta$2AR variant type,1.659 (p=0.089) for only $\beta$3AR variant type, and 3.078 (p=0.011) for both variant type. These results suggest that the interaction of $\beta$2AR and $\beta$3AR variant genotypes has a strong association with increased glucose levels, and might be a significant risk factor for hyperglycemia among Korean subjects.
Background: Shift work increases the risk of chronic diseases, including metabolic diseases. However, studies on the relationship between shift work and renal function are limited. The aim of this study was to investigate the association between shift work and a decreased glomerular filtration rate (GFR). Methods: Data were evaluated for 1,324,930 workers who visited the Korean Medical Institute from January 1, 2016 to December 31, 2020 and underwent a health checkup. Daytime workers were randomly extracted at a ratio of 1:4 after matching for age and sex. In total, 18,190 workers aged over 40 years were included in the analyses; these included 3,638 shift workers and 14,552 daytime workers. Participants were categorized into the shift work group when they underwent a specific health checkup for night shift work or indicated that they were shift workers in the questionnaire. The odds ratio was calculated using a conditional logistic regression to investigate the relevance of shift work for changes in GFR. Results: 35 workers in the shift group and 54 in the daytime group exhibited an estimated GFR (eGFR) value of < 60 mL/min/1.73m2 (p < 0.01). The difference in eGFR values between two checkups differed significantly depending on the type of work (p < 0.01); the difference in the shift work group (-9.64 mL/min/1.73 m2) was larger than that in the daytime work group (-7.45 mL/min/1.73 m2). The odds ratio for eGFR reduction to < 60 mL/min/1.73 m2 in the shift group versus the daytime group was 4.07 (95% confidence interval: 2.54-6.52), which was statistically significant. Conclusions: The results of this study suggest that eGFR decreases by a significantly larger value in shift workers than in daytime workers; thus, shift work could be a contributing factor for chronic kidney disease (CKD). Further prospective studies are necessary to validate this finding and identify measures to prevent CKD in shift workers.
Few studies have examined short tenn responses to the different contents of carbohydrate or fat in the meal, although long tenn effects of the high fat meal have been considered as compound risk factor for metabolic disorders. The aim of this study was to investigate the postprandial changes of plasma glucose, insulin and lipids upon intakes of high carbohydrate or high fat meal in young healthy women. Subjects were randomly assigned to either the high carbohydrate meal (HCM, 75% carbohydrate, n=13) or the high fat meal (HFM, 60% fat, n=12) groups. The meals were prepared as isocaloric typical Korean menu. Blood samples were obtained prior to and 30, 60, 90, 120, 180 and 240 minute after the meal. There were no significant differences on fasting blood parameters including glucose, insulin, lipids concentrations between the groups prior to the test. The HCM had higher blood glucose and insulin concentrations, reached the peak at 30 min and maintained for 240 min compared to the HFM (P<0.05). The HFM had higher plasma triglyceride (TG) and free fatty acid (FFA) concentrations, reached the peak at 120 min and maintained for 240 min compared to the HCM (P<0.05). It is concluded that macronutrients content in the meal may be an important determinant of postprandial substrate utilization in healthy women.
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