Obesity associates with vasomotor symptoms in postmenopause but with physical symptoms in perimenopause: a cross-sectional study.

BACKGROUND: Middle-aged women experience various menopausal symptoms during the menopause. These symptoms can affect their quality of life and health. Several epidemiological studies reported that obesity associates with menopausal symptoms. The aim of this cross-sectional study was to examine the associations between obesity and multiple menopausal symptoms at different stages of menopause in middle-aged Korean women. METHODS: The study population included women aged 44-56 years who visited a tertiary referral hospital for medical check-ups between November 2012 and March 2013 and were free from serious illness, could comprehend a questionnaire. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to assess the prevalence of menopausal symptoms. Overweight and obesity were defined as body mass index (BMI) of 23-24.9 and ≥25 kg/m2, respectively. RESULTS: Of the 2204 middle-aged women, 929 met the eligibility criteria. Of these, 533 (57.4%) and 396 (42.6%) were in perimenopause and postmenopause, respectively. In perimenopause, obese women were significantly more likely to have moderate/severe physical symptoms (MENQOL domain score ≥ 5) than normal or overweight women. In postmenopause, obese women were significantly more likely to have moderate/severe vasomotor symptoms. Multiple linear regression with adjustment for confounders showed that relative to normal weight, obesity in perimenopause and postmenopause associated independently with physical symptoms (beta coefficient = 0.35; P = 0.023) and vasomotor symptoms (beta coefficient = 0.68; P = 0.003), respectively. Overweight did not associate with menopausal symptoms. BMI did not associate significantly with psychosocial or sexual symptoms at either stage of menopause. CONCLUSIONS: Obese women had more frequent menopausal symptoms than normal or overweight women but the associated menopausal symptom differed depending on the menopausal stage. Further studies are required to confirm this result and identify the underlying mechanisms.

Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: results from the Korean Genome and Epidemiology Study.

AIMS/HYPOTHESIS: To examine the association between soybean products and risk of type 2 diabetes, we measured four isoflavone biological markers--genistein, daidzein, glycitein and equol--in a nested case-control study. METHODS: The study population was composed of 693 cases (316 women and 377 men) and 698 matched controls (317 women and 381 men) within the Korean Genome and Epidemiology Study. The concentrations of isoflavone biomarkers were measured using HPLC-MS/MS on plasma samples that were collected at baseline. A stratified analysis was undertaken to examine the association between plasma isoflavone concentrations and risk of type 2 diabetes according to sex and equol production. Logistic regression models were used to compute ORs and 95% CIs adjusted for confounders. RESULTS: In women, compared with the lowest quartile of plasma concentration of genistein, the highest quartile exhibited a significantly decreased risk of diabetes (OR 0.58, 95% CI 0.35, 0.95). When stratified by equol-producing status in women, the OR for diabetes in the highest vs the lowest quartile of genistein concentration was 0.31 (95% CI 0.16, 0.60) in equol producers, but genistein concentration was not associated with risk of diabetes in equol non-producers (p for interaction = 0.013). In men, isoflavone concentrations were not associated with risk of diabetes, regardless of equol-producing status. CONCLUSIONS/INTERPRETATION: High plasma concentrations of genistein were associated with a decreased risk of type 2 diabetes in women. This inverse association was prominent in equol-producing participants. These results suggest a beneficial effect of a high intake of soybean products on risk of type 2 diabetes in women.

Intake levels of dietary polyunsaturated fatty acids modify the association between the genetic variation in PCSK5 and HDL cholesterol.

BACKGROUND: A low serum level of high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 5 (PCSK5) modulates HDL-C metabolism through the inactivation of endothelial lipase activity. METHODS: Therefore, we analysed the effects of PCSK5 on HDL-C and investigated the association between genetic variation in PCSK5 and dietary polyunsaturated fatty acids (PUFAs) intakes in Korean adults and children. This population-based study which was conducted in South Korea included 4205 adults (43% male) aged 40-69 years and 1548 children (48.6% boys) aged 8-13 years. Dietary intake was assessed using a semiquantitative food frequency questionnaire in adults and modified 3-day food records in children. RESULTS: After adjustments for age and body mass index, we identified a significant association between SNP rs1029035 of the PCSK5 gene and HDL-C concentrations specifically for men in both populations (adults, p=0.004; children, p=0.003; meta, p=7×10(-4)). Additionally, the interaction between the PCSK5 rs1029035 genotype and dietary polyunsaturated fatty acids intake influenced serum HDL-C concentrations in men (adults, p=0.001; children, p=0.008). The deleterious effect of the C allele on serum HDL-C was present only when dietary PUFA intake was less than the dichotomised median level (adults, p=0.011; children, p=0.001). Serum HDL-C concentrations were decreased in men with the C allele genotype and low consumption of dietary PUFA including n-3 and n-6. CONCLUSION: According to these results, men carrying of the C allele were associated with low HDL-C concentrations and might exert beneficial effects on HDL-C concentrations following consumption of a high-PUFA diet.

Association between physical activity and menopausal symptoms in perimenopausal women.

BACKGROUND: Physical activity may be an effective way of preventing or attenuating menopause-related symptoms, and it has been shown to improve quality of life in menopausal women. However, there have been some inconsistencies regarding between exercise and menopausal symptoms, and study investigating this association has been scarce in Korea. In this study, the association between physical activity and menopausal symptoms in perimenopausal women in Korea was assessed. METHODS: This cross-sectional observational study was conducted between November 2012 and March 2013. In total, 2,204 healthy women aged 44-56 years were recruited from a healthcare center at the Kangbuk Samsung hospitals for investigating women's attitudes towards menopause. To investigate the influence of physical activity on perimenopause-associated symptoms, 631 perimenopausal women were selected for this study. Their physical activity levels were assessed using the International Physical Activity Questionnaire (IPAQ) short form. The Menopause-specific Quality of Life (MENQOL) questionnaire was used to assess menopause-related symptoms. RESULTS: The study participants were, on average, 48.5 ± 2.7 years old and had a mean body mass index of 22.8 ± 3.1 kg/m2. The total MENQOL score and the psychosocial and physical subscores exhibited U-shaped trends in relation to the level of physical activity. Multiple linear regression analysis adjusted for confounding variables showed that perimenopausal women who performed moderate physical activity reported significantly lower psychosocial (ß = -0.413, P = 0.012) and physical symptoms (ß = -0.445, P = 0.002) than women who performed low physical activity. By contrast, a high level of physical activity did not influence the MENQOL total score and subscores relative to the low activity group. In addition, no associations were observed between physical activity and the vasomotor and sexual symptoms in any group. CONCLUSIONS: Moderate level of physical activity was associated with reduced psychosocial and physical menopause symptoms in perimenopausal Korean women. Although these findings must be confirmed by prospective longitudinal studies, they suggest that physical activity may improve the symptoms of menopause, thereby increasing quality of life.

Rice-eating pattern and the risk of metabolic syndrome especially waist circumference in Korean Genome and Epidemiology Study (KoGES).

BACKGROUND: Metabolic syndrome poses a serious health threat in Asian countries. Rice is a staple food in Korea, and carbohydrate intake is associated with the risk of MetS. We hypothesized that various rice-eating patterns in a carbohydrate-based diet would have different effects on the risk of MetS. METHODS: Participants were 26,006 subjects enrolled in the Korean Genome and Epidemiology Study between 2004 and 2006. They were classified into four dietary patterns - white rice, rice with beans, rice with multi-grains, and mixed based on their food frequency questionnaire responses. We compared metabolic risk traits according to the rice-eating patterns. RESULTS: Nutrients consumption and the presence of MetS risk factors differed according to rice-eating patterns. In men odds ratio(OR) for central obesity was slightly elevated in mixed group(1.18). In women, the risk for central obesity and abnormal fasting glucose were lower in the rice with beans group (adjusted OR =0.79, 0.83 respectively) and central obesity in rice with multi-grains(adjusted OR=0.91) than the white rice group. In postmenopausal women, ORs for central obesity (0.78) and abnormal fasting glucose (0.75) in the rice with beans group and ORs for central obesity (0.83), abnormal HDL-cholesterol (0.87) and MetS(0.85) in the rice with multi-grains group was lower than those in white rice group. In premenopausal women, the risk for central obesity (OR=0.77) was reduced in the rice with beans group. CONCLUSION: The risk for MetS was lower in the rice with beans and rice with multi-grains groups compared with the white rice group, particularly in postmenopausal women.

The Korean undiagnosed diseases program: lessons from a one-year pilot project.

BACKGROUND: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea. RESULTS: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficient clinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinically diagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex, atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 in group II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (< 18 years old) and 59 (60.8%) were male. The primary symptoms for 80 patients (82.5%) were neurologic. During the one-year pilot study, 72 patients completed a diagnostic assessment including clinical and molecular genetic analyses; some patients also underwent pathological or biochemical analysis. Twenty-eight of these patients (28/72, 38.9%) achieved molecular genetic diagnosis. Thirteen patients were diagnosed based on traditional tests, including biochemical assay, single or targeted genetic analysis, and chromosomal microarray. We performed whole exome sequencing on 52 patients, among whom 15 (28.8%, 15/52) reached a final diagnosis. One new disorder was identified via international collaboration. CONCLUSIONS: Using an efficient clinical diagnostic workflow, this KUDP pilot study resulted in a fair diagnostic success rate, improving the potential for additional diagnoses and new scientific discovery of complex and rare diseases. KUDP also satisfied unmet needs for rare diseases with multisystem involvement, highlighting the value of emerging genomic technologies for further research into rare and still-undiagnosed conditions.

The "Jolly Fat" Effect in Middle-Aged Korean Women.

BACKGROUND: It has been hypothesized that depression and obesity are bi-directionally associated, and when overweight people appear to show a lower risk of depression, this supports the "Jolly Fat" hypothesis. The aim of this study was to examine the "Jolly Fat" hypothesis in middle-aged women in Korea, by different perceived stress levels. METHODS: We performed a cross-sectional study of 44 to 56 aged Korean women (n = 2201) who underwent a health check-up program at the healthcare centers of Kangbuk Samsung Hospital (Seoul and Suwon centers) in Korea. General and abdominal obesity were defined as body mass index ≥25 kg/m2 and waist circumference ≥85 cm, respectively. Depressive symptoms were measured by a Korean version of the Center for Epidemiologic Studies-Depression scale. The association between obesity and depressive symptoms was investigated by using multiple logistic regression analyses by different levels of perceived stress, with adjustment for potential confounding factors. RESULTS: The prevalence of general and abdominal obesity and depressive symptoms were 23.7%, 21.4%, and 16.5%, respectively. Women with general obesity were less likely to have depressive symptoms (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.25-1.00; p-value: 0.049) in the low-stress group. We also found that women with abdominal obesity had a 60% decrease in the odds of having depressive symptoms (OR: 0.40; 95% CI: 0.18-0.87; p-value: 0.02) in the low-stress group. No significant association was found in the high-stress group. CONCLUSIONS: These findings indicate that the relationship between obesity and depressive symptoms in the Korean middle-aged women supports the "Jolly Fat" hypothesis. Further, our results underscore the role of stress as an important potential mediator exerting effects on the association between obesity and depressive symptoms.

The Korea Nurses' Health Study: A Prospective Cohort Study.

BACKGROUND: The Korea Nurses' Health Study (KNHS) is a prospective cohort study of female nurses, focusing on the effects of occupational, environmental, and lifestyle risk factors on the health of Korean women. MATERIALS AND METHODS: Female registered nurses aged 20-45 years and living in the Republic of Korea were invited to join the study, which began in July 2013. They were asked to complete a web-based baseline survey. The study protocols and questionnaires related to the KNHS are based on the Nurses' Health Study 3 (NHS3) in the United States, although they were modified to reflect the Korean lifestyle. Participants were asked about demographic, lifestyle factors, disease history, occupational exposure, reproductive factors, and dietary habits during their adolescence: Follow-up questionnaires were/will be completed at 6-8 month intervals after the baseline survey. If a participant became pregnant, she answered additional questionnaires containing pregnancy-related information. RESULTS: Among 157,569 eligible female nurses, 20,613 (13.1%) completed the web-based baseline questionnaire. The mean age of the participants was 29.4 ± 5.9 years, and more than half of them were in their 20s. Eighty-eight percent of the participants had worked night shifts as a nurse (mean, 5.3 ± 4.3 nights per month). Approximately 80% of the participants had a body mass index below 23 kg/m2. Gastrointestinal diseases were the most prevalent health issues (25.9%). CONCLUSIONS: The findings from this prospective cohort study will help to identify the effects of lifestyle-related and occupational factors on reproductive health and development of chronic diseases in Korean women.

Habitual coffee intake, genetic polymorphisms, and type 2 diabetes.

BACKGROUND: The association between coffee intake and type 2 diabetes may be modulated by common genetic variation. OBJECTIVE: The purpose of this study was to examine the association between habitual coffee intake and the risk of type 2 diabetes and to determine whether this association varied by genetic polymorphisms related to type 2 diabetes in Korean adults. DESIGN AND METHODS: A population-based cohort study over a follow-up of 4 years was conducted. A total of 4077 Korean men and women aged 40-69 years with a normal glucose level at baseline were included. Coffee intake was assessed using a validated food frequency questionnaire, and incident type 2 diabetes or prediabetes was defined by oral glucose tolerance test or fasting blood glucose test. The genomic DNA samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 5.0, and nine single-nucleotide polymorphisms related to type 2 diabetes in East Asian populations were extracted. RESULTS: A total of 120 cases of type 2 diabetes and 1128 cases of prediabetes were identified. After adjustment for potential confounding factors, we observed an inverse association, but without any clear linear trend, between coffee intake and the combined risk of type 2 diabetes and prediabetes. We found that inverse associations between habitual coffee intake and the combined risk of type 2 diabetes and prediabetes were limited to those with the T-allele (GT/TT) of rs4402960 in IGF2BP2, those with the G-allele (GG/GC) of rs7754840 in CDKAL1, or those with CC of rs5215 in KCNJ11. CONCLUSION: We found a lower risk of prediabetes and type 2 diabetes combined with coffee intake among individuals with the GT/TT of IGF2BP2 rs4402960, GG/GC of CDKAL1 rs7754840, or CC of KCNJ11 rs5215, which are known to be related to type 2 diabetes in East Asians.

The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children.

BACKGROUND: Glucokinase regulator (GCKR) plays important roles in the regulation of glucokinase (GK) activity and the metabolism of glucose and lipids. We investigated whether the association between GCKR genetic variants with serum lipids in Korean adults is replicated in children, and whether these genetic influences might be modulated by dietary monounsaturated fatty acid relative to saturated fatty acid (MUFA:SFA) ratio. METHODS: We genotyped 711 children for GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric, biochemical, and dietary measurements. RESULTS: The major allele carriers of rs780094 and rs780092 in adults had significantly higher serum total cholesterol and triglycerides levels compared to noncarriers. Five variants in children, including rs780094 and rs780092, correlated similarly with high total and low-density lipoprotein (LDL) cholesterol. When the dietary MUFA:SFA ratio was dichotomized (MUFA:SFA≥1 or <1), the aggravating effects of the major allele on total cholesterol, LDL cholesterol, and triglycerides were only evident in the group in which MUFA:SFA ratio was <1. Additionally, we observed that the GCKR haplotype with a functional variant, rs1260326, influenced lower total and LDL cholesterol in children whose MUFA:SFA ratio was <1. CONCLUSION: We replicated the genetic association effect of GCKR on total cholesterol in children, and found that the interaction effects between GCKR genetic variants and the dietary MUFA:SFA ratio on lipid levels, were commonly observed in Korean adults and children.

Menopausal stages and serum lipid and lipoprotein abnormalities in middle-aged women.

OBJECTIVES: Whether menopausal stage is associated with abnormalities in serum lipid and lipoprotein profiles remains unclear; studies have been conducted mostly in Western populations. This study aimed to examine the prevalence of lipid and lipoprotein abnormalities by recently updated menopausal stages in middle-aged women. STUDY DESIGN: This study was cross-sectional analysis of 1553 women aged 44-56 years, who underwent a comprehensive health screening examination in the Kangbuk Samsung Hospital Total Healthcare Centers, Korea, during 2012-2013. Lipid and lipoprotein profiles including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipoprotein (a) (Lp(a)), apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B) were assessed. Prevalence ratios and 95% confidence intervals for lipid and lipoprotein abnormalities were estimated by menopausal stages as defined by the 2011 Stages of Reproductive Aging Workshop+10 criteria. RESULTS: Increased prevalence of lipid and lipoprotein abnormalities were observed across menopausal stages. The increased prevalence of high non-HDL-C was associated with the late menopausal transition and post-menopausal stages and was more pronounced in women with body mass index (BMI) <23 kg/m(2) than in those with BMI ≥23 kg/m(2) (P for interaction=0.006). Similarly, there was an interaction between BMI and menopausal stages in relation to high Apo B (P for interaction=0.05) and high Apo B/Apo A1 ratio (P for interaction=0.06). CONCLUSIONS: Our findings extend previous results and suggest that the increased prevalence of lipid and lipoprotein abnormalities was associated not only with the post-menopausal stage but also late menopausal transition period.

Prevalence and severity of menopause symptoms and associated factors across menopause status in Korean women.

OBJECTIVE: The present study investigated the prevalence and severity of menopause symptoms experienced by Korean women aged 44 to 56 years and their associated factors. METHODS: A cross-sectional study was performed on 2,201 women aged 44 to 56 years in health checkup centers between November 2012 and March 2013. The 29-item Menopause-Specific Quality of Life Questionnaire was used to assess vasomotor, psychosocial, physical, and sexual symptoms related to menopause. The guidelines for the classification of reproductive aging stages proposed at the Stages of Reproductive Aging Workshop were used. Multivariable linear regression analyses were performed to identify factors associated with severity of menopause symptoms. RESULTS: Among participants, 42.6% were premenopausal, 36.7% were perimenopausal, and 20.7% were postmenopausal. Although physical symptoms were the most severe menopause symptoms experienced by premenopausal and perimenopausal women, postmenopausal women reported sexual symptoms as the most bothersome. The mean scores for each domain increased from the premenopausal period through the postmenopausal period (P for trend < 0.001). The regression model revealed that age (for vasomotor and sexual symptoms) and obesity (for vasomotor and physical symptoms) were significantly associated with severity of menopause symptoms (P < 0.05). Physically active women had fewer severe physical symptoms related to menopause than inactive women. CONCLUSIONS: Postmenopausal women experience the most severe symptoms. Obesity and physical activity are the main modifiable factors associated with symptom severity. Further studies are needed to examine the effects of physical activity promotion and weight control interventions on preventing menopause symptoms in Korean women.

Relation of Dietary Glycemic Index and Glycemic Load to Coronary Artery Calcium in Asymptomatic Korean Adults.

The relation between glycemic index, glycemic load, and subclinical coronary atherosclerosis is unknown. The aim of the study was to evaluate the associations between energy-adjusted glycemic index, glycemic load, and coronary artery calcium (CAC). This study was cross-sectional analysis of 28,429 asymptomatic Korean men and women (mean age 41.4 years) without a history of diabetes or cardiovascular disease. All participants underwent a health screening examination between March 2011 and April 2013, and dietary intake over the preceding year was estimated using a validated food frequency questionnaire. Cardiac computed tomography was used for CAC scoring. The prevalence of detectable CAC (CAC score >0) was 12.4%. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest to the lowest quintile of glycemic index and glycemic load were 1.74 (1.08 to 2.81; p trend = 0.03) and 3.04 (1.43 to 6.46; p trend = 0.005), respectively. These associations did not differ by clinical subgroups, including the participants at low cardiovascular risk. In conclusion, these findings suggest that high dietary glycemic index and glycemic load were associated with a greater prevalence and degree of CAC, with glycemic load having a stronger association.

Menopausal stages and non-alcoholic fatty liver disease in middle-aged women.

OBJECTIVES: There is no established evidence regarding the influence of the menopausal transition period on non-alcoholic fatty liver disease (NAFLD). The goal of this study was to examine the association between menopausal stages and the prevalence of NAFLD in middle-aged Korean women. METHODS: This study was a cross-sectional analysis of 1559 women aged 44-56 years, who underwent a comprehensive health screening examination in the Kangbuk Samsung Hospital Total Healthcare Centers during 2012 and 2013. Information regarding menopause status was collected using a standardized, self-administered questionnaire. The presence of fatty liver was determined using ultrasonography. Menopausal stages were defined according to the criteria of the Stages of Reproductive Aging Workshop (STRAW+10) as follows: early menopausal transition was defined as a persistent difference in consecutive menstrual cycle length of seven or more days; late menopausal transition was defined as having an interval of amenorrhea of 60 days or more; post-menopause was defined as the absence of menstrual periods for 12 or more months since the last period; pre-menopause was defined as having a regular menstrual cycle and not meeting the above criteria. Odds ratios and 95% confidence intervals for NAFLD were estimated by menopausal stages. RESULTS: Of the 1559 women, 334 had NAFLD. A higher prevalence of NAFLD was observed across menopausal stages (p for trend <0.05). After adjusting for age, center, BMI, smoking status, alcohol intake, physical activity, educational level, parity and age at menarche, the odds ratios (95% CIs) for NAFLD comparing early transition, late transition, and post-menopause to pre-menopause were 1.07 (0.68-1.67), 1.87 (1.23-2.85), and 1.67 (1.01-2.78), respectively. CONCLUSIONS: This study performed in middle-aged Korean women suggests that there is an increased prevalence of NAFLD in the late menopausal transition as well as post-menopausal stages, independent of a variety of potential confounders. The findings of this study suggest that early intervention strategies implemented before women begin to experience the menopausal transition are needed to reduce the risk of NAFLD.

Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study.

BACKGROUND: Soy intake is associated with a lower risk of breast cancer. However, it is unclear whether the same reduction in risk associated with high soy intake is also applicable to familial or genetic breast cancer. OBJECTIVE: The aim of this study was to assess the dietary factors among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study (KOHBRA). DESIGN: The KOHBRA Study is an ongoing project composed of affected breast cancer patients and familial members of breast cancer cases with BRCA mutations. To assess the association between dietary diversity and breast cancer risk, an HR was estimated by comparing affected subjects with their familial nonaffected members. To assess the interaction between the combination of BRCA mutation and diet diversity, the case-only OR (COR) was estimated by comparing BRCA mutation carriers and noncarriers only in affected subjects. RESULTS: Soy product intake was associated with a lower risk of breast cancer in carriers (HR: 0.39; 95% CI: 0.19, 0.79 for the highest quartile). The highest quartile of meat intake was associated with a higher risk of breast cancer regardless of BRCA mutation in carriers (HR: 1.97; 95% CI: 1.13, 3.44) and noncarriers (95% CI: 1.41; 1.12, 1.78). The associations of meat intake and soybean intake for breast cancer were more prominent in BRCA2 mutation carriers. In the analysis with only cases, the highest quartile of soy intake, but not meat intake, was associated with BRCA-related breast cancer (COR: 0.57; 95% CI: 0.36, 0.91). CONCLUSION: Our study suggests that soy product consumption is associated with lower breast cancer risk and it had an interaction with BRCA mutation.

Recapitulation of the association of the Val66Met polymorphism of BDNF gene with BMI in Koreans.

Recent evidence suggests that brain-derived neurotrophic factor (BDNF) regulates food intake and the control of body weight. A common polymorphism in human BDNF, Val66Met (single-nucleotide polymorphism database (dbSNP) no. rs6265), impairs intracellular trafficking, resulting in the reduced secretion of BDNF. Several European studies have indicated that Val66Met is associated with BMI. In this study, we examined the association of the Val66Met polymorphism with BMI in Koreans (n = 20,270) from three independent epidemiological cohorts. All three studies observed a consistent association of this polymorphism with BMI, and their combined analysis demonstrated a robust correlation (ß = -0.17 ± 0.03 and P = 5.6 × 10(-8)). We also examined the effect of smoking on the link between Val66Met and BMI. The association of Val66Met with BMI was statistically significant only in the smoking group, reflecting a possible interaction between smoking and the BDNF polymorphism for BMI. Thus, we have confirmed BDNF as a genetic risk factor for BMI in an Asian population and hypothesize that the Val66Met mutation influences individual differences in BMI. In addition, smoking might interact with BDNF Val66Met to modulate BMI.

Dietary patterns and osteoporosis risk in postmenopausal korean women.

OBJECTIVES: The prevalence of osteoporosis and related fractures has increased rapidly in Korean women. Proper nutrition intake is associated with the prevention of osteoporosis. We analyzed the association between dietary patterns and the risk of osteoporosis during a 4-year follow-up in postmenopausal Korean women. METHODS: Postmenopausal women (n = 1,725) who participated in the Korean Genome and Epidemiology Study were enrolled. Food intake was assessed using a validated semiquantitative food frequency questionnaire, and a quantitative ultrasound device was used to measure the speed of sound at the radius and tibia. RESULTS: THREE MAJOR DIETARY PATTERNS WERE IDENTIFIED USING FACTOR ANALYSIS BASED ON BASELINE INTAKE DATA: traditional (high intake of rice, kimchi, and vegetables), dairy (high intake of milk, dairy products, and green tea), and western (high intake of sugar, fat, and bread). Multivariate Cox proportional hazards models were used to estimate relative risk for osteoporosis. An inverse association was detected between the dairy dietary pattern and the osteoporosis incidence [relative risk (RR): 0.63, 95% confidence interval (CI): 0.42-0.93, p-trend=0.055 in radius; RR: 0.56, 95% CI: 0.35-0.90, p-trend=0.048 in tibia]. Individuals in the highest quintile for the traditional dietary pattern (p-trend = 0.009 in tibia) and western dietary pattern (p-trend = 0.043 in radius) demonstrated a higher risk of osteoporosis incidence than those in the lowest quintile. CONCLUSION: These results suggested that high consumption of milk, dairy products, and green tea may reduce the risk of osteoporosis in postmenopausal Korean women.

Epidemiological profiles between equol producers and nonproducers: a genomewide association study of the equol-producing phenotype.

Equol is a daidzein (a phytoestrogen isoflavone) metabolite of gut bacteria, and the ability to produce equol varies between individuals and reduces the risks of several diseases. We tested the effects of equol production on health in Koreans and identified the genetic factors that determine the equol-producing phenotype. In 1391 subjects, the equol-producing phenotype was determined, based on measurements of serum equol concentrations. The anthropometric and blood biochemical measurements between equol producers and nonproducers were analyzed by LC-MS/MS. Genetic factors were identified in a genomewide association study (GWAS), and the interaction between genetic factors and the equol-producing phenotype was examined. We observed that 70.1 % of the study population produced equol. Blood pressure was significantly lower in equol producers (beta ± SE = -1.35 ± 0.67, p = 0.045). In our genomewide association study, we identified 5 single-nucleotide polymorphisms (p < 1 × 10(-5)) in HACE1. The most significant SNP was rs6927608, and individuals with a minor allele of rs6927608 did not produce equol (odds ratio = 0.57 (95 % CI 0.45-0.72), p value = 2.5 × 10(-6)). Notably, the interaction between equol production and the rs6927608 HACE1 SNP was significantly associated with systolic blood pressure (p value = 1.3 × 10(4)). Equol production is linked to blood pressure, and HACE1, identified in our (GWAS), might be a determinant of the equol-producing phenotype.

A prospective study investigating the association between environmental tobacco smoke exposure and the incidence of type 2 diabetes in never smokers.

PURPOSE: We studied a cohort of individuals to assess whether intensity of environmental tobacco smoke (ETS) exposure is associated with the incidence of type 2 diabetes. METHODS: Study subjects were selected from an ongoing population-based cohort of Korea Genome and Epidemiology Study. Participants of the baseline study 10,038 persons within the age range of 40 to 69 years old. Among 4,442 never smokers without prevalent diabetes, 465 type 2 diabetes cases were identified through biennial active follow-ups for a 6-year period. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) after adjustment for covariates. RESULTS: The risk of type 2 diabetes was higher in subjects exposed to ETS compared with the nonexposure group (HR = 1.41, 95% CI: 1.1-1.70). Daily exposure to ETS at home increased the risk of type 2 diabetes when compared with the risk level of nonexposure (HR = 1.46, 95% CI: 1.16-1.83). Over 4 hours exposure to ETS at home and in the workplace was associated with increased the risk of type 2 diabetes (HR = 1.96, 95% CI: 1.21-3.19). CONCLUSIONS: Our study suggests that ETS exposure is a significant risk factor for the development of type 2 diabetes with dose-response relationship.

Dietary pattern classifications with nutrient intake and health-risk factors in Korean men.

OBJECTIVE: This study was performed to identify dietary patterns in Korean men and to determine the associations among dietary patterns, nutrient intake, and health-risk factors. METHODS: Using baseline data from the Korean Health and Genome Study, dietary patterns were identified using factor analysis of data from a validated food-frequency questionnaire, and associations between these dietary patterns and health-risk factors were analyzed. RESULTS: Three dietary patterns were identified: 1) the "animal-food" pattern (greater intake of meats, fish, and dairy products), 2) the "rice-vegetable" pattern (greater intake of rice, tofu, kimchi, soybean paste, vegetables, and seaweed), and 3) the "noodle-bread" pattern (greater intake of instant noodles, Chinese noodles, and bread). The animal-food pattern (preferred by younger people with higher income and education levels) had a positive correlation with obesity and hypercholesterolemia, whereas the rice-vegetable pattern (preferred by older people with lower income and educational levels) was positively associated with hypertension. The noodle-bread pattern (also preferred by younger people with higher income and education levels) had a positive association with abdominal obesity and hypercholesterolemia. CONCLUSION: This study identifies three unique dietary patterns in Korean men, which are independently associated with certain health-risk factors. The rice-vegetable dietary pattern, modified for a low sodium intake, might be a healthy dietary pattern for Korean men.