Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms.

The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1-1.5 µM) as compared to ß-arbutin (IC50, 500-700 µM) or kojic acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders.

Marine Alga Ecklonia cava Extract and Dieckol Attenuate Prostaglandin E2 Production in HaCaT Keratinocytes Exposed to Airborne Particulate Matter.

Atmospheric particulate matter (PM) is an important cause of skin damage, and an increasing number of studies have been conducted to discover safe, natural materials that can alleviate the oxidative stress and inflammation caused by PM. It has been previously shown that the extract of Ecklonia cava Kjellman, a perennial brown macroalga, can alleviate oxidative stress in epidermal keratinocytes exposed to PM less than 10 microns in diameter (PM10). The present study was undertaken to further examine the anti-inflammatory effects of E. cava extract and its major polyphenolic constituent, dieckol. HaCaT keratinocytes were exposed to PM10 in the presence or absence of E. cava extract or dieckol and analyzed for their viability, prostaglandin E2 (PGE2) release, and gene expression of cyclooxygenase (COX)-1, COX-2, microsomal prostaglandin E2 synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E2 synthase (cPGES). PM10 treatment decreased cell viability and increased the production of PGE2, and these changes were partially abrogated by E. cava extract. E. cava extract also attenuated the expression of COX-1, COX-2, and mPGES-2 stimulated by PM10. Dieckol attenuated PGE2 production and the gene expression of COX-1, COX-2, and mPGES-1 stimulated by PM10. This study demonstrates that E. cava extract and dieckol alleviate airborne PM10-induced PGE2 production in keratinocytes through the inhibition of gene expression of COX-1, COX-2, mPGES-1, and/or mPGES-2. Thus, E. cava extract and dieckol are potentially useful natural cosmetic ingredients for counteracting the pro-inflammatory effects of airborne PM.

Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression.

Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis.

Dietary oleuropein inhibits tumor angiogenesis and lymphangiogenesis in the B16F10 melanoma allograft model: a mechanism for the suppression of high-fat diet-induced solid tumor growth and lymph node metastasis.

Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates melanoma progression in the B16F10 allograft model. In this study, we examined whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD-diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were subcutaneously injected and the primary tumor was resected 3 weeks later. OL suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD-induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2), lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1α and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2 macrophages (MΦs). All animals were euthanized 2.5 weeks after tumor resection. OL suppressed HFD-induced increases in lymph node (LN) metastasis; expression of VEGF-A, VEGF-C, and VEGF-D in the LN; and M2-MΦs and the size of adipocytes in adipose tissues surrounding LNs. Co-culture results revealed that the crosstalk between B16F10s, M2-MΦs, and differentiated 3T3-L1 cells under hypoxic conditions increased the secretion of VEGF-A and -D, which stimulated tube formation and migration of endothelial cells (HUVECs) and lymphatic endothelial cells (LEC), respectively. Additionally, OL directly inhibited the differentiation of 3T3-L1 preadipocytes and tube formation by HUVECs and LECs. The overall results indicated that dietary OL inhibits lipid and M2-MΦ accumulation in HFD-fed mice, which contributes to decreases in VEGF secretion, thereby leading to inhibition of angiogenesis and lymphangiogenesis.

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest.

Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.

Association of APOE Genotype with Bone Mineral Density in Men and Women: The Dong-gu and Namwon Studies.

Many studies have investigated relationships between APOE genotype and bone mineral density (BMD). However, the results of these studies have been inconsistent. Few studies have been carried out in Asian populations. We studied the relationship of the APOE gene polymorphism and BMD in two large population-based studies. The datasets included the Dong-gu Study (3575 men and 5335 women) and the Namwon Study (2310 men, 3512 women). Lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. APOE genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The APOE genotypes were classified into APOE E2 (E2/E2 and E2/E3), APOE E3 (E3/E3), and APOE E4 (E3/E4 and E4/E4). The genotype distribution of the study population was in Hardy-Weinberg equilibrium. There were no significant differences among APOE genotype groups in lumbar and femoral neck BMD in either cohort. Our data do not support the hypothesis that the APOE genotype is associated with BMD.

The association between vitamin D and parathyroid hormone and bone mineral density: the Dong-gu Study.

The primary objective of the present study was to investigate the relationship between 25-hydroxyvitamin D (25[OH]D) and areal bone mineral density (aBMD) in Korean subjects from the general population aged ≥50 years. This study included 8,857 individuals who completed the baseline survey of the Dong-gu study, which was conducted in Korea from 2007-2010. The participants who fulfilled the detailed inclusion criteria underwent assessment of the femoral neck and lumbar spine aBMD as well as measurement of serum 25(OH)D and parathyroid hormone (PTH) levels. After adjusting for other covariates and log-PTH values, the mean aBMD of the femoral neck exhibited a significant increase with increasing 25(OH)D levels in both males (p < 0.001) and females (p = 0.005). Additionally, the mean aBMD of the lumbar spine exhibited a significant increase with increasing 25(OH)D levels in males (p = 0.011) but not females (p = 0.252). After adjusting for covariates and log-25(OH)D values, the mean aBMD values of the femoral neck and lumbar spine showed significant decreases with increasing PTH levels in both males and females (p < 0.001). The present findings demonstrate that the aBMD of the femoral neck was significantly associated with 25(OH)D levels independent of PTH in both males and females and that the aBMD of the lumbar spine was significantly associated with 25(OH)D levels independent of PTH in males, but not females.

Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration.

Piceatannol, a polyphenol which exhibits anticancer activities, is found in grapes, red wine and berries. It has been shown to inhibit several transcription factor pathways. The present study was conducted to determine whether oral administration of piceatannol inhibits mammary tumor progression. 4T1 mammary carcinoma cells were injected into the mammary fat pad of syngeneic female BALB/c mice. Starting 1 day later, piceatannol (10- or 20-mg/kg body weight/day) was administered by oral gavage for 30 days. Piceatannol treatment reduced tumor growth. In tumor tissues, piceatannol treatment reduced the expression of transcription factors P-NFκB p65, P-STAT3 and HIF-1α and multiple proteins involved in regulation of cell cycle progression (Ki67, cyclin D1, cyclin A, CDK2, CDK4), angiogenesis (VEGF-A, VEGFR-2, VE-cadherin, CD31) and lymphangiogenesis (VEGF-C, LYVE-1), as well as macrophage infiltration. Piceatannol significantly increased apoptotic cells and expression of both Bax and cleaved caspase-3 but reduced Bcl-2 expression in tumor tissues. In addition, piceatannol reduced the number and volume of pulmonary tumor nodules and expression of MMP-9 in both lung and tumor. It also reduced tissue levels of cytokines/chemokines, including M-CSF and MCP-1. In vitro results revealed that piceatannol inhibited migration of 4T1 cells and monocytes, as well as secretion of MCP-1 and M-CSF by 4T1 cells. 4T1 cell-conditioned medium stimulated monocyte migration, which was suppressed by a CCR2 antibody. These results indicate that alteration in tumor microenvironment (macrophages, transcription factors, etc.) is an important mechanism by which piceatannol inhibits tumor proliferation, angiogenesis and lymphangiogenesis, leading to suppression of mammary tumor growth and metastasis.

Estimation of the cutoff value of vitamin D: the Dong-gu study.

BACKGROUND: Vitamin D plays an essential role in bone health and growth, but the optimal serum 25-hydroxyvitamin D (25(OH)D) concentration is not known. This study was performed to investigate the optimal 25(OH)D concentration in regard to parathyroid hormone (PTH) concentration in the Korean general population aged 50 years or older. FINDINGS: The study population consisted of 8,857 subjects (3,545 men and 5,312 women) who participated in the baseline survey of the Dong-gu study, conducted in Korea between 2007 and 2010. Serum 25(OH)D and PTH concentrations were measured by chemiluminescent microparticle immunoassay. The optimal 25(OH)D concentration was estimated by using nonlinear regression model. Our data show that PTH concentration reached a theoretical plateau at 38.2 pg/ml and corresponding 25(OH)D concentration was 21.1 ng/ml in men and PTH concentration at 42.9 pg/ml and 25(OH)D concentration at 13.8 ng/ml in women. CONCLUSIONS: These results indicate that, for Korean general population aged 50 years or older, the optimal 25(OH)D concentration is 21.1 ng/ml in men and 13.8 ng/ml in women.

A high-fat diet containing lard accelerates prostate cancer progression and reduces survival rate in mice: possible contribution of adipose tissue-derived cytokines.

To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

Genetic variation in PSCA is associated with bladder cancer susceptibility in a Korean population.

BACKGROUND: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. MATERIALS AND METHODS: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. RESULTS: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT=1.58, 95% CI=1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. CONCLUSIONS: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.

Association between Apolipoprotein E Polymorphism and Chronic Kidney Disease in the Korean General Population: Dong-gu Study.

BACKGROUND: Few studies have investigated the association between Apolipoprotein E (APOE) polymorphisms and chronic kidney disease (CKD) in the general population, and their results are inconsistent. METHODS: The current study population was composed of 9,033 subjects aged ≥ 50 years who participated in the baseline survey of the Dong-gu Study, which was conducted in Korea between 2007 and 2010. APOE polymorphisms were identified by polymerase chain reaction, and the estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. RESULTS: Individuals with the APOE E2 allele had significantly lower total and low density lipoprotein cholesterol levels, those with the APOE E4 allele had lower high density lipoprotein (HDL) cholesterol levels, and those with the APOE E3 allele had lower log-triglyceride levels. Adjusting for covariates (sex, age, body mass index, smoking, systolic blood pressure, hypertension, diabetes, total cholesterol, HDL cholesterol, log-transformed triglycerides, and log-transformed albumin to creatinine ratio), mean eGFR was not significantly different among APOE alleles (E2, 69.4 mL/min/1.73 m(2); E3, 69.5 mL/min/1.73 m(2); E4, 69.4 ml/min/1.73 m(2); P = 0.873). Additionally, the odds ratios (ORs) indicated that APOE polymorphisms were not independent risk factors for CKD (OR, 1.07; 95% confidence interval [CI], 0.91 to 1.26 for the E2 vs. E3 allele; OR, 1.01; 95% CI, 0.88 to 1.16 for the E4 vs. E3 allele). CONCLUSION: APOE polymorphisms were not associated with either eGFR or CKD in the general Korean population.

Carnosic acid inhibits the epithelial-mesenchymal transition in B16F10 melanoma cells: a possible mechanism for the inhibition of cell migration.

Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 µmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration.

High prevalence of vitamin D deficiency in adults aged 50 years and older in Gwangju, Korea: the Dong-gu Study.

Vitamin D plays an important role in bone metabolism and maintaining bone health. Recently, new evidence has revealed that vitamin D affects chronic diseases such as autoimmune diseases, cardiovascular diseases and certain cancers. The aim of this study was to evaluate the vitamin D status and the prevalence of vitamin D deficiency in an urban Korean population. This study included 8,976 participants (3,587 men and 5,389 women) aged 50 yr and older. Serum 25(OH)D level was measured by chemiluminescent microparticle immunoassay. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] was 59.7% and 86.5% in men and women, respectively. The prevalence of vitamin D deficiency increased significantly with age in men, but not in women and it decreased from April to July, more prominently in men than in women. These results suggest that sun exposure, intake of vitamin D supplement, and regular physical activities is recommended in an urban Koreans, especially in women.

APOE polymorphism and carotid atherosclerosis in Korean population: the Dong-gu Study and the Namwon Study.

OBJECTIVE: We evaluated the association between APOE polymorphism and carotid atherosclerosis in two large independent cohorts from South Korea. METHODS: The datasets were from the Dong-gu Study (N = 9056) and the Namwon Study (N = 10,158). Carotid ultrasonography was performed to measure carotid intima-media thickness (IMT) and the presence of carotid plaques. The APOE polymorphism was determined by PCR-RFLP. We performed combined and separate analyses for the two datasets. RESULTS: In the combined analysis, individuals with E2E2 or E2E3 genotype had a lower common carotid IMT compared with individuals with E3E3 genotype (0.684 mm vs. 0.736 mm, p = 0.007; 0.718 mm vs. 0.736 mm, p < 0.001, respectively). This association was very slightly attenuated but remained statistically significant after adjustment for blood lipids (0.690 mm vs. 0.736 mm, p = 0.033; 0.725 mm vs. 0.736 mm, p = 0.005, respectively). Compared with individuals with E3E3 genotype, individuals with E2E3 genotype had lower risk for carotid plaque (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.75-0.93), while individuals with E3E4 genotype had a higher risk for carotid plaque (OR = 1.09, 95% CI = 1.00-1.20). After adjustment for blood lipids, ORs of E2E3 genotype for carotid plaque was slightly attenuated but remained significant (OR = 0.87 95% CI = 0.78-0.97), while OR of E3E4 genotype were slightly attenuated and not significant (OR = 1.08, 95% CI, 0.99-1.18). CONCLUSIONS: We found that APOE polymorphism is associated with carotid atherosclerosis and this association was partly mediated through blood lipid. Our results suggest that APOE polymorphism may influence atherosclerosis through non-lipid pathways.

The effect of an APOE polymorphism on cognitive function depends on age.

It remains controversial whether APOE E4 polymorphism is related to cognitive function in general population. We aimed to evaluate an association between the APOE E4 genotype and cognitive function, and whether this association may differ by age. Cognitive function was assessed using the Korean version of modified Mini-Mental State Examination (K-mMMSE) in 10,371 Koreans aged 45-74 years in Namwon City. According to the APOE E4 status, all participants were classified as non-carriers, heterozygotes, or homozygotes. Multiple linear and logistic regression models were used to evaluate the association between APOE genotypes and cognition. The frequency of APOE genotypes in the study population was 0.4, 10.1, 1.1, 72.9, 14.7 and 0.8 % for E2E2, E2E3, E2E4, E3E3, E3E4, and E4E4, respectively. Compared to the APOE E4 non-carriers, the heterozygotes and homozygotes showed 1.3 and 7.3 % lower K-mMMSE scores at 65-74 years and 0.8 and 4.6 % higher scores at 45-55 years, respectively. Educational attainment modified the effect of APOE E4 on cognitive function in the 45-54 age group (p for interaction =0.003), showing that the E4 carriers with no-formal education showed significantly higher cognitive function than those with formal education. The present study demonstrates that the effect of APOE E4 on cognitive function depends on age and education.

Common genetic variants at 1q22 and 10q23 and gastric cancer susceptibility in a Korean population.

Genetic variants at 1q22 and 10q23 were identified as genetic markers of both gastric cancer and esophageal squamous cell carcinoma susceptibility by two genome-wide association studies. The aim of this study was to determine whether rs4072037A > G in MUC1 at 1q22 and rs2274223A > G in PLCE1 at 10q23 are associated with a risk of gastric cancer in a Korean population. We conducted a large-scale case-control study of 3,245 patients with gastric cancer and 1,700 controls. The allele frequencies of rs4072037G and rs2274223G were 11.2 and 25.5% among patients with gastric cancer, compared with 12.8 and 26.4%, respectively, among controls. We found that the rs4072037 AG genotype was significantly associated with a reduced risk of gastric cancer [odds ratios (OR) = 0.78; 95% confidence interval (CI) = 0.67-0.91 for AG vs AA]. Compared with the rs2274223 AA genotype, we found a significant association between the rs2274223 AG genotype and a weakly reduced risk of gastric cancer (OR = 0.87; 95% CI = 0.76-0.99 for AG vs AA). Our data suggest that genetic variants at 1q22 and 10q23 play a role in gastric carcinogenesis.

Genetic variations in the PRKAA1 and ZBTB20 genes and gastric cancer susceptibility in a Korean population.

A recent genome-wide association study (GWAS) identified new susceptibility single-nucleotide polymorphisms (SNPs) rs13361707 (PRKAA1 and PTGER4 gene on 5p13.1) and rs9841504 (ZBTB20 gene on 3q13.31) that were significantly associated with non-cardia gastric cancer. The aim of this study was to determine whether rs13361707 and rs9841504 polymorphisms are associated with the risk of gastric cancer in a Korean population. We conducted a large-scale case-control study of 3245 gastric cancer patients and 1700 controls. The allele frequencies for rs13361707 C and rs9841504 G were 53.5% and 18.3% among gastric cancer cases, compared with 47.1% and 17.2% among controls, respectively. We found that rs13361707 TC and CC genotypes were associated with increased risk for gastric cancer (odds ratios [OR] = 1.29; 95% confidence interval [CI] = 1.11-1.51 for TC vs. TT and 1.68; 1.41-2.01 for CC vs. TT). However, we found no significant association between rs9841504 and gastric cancer risk (OR = 1.11; 0.97-1.28 for CG vs. CC; OR = 1.09; 0.77-1.53 for GG vs. CC). We observed no significant interactions between rs13361707 and rs9841504 polymorphisms and age, gender, smoking habit, alcohol consumption, and clinicopathologic characteristics such as anatomical tumor location and histological type. Our study showed that the rs13361707 polymorphism was associated with increased risk of gastric cancer in a Korean population. This finding provides further evidence that genetic variant of PRKAA1 and PTGER4 genes may contribute to the gastric carcinogenesis. However, we found no association between rs9841504 and gastric cancer risk.

Association between methylenetetrahydrofolate reductase C677T polymorphism and bone mineral density: the Dong-gu Study and the Namwon Study.

The purpose of this study was to examine the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and bone mineral density (BMD). Two large cohort studies were performed: the Dong-gu Study (3,621 men and 5,409 women) and the Namwon Study (3,703 men and 5,672 women). We assessed lumbar spine and femoral neck BMD by dual-energy X-ray absorptiometry. Genotypes were determined by real-time polymerase chain reaction. Multiple linear regression analysis was performed to evaluate the association between MTHFR C677T and BMD, adjusting for age, weight and height. The MTHFR C677T genotype frequencies for CC, CT, and TT genotypes were 34.5, 48.7, and 16.8%, respectively, in the Dong-gu Study and 33.6, 49.2, and 17.2%, respectively, in the Namwon Study. There are no significant differences between the MTHFR C677T genotype and the BMD at the lumbar spine and femoral neck in men or women in both cohorts.

Association of bone mineral density with albuminuria and estimated glomerular filtration rate: the Dong-gu Study.

BACKGROUND: Kidney dysfunction and albuminuria may be associated with BMD. However, little evidence has been reported on relationships between BMD and eGFR and albuminuria. METHODS: A total of 8,992 subjects aged 50 years or older participated in a survey conducted. Participants had their lumbar spine and femoral neck BMD measured by a Lunar Prodigy bone densitometer (GE, Madison, WI). Kidney function was assessed using MDRD eGFR and diagnosis of albuminuria was based on albumin-creatinine ratio. RESULTS: ACR was negatively associated with lumbar spine and femur neck BMD in females (lumbar spine: 1.001, 0.988, 0.974 and 0.979 g/cm(2), p < 0.001; femur neck: 0.796, 0.790, 0.783 and 0.782 g/cm(2), p = 0.002), but not in males, after adjusting for covariates. Additionally, eGFR was shown to be negatively associated with lumbar spine BMD after adjusting for covariates (male: 1.181, 1.166, 1.152 and 1.149 g/cm(2), p = 0.001; female: 0.997, 0.980, 0.979 and 0.982 g/cm(2), p = 0.005), but demonstrated no association with femur BMD. CONCLUSIONS: ACR in females was negatively associated with lumbar spine and femur neck BMD, but not in males. eGFR was negatively associated with lumbar spine BMD in both males and females.