Endocrinology and metabolism (Seoul, Korea)最新文献

{"title":"Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway.","authors":"Jinmi Lee,&nbsp;Seok-Woo Hong,&nbsp;Min-Jeong Kim,&nbsp;Sun Joon Moon,&nbsp;Hyemi Kwon,&nbsp;Se Eun Park,&nbsp;Eun-Jung Rhee,&nbsp;Won-Young Lee","doi":"10.3803/EnM.2021.1293","DOIUrl":"https://doi.org/10.3803/EnM.2021.1293","url":null,"abstract":"<p><strong>Background: </strong>Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA).</p><p><strong>Methods: </strong>HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting.</p><p><strong>Results: </strong>Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation.</p><p><strong>Conclusion: </strong>These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"74-83"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/aa/enm-2021-1293.PMC8901965.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal Morphology as an Indicator of Long-Term Disease Control in Adults with Classic 21-Hydroxylase Deficiency.","authors":"Taek Min Kim,&nbsp;Jung Hee Kim,&nbsp;Han Na Jang,&nbsp;Man Ho Choi,&nbsp;Jeong Yeon Cho,&nbsp;Sang Youn Kim","doi":"10.3803/EnM.2021.1278","DOIUrl":"https://doi.org/10.3803/EnM.2021.1278","url":null,"abstract":"Background Monitoring adults with classical 21-hydroxylase deficiency (21OHD) is challenging due to variation in clinical and laboratory settings. Moreover, guidelines for adrenal imaging in 21OHD are not yet available. We evaluated the relationship between adrenal morphology and disease control status in classical 21OHD. Methods This retrospective, cross-sectional study included 90 adult 21OHD patients and 270 age- and sex-matched healthy controls. We assessed adrenal volume, width, and tumor presence using abdominal computed tomography and evaluated correlations of adrenal volume and width with hormonal status. We investigated the diagnostic performance of adrenal volume and width for identifying well-controlled status in 21OHD patients (17α-hydroxyprogesterone [17-OHP] <10 ng/mL). Results The adrenal morphology of 21OHD patients showed hypertrophy (45.6%), normal size (42.2%), and hypotrophy (12.2%). Adrenal tumors were detected in 12 patients (13.3%). The adrenal volume and width of 21OHD patients were significantly larger than those of controls (18.2±12.2 mL vs. 7.1±2.0 mL, 4.7±1.9 mm vs. 3.3±0.5 mm, P<0.001 for both). The 17-OHP and androstenedione levels were highest in patients with adrenal hypertrophy, followed by those with normal adrenal glands and adrenal hypotrophy (P<0.05 for both). Adrenal volume and width correlated positively with adrenocorticotropic hormone, 17-OHP, 11β-hydroxytestosterone, progesterone sulfate, and dehydroepiandrosterone sulfate in both sexes (r=0.33–0.95, P<0.05 for all). For identifying well-controlled patients, the optimal cut-off values of adrenal volume and width were 10.7 mL and 4 mm, respectively (area under the curve, 0.82–0.88; P<0.001 for both). Conclusion Adrenal volume and width may be reliable quantitative parameters for monitoring patients with classical 21OHD.","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"124-137"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/61/enm-2021-1278.PMC8901969.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Repositioning Using Temporal Trajectories of Accompanying Comorbidities in Diabetes Mellitus.","authors":"Namgi Park,&nbsp;Ja Young Jeon,&nbsp;Eugene Jeong,&nbsp;Soyeon Kim,&nbsp;Dukyong Yoon","doi":"10.3803/EnM.2021.1275","DOIUrl":"https://doi.org/10.3803/EnM.2021.1275","url":null,"abstract":"<p><strong>Background: </strong>Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates' effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications.</p><p><strong>Methods: </strong>Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records.</p><p><strong>Results: </strong>We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44).</p><p><strong>Conclusion: </strong>To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"65-73"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/ce/enm-2021-1275.PMC8901955.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Outcomes with Finerenone According to Glycemic Status at Baseline and Prior Treatment with Newer Antidiabetics among Patients with Type 2 Diabetes Mellitus.","authors":"Dimitrios Patoulias,&nbsp;Christodoulos Papadopoulos,&nbsp;Asterios Karagiannis,&nbsp;Vassilios Vassilikos,&nbsp;Michael Doumas","doi":"10.3803/EnM.2021.1296","DOIUrl":"https://doi.org/10.3803/EnM.2021.1296","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) and cardiovascular disease are closely interconnected. We sought to determine the cardioprotective action of finerenone according to prior treatment with newer antidiabetics and glycemic status. We searched PubMed and Cochrane Library from inception to October 1, 2021 for randomized controlled trials (RCTs) assessing the effect of finerenone on major adverse cardiovascular outcomes in patients with T2DM. We set the primary endpoint as major adverse cardiovascular events (MACE), defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. We finally included two RCTs in our quantitative synthesis. Compared to placebo, finerenone induced a 23% risk reduction for the composite cardiovascular endpoint, regardless of prior glycemia. We also showed that finerenone provided significant cardiovascular benefit for obese patients with T2DM compared to placebo, although this benefit was diminished for subjects with a body mass index lower than 30 kg/m2. Finally, the combination of finerenone with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists did not produce a significant risk reduction for MACE. We conclude that finerenone provides significant cardiovascular benefits for patients with T2DM, especially for those who are obese, while glycemic status or treatment with newer antidiabetics at baseline does not affect the observed cardioprotective action.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"170-174"},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/d9/enm-2021-1296.PMC8901958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal Neuroma Cues for Endocrine Emergency Treatment.","authors":"Gyu Gang Choi,&nbsp;Hwan Jin Lee,&nbsp;Hyo Jin Han,&nbsp;Young Beom Jeong,&nbsp;Heung Bum Lee,&nbsp;Ji Hyun Park","doi":"10.3803/EnM.2021.1269","DOIUrl":"https://doi.org/10.3803/EnM.2021.1269","url":null,"abstract":"Corresponding author: Ji Hyun Park Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea Tel: +82-63-250-1780, Fax: +82-63-254-1609, E-mail: parkjh@jbnu.ac.kr Copyright © 2021 Korean Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/ licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Mucosal Neuroma Cues for Endocrine Emergency Treatment","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"1312-1313"},"PeriodicalIF":3.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/89/d5/enm-2021-1269.PMC8743591.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39685554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes and Hyperthyroidism: Is There a Causal Link?","authors":"Sang Yong Kim","doi":"10.3803/EnM.2021.602","DOIUrl":"https://doi.org/10.3803/EnM.2021.602","url":null,"abstract":"Diabetes mellitus (DM) and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. It is well known that Hashimoto’s thyroiditis and Graves’ disease are autoimmune disorders that constitute the most prevalent forms of TD [1]. It is also known that type 1 DM occurs due to autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency [2]. The combination of these types of TD and type 1 DM, as autoimmune-induced endocrine disorders, is termed polyglandular autoimmune syndrome [3]. Beyond these relationships between autoimmune-induced endocrine disorders, several studies have demonstrated that TD is closely related to DM. TD is more common in patients with type 2 DM than in the general population and can adversely influence their metabolic control. The overall prevalence of TD in patients with type 2 DM in several countries has been reported to range from 4% to 20% [4,5]. It is well known that both hyperthyroidism and hypothyroidism can change glucose and lipid metabolism. Metabolic changes in patients with hyperthyroidism mainly result from increased insulin resistance, because excess thyroid hormone increases endogenous glucose production and insulin requirements and reduces hepatic insulin sensitivity [6]. Therefore, when hyperthyroidism occurs in patients with DM, they are at an elevated risk of severe hyperglycemia and poor glycemic control. However, although the association between hyperthyroidism and glucose metabolism is well documented, few studies have prospectively investigated the relationship between TD and new-onset DM. Moreover, the studies that have addressed this issue have predominantly investigated the relationship between hypothyroidism and the incidence of DM [7,8]. In this respect, it is necessary to investigate the risk of DM in patients with hyperthyroidism and to establish a screening program accordingly. In this issue of Endocrinology and Metabolism, Song et al. [9] published a study investigating the risk of DM in patients with long-standing Graves’ disease using retrospective data from the Korean National Health Insurance Service database. Long-standing Graves’ disease was defined as anti-thyroid drug (ATD) treatment for more than 24 months after the diagnosis of hyperthyroidism. The patients were also subclassified into a group that maintained ATD for more than 12 months after initial treatment for 24 months and a group that received radioactive iodine ablation (RIA) therapy after initial treatment. The authors reported that the hazard ratio for DM occurrence was 1.18 in patients with hyperthyroidism after adjustment compared to the control group. The risk of DM increased with an increased duration of ATD treatment, as well as in the RIA therapy group. From these results, we can infer that hyperthyroidism increases the incidence of DM by causing changes in blood glucose metabolism, especially in patients receiving long-term ATD therapy or RAI therapy. Notably, the ","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"1175-1177"},"PeriodicalIF":3.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/e1/enm-2021-602.PMC8743583.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39786588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea.","authors":"Yeon-Hee Baek,&nbsp;Sun Wook Cho,&nbsp;Han Eol Jeong,&nbsp;Ju Hwan Kim,&nbsp;Yunji Hwang,&nbsp;Jeffrey L Lange,&nbsp;Ju-Young Shin","doi":"10.3803/EnM.2021.1215","DOIUrl":"https://doi.org/10.3803/EnM.2021.1215","url":null,"abstract":"<p><strong>Background: </strong>In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.</p><p><strong>Methods: </strong>BMD was classified as normal (T-score ≥-1.0 standard deviation [SD]), osteopenia (T-score <-1.0 SD and >-2.5 SD), and osteoporosis (T score ≤-2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.</p><p><strong>Results: </strong>Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.</p><p><strong>Conclusion: </strong>Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"1178-1188"},"PeriodicalIF":3.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/ef/enm-2021-1215.PMC8743593.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39844141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE-/-FXR-/- Mice.","authors":"Yenna Lee,&nbsp;Bo-Rahm Kim,&nbsp;Geun-Hyung Kang,&nbsp;Gwan Jae Lee,&nbsp;Young Joo Park,&nbsp;Haeryoung Kim,&nbsp;Hak Chul Jang,&nbsp;Sung Hee Choi","doi":"10.3803/EnM.2021.1100","DOIUrl":"https://doi.org/10.3803/EnM.2021.1100","url":null,"abstract":"<p><strong>Background: </strong>Farnesoid X receptor (FXR), a bile acid-activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.</p><p><strong>Methods: </strong>En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)-/- and ApoE-/-FXR-/- mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.</p><p><strong>Results: </strong>Compared with ApoE-/- mice, ApoE-/-FXR-/- mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE-/-FXR-/- mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).</p><p><strong>Conclusion: </strong>Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"1243-1253"},"PeriodicalIF":3.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/50/enm-2021-1100.PMC8743579.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39786589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study.","authors":"Ye An Kim,&nbsp;Ji Won Yoon,&nbsp;Young Lee,&nbsp;Hyuk Jin Choi,&nbsp;Jae Won Yun,&nbsp;Eunsin Bae,&nbsp;Seung-Hyun Kwon,&nbsp;So Eun Ahn,&nbsp;Ah-Ra Do,&nbsp;Heejin Jin,&nbsp;Sungho Won,&nbsp;Do Joon Park,&nbsp;Chan Soo Shin,&nbsp;Je Hyun Seo","doi":"10.3803/EnM.2021.1241","DOIUrl":"https://doi.org/10.3803/EnM.2021.1241","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).</p><p><strong>Methods: </strong>We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.</p><p><strong>Results: </strong>rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.</p><p><strong>Conclusion: </strong>The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"1189-1200"},"PeriodicalIF":3.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/ab/enm-2021-1241.PMC8743587.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39950417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment.","authors":"Eunhee Jang,&nbsp;Jeonghoon Ha,&nbsp;Ki-Hyun Baek,&nbsp;Moo Il Kang","doi":"10.3803/EnM.2021.1248","DOIUrl":"https://doi.org/10.3803/EnM.2021.1248","url":null,"abstract":"<p><strong>Background: </strong>Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.</p><p><strong>Methods: </strong>We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.</p><p><strong>Results: </strong>After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (-11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).</p><p><strong>Conclusion: </strong>Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"1211-1218"},"PeriodicalIF":3.4,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/0c/enm-2021-1248.PMC8743595.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39953983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}