Abstract:
:The circulating concentrations of triglycerides, high density lipoprotein (HDL)‑cholesterol, and low density lipoprotein (LDL)‑cholesterol have a substantial genetic component, and the heritability of early‑onset dyslipidemia might be expected to be higher compared with late‑onset forms. In the present study, exome‑wide association studies (EWASs) were performed for early‑onset hypertriglyceridemia, hypo‑HDL‑cholesterolemia, and hyper‑LDL‑cholesterolemia, with the aim to identify genetic variants that confer susceptibility to these conditions in the Japanese population. A total of 8,073 individuals aged ≤65 years were enrolled in the study. The EWASs for hypertriglyceridemia (2,664 cases and 5,294 controls), hypo‑HDL‑cholesterolemia (974 cases and 7,085 controls), and hyper‑LDL‑cholesterolemia (2,911 cases and 5,111 controls) were performed with Illumina Human Exome‑12 v1.2 DNA Analysis BeadChip or Infinium Exome‑24 v1.0 BeadChip arrays. The association of allele frequencies for 31,198, 31,133, or 31,175 single nucleotide polymorphisms (SNPs) to hypertriglyceridemia, hypo‑HDL‑cholesterolemia, or hyper‑LDL‑cholesterolemia, respectively, was examined with Fisher's exact test. To compensate for multiple comparisons of genotypes with each of the three conditions, Bonferroni's correction was applied for statistical significance of association. The results demonstrated that 25, 28 and 65 SNPs were significantly associated with hypertriglyceridemia, hypo‑HDL‑cholesterolemia and hyper‑LDL‑cholesterolemia, respectively. Multivariable logistic regression analysis with adjustment for age and sex revealed that all 25, 28 and 65 of these SNPs were significantly associated with hypertriglyceridemia, hypo‑HDL‑cholesterolemia and hyper‑LDL‑cholesterolemia, respectively. Following examination of the association of the identified SNPs to serum concentrations of triglycerides, HDL‑cholesterol, or LDL‑cholesterol, linkage disequilibrium of the SNPs, and results of previous genome‑wide association studies, we newly identified chromosomal region 19p12 as a susceptibility locus for hypertriglyceridemia, eight loci (MOB3C‑TMOD4, LPGAT1, EHD3, COL6A3, ZNF860‑CACNA1D, COL6A5, DCLRE1C, ZNF77) for hypo‑HDL‑cholesterolemia, and three loci (KIAA0319‑FAM65B, UBD, LOC105375015) for hyper‑LDL‑cholesterolemia. The present study thus identified 12 novel loci that may confer susceptibility to early‑onset dyslipidemia. Determination of genotypes for the SNPs at these loci may prove informative for assessment of genetic risk for hypertriglyceridemia, hypo‑HDL‑cholesterolemia, or hyper‑LDL‑cholesterolemia in the Japanese population.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Yamada Y,Kato K,Oguri M,Horibe H,Fujimaki T,Yasukochi Y,Takeuchi I,Sakuma Jdoi
10.3892/ijmm.2018.3943subject
Has Abstractpub_date
2019-01-01 00:00:00pages
57-82issue
1eissn
1107-3756issn
1791-244Xjournal_volume
43pub_type
杂志文章abstract::The number of patients suffering from diabetes mellitus is constantly rising worldwide, and diabetic retinopathy (DR) has become the most frequent cause of postnatal blindness. Vascular endothelial growth factor (VEGF) is known to play a central role during DR development. Thus, inhibiting the effects of VEGF may hamp...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::The antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) is implicated in migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of Trolox on metastatic cancer cells is not known. We found that a non-cytotoxic dose ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.832
更新日期:2012-02-01 00:00:00
abstract::The pathologic mechanisms of pulmonary fibrosis (PF), one of the most common chronic pulmonary diseases, remain unclear. Napsin A is an aspartic proteinase that has been regarded as a hallmark of pulmonary adenocarcinoma. The present study aimed to investigate the specific function and molecular mechanisms of Napsin A ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2020.4565
更新日期:2020-07-01 00:00:00
abstract::Rosiglitazone has been found to have anti-atherogenic effects and to increase serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels. However, in vivo studies investigating the regulation of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) by rosigli...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2072
更新日期:2015-03-01 00:00:00
abstract::Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, photosensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS. The BLM protein is homologous to DNA helicase and has two basic amino acid clusters in its C-termina...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.5.5.477
更新日期:2000-05-01 00:00:00
abstract::Whether or not nutritionally-regulated foreign gene expression in vivo is achievable was examined in mouse liver after in vivo gene transfer by electroporation (EP). Electric pulses were applied to a left liver lobe immediately after injection of a luciferase reporter gene driven by the liver-type phosphoenolpyruvate ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.7.1.61
更新日期:2001-01-01 00:00:00
abstract::High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated C...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract::The underground parts of Nardostachys chinensis (N. chinensis), which belongs the genus Valerianaceae, have been used as sedative and analgesic agents in traditional Korean medicine for centuries. The mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1596
更新日期:2014-03-01 00:00:00
abstract::Induction of apoptosis is one of the mechanisms of chemotherapeutic agents against breast cancer. In addition, recent studies have shown that diets containing polyphenolic components possess anticancer activities either in vitro or in vivo by inhibiting cell proliferation and inducing apoptosis. The aim of our study w...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2010-07-01 00:00:00
abstract::Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is found to be overexpressed in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the possible role of GPC3 in the development of HCC. In this study, RNA interference (RNAi) with a GPC3 small hairpin RNA (GPC3 shRNA) wa...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.704
更新日期:2011-10-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key element in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Moreover, it is a negative regulator of autophagy and acts as a central regulator in cell growth. For the treatment of cancer, mTOR is a nove...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1282
更新日期:2013-04-01 00:00:00
abstract::A microarray analysis of an animal model with experimental sepsis induced by caecal ligation and puncture revealed that the level of microRNA‑195 (miR‑195) was upregulated. However, to the best of our knowledge, the role of miR‑195 in sepsis remains unknown. The present study investigated the effect of miR‑195 on apop...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4431
更新日期:2020-02-01 00:00:00
abstract::Atherosclerosis is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in its occurrence and development. Simvastatin is a lipid‑lowering drug, which is commonly used to prevent or treat risk factors of cardiovascular diseases with a significant ant...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4310
更新日期:2019-10-01 00:00:00
abstract::The aim of the present study was to examine the protective effect of caveolin‑1 (Cav‑1) in the penehyclidine hydrochloride (PHC)‑based inhibition of lipopolysaccharide (LPS)‑induced acute lung injury (ALI) in vivo and in vitro, in addition to the potential underlying mechanisms. In vivo, an ALI rat model was establish...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4117
更新日期:2019-05-01 00:00:00
abstract::The kallikrein-kinin system (KKS) is a complex multi-enzyme system which is composed of circulating and tissue kallikrein and kinin. It is well established that tissue kallikrein and kinin play crucial and diverse roles in cardiovascular and renal homeostasis. Recent data indicate t...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2012.922
更新日期:2012-05-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats we...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3607
更新日期:2018-07-01 00:00:00
abstract::Akt1/protein kinase Bα (Akt1/PKBα) is a downstream mediator of the insulin signaling system. In this study we explored mechanism(s) for its role in burn injury. Akt1/PKBα in liver extracts from mice with burn injury fed with (2H7)-L-Leu was immunoprecipitated and isolated with SDS-PAGE. Two tryptic peptides, one in th...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.861
更新日期:2012-03-01 00:00:00
abstract::Glucosamine, a naturally occurring amino monosaccharide, is widely used to treat osteoarthritis in humans. Furthermore, glucosamine exhibits an anti-inflammatory action by inhibiting the activation of neutrophils, chondrocytes and synoviocytes. Recently, we revealed that glucosamine suppresses cytokine-induced activat...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2008-09-01 00:00:00
abstract::Excessive preadipocyte differentiation/adipogenesis is closely linked to the development of obesity. LY3009120 is a pan‑Raf kinase inhibitor and is known for its anticancer activities. In the present study, the effect of LY3009120 on 3T3‑L1 cell adipogenesis was investigated. The differentiation of 3T3‑L1 preadipocyte...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3890
更新日期:2018-12-01 00:00:00
abstract::The thymus is the primary site for T-cell lympho-poiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pat...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1709
更新日期:2014-06-01 00:00:00
abstract::Breast cancer accounts for 30-40% of all deaths from cancers in females. In an effort to identify tumor associated antigens that may be useful for immunotherapy, we utilized serological analysis of recombinant cDNA expression libraries (SEREX) technique to identify breast cancer-associated antigens. SEREX screening of...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract::Electrical activity of beta-cells and cytosolic Ca2+ concentration ([Ca2+]i) were monitored in mouse pancreatic islets exposed to the pentaacetate esters of alpha-D-glucose, beta-D-galactose and beta-L-glucose, all tested at 1.7 mM concentration. In the presence of 5 mM D-glucose, alpha-D-glucose pentaacetate induced ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.3.1.15
更新日期:1999-01-01 00:00:00
abstract::Dextromethorphan is a widely used anti-tussive drug with non-competitive antagonistic effects on excitatory amino acid receptors of the N-methyl-D-aspartate (NMDA) type. This study examined the effect of daily dextromethorphan administration on gene expression in rat brain hippocampus and cortex regions using Rat 5K c...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Congenital bicuspid aortic valve (BAV) represents the most common type of cardiac birth defect affecting 0.4‑2% of the general population, and accounts for a markedly increased incidence of life‑threatening complications, including valvulopathy and aortopathy. Accumulating evidence has demonstrated the genetic basis o...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4087
更新日期:2019-04-01 00:00:00
abstract::Aquaporins (AQPs) have been found to be associated with a number of diseases. However, the role of AQP‑1 in the pathogenesis of osteoarthritis remains unclear. We previously found that AQP‑1 expression was upregulated in osteoarthritic cartilage and strongly correlated with caspase‑3 expression and activity. The aim o...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2785
更新日期:2016-12-01 00:00:00
abstract::The interaction between prostate cancer cells and bone marrow stromal cells (BMSC) is critical for survival and proliferation of metastatic cancer cells in the bone microenvironment. In order to study molecular mechanisms of prostate cancer bone metastasis, we established a novel heterotypic co-culture system, in whic...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract::The tree shrew (Tupaia belangeri) diverges from the primate order (Primates) and is classified as a separate taxonomic group of mammals - Scandentia. It has been suggested that the tree shrew can be used as an animal model for studying human diseases; however, the genomic sequence of the tree shrew is largely unidenti...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2040
更新日期:2015-02-01 00:00:00
abstract::Histone deacetylase inhibitor (HDAI) induces accumulation of highly acetylated histones by inhibiting the activity of histone deacetylase and inhibits cell proliferation, induces differentiation, and promotes apoptosis. TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis in various human cancer cells, a pr...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract::Mammalian cardiomyocytes may permanently lose their ability to proliferate after birth. Therefore, studying the proliferation and growth arrest of cardiomyocytes during the postnatal period may enhance the current understanding regarding this molecular mechanism. The present study identified the differentially express...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3234
更新日期:2018-01-01 00:00:00
abstract::For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were u...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.4.2.203
更新日期:1999-08-01 00:00:00