Abstract:
BACKGROUND:DNA methylation at specific CpG sites within gene promoter regions is known to regulate transcriptional activity in vitro. In human adipose tissue, basal transcription of the aromatase (CYP19A1) gene is driven primarily by the I.4 promoter however the role of DNA methylation in regulating expression in ex vivo mature adipocytes is unknown. This observational study reports the correlation of DNA methylation within the I.4 promoter region of human mature subcutaneous and omental adipocytes with aromatase expression and body composition measures. METHODS:Omental and subcutaneous adipose tissue were collected from 25 obese subjects undergoing bariatric surgery and the mature adipocyte fraction purified. DNA methylation status of 5 CpG sites within a 550 base pair region encompassing the transcription start site (TSS) of promoter I.4 was determined using pyrosequencing. Relative aromatase and I.4 promoter specific mRNA expression was determined by qRT-PCR and whole body DXA performed in 25 participants. RESULTS:Site-specific DNA methylation varied from 21 ± 10% to 81 ± 11%. In omental adipocytes percentage methylation at the I.4.1 and I.4.2 CpG sites, but not other nearby sites, was negatively correlated with relative aromatase mRNA expression (R = - 0.52, P = 0.017 and R = - 0.52, P = 0.015). In contrast subcutaneous adipocytes percentage DNA methylation at the I.4.3 and I.4.5 sites were positively correlated with relative aromatase mRNA expression (R = 0.47, P = 0.022 and R = 0.55, P = 0.004). In a small subset of patients DNA methylation at the I.4.5 site was also positively correlated with whole body lean mass, bone mineral content and density. CONCLUSIONS:In conclusion in mature adipocytes, the primary source of estradiol after menopause, increasing DNA methylation was correlated with aromatase mRNA expression and thus estradiol biosynthesis. These findings support a tissue-specific epigenetic regulation of the basal promoter activity in mature adipocytes; the mechanisms influencing this regulation and its physiological role remain to be elucidated.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Lewis JR,McNab TJ,Liew LJ,Tan J,Hudson P,Wang JZ,Prince RLdoi
10.1186/1471-2350-14-87subject
Has Abstractpub_date
2013-08-30 00:00:00pages
87issn
1471-2350pii
1471-2350-14-87journal_volume
14pub_type
杂志文章abstract:BACKGROUND:Amyloidoses are a heterogeneous group of progressive diseases caused by tissue deposition of misfolded proteins. According to the International Classification of Diseases, hereditary amyloidosis is divided into neuropathic and non-neuropathic forms. In Sweden, neuropathic heredofamilial amyloidosis has been ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-88
更新日期:2013-09-03 00:00:00
abstract:BACKGROUND:Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-67
更新日期:2007-11-09 00:00:00
abstract:BACKGROUND:The presence of the Y-chromosome or Y chromosome-derived material is seen in 4-60% of Turner syndrome patients (Chromosomal Disorders of Sex Development (DSD)). DSD patients with specific Y-chromosomal material in their karyotype, the GonadoBlastoma on the Y-chromosome (GBY) region, have an increased risk of...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-108
更新日期:2012-11-16 00:00:00
abstract:BACKGROUND:Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian po...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-123
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Congenital NBCe1A deficiency with the SLC4A4 mutation causes severe proximal renal tubular acidosis, which often comprises extrarenal symptoms, such as intellectual disability and developmental delay, glaucoma, cataract and band keratopathy. To date, almost all mutations have been found to be homozygous muta...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0612-y
更新日期:2018-06-18 00:00:00
abstract:BACKGROUND:I/D polymorphisms of ACE are associated with the plasma ACE concentration. The ACE is associated with the angiogenesis of ovarian endothelium in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE induces a high blood supply and hypersteroidogenesis in the ovary, it may be associated ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-64
更新日期:2009-07-14 00:00:00
abstract:BACKGROUND:The complement component (3b/4b) receptor 1 gene (CR1) gene has been proved to affect the susceptibility of Alzheimer's disease (AD) in different ethnic and districts groups. However, the effect of CR1 genetic variants on amyloid β (Aβ) metabolism of AD human is still unclear. Hence, the aim of this study wa...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01114-x
更新日期:2020-09-12 00:00:00
abstract:BACKGROUND:Congenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire AVPR2 locus and...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-42
更新日期:2008-05-20 00:00:00
abstract:BACKGROUND:Pulmonary capillary hemangiomatosis (PCH) is an uncommon pulmonary disorder, with variable clinical features depending on which lung structure is affected, and it is usually linked to pulmonary arterial hypertension. Congenital PCH has been very rarely described and, so far, the only causative gene identifie...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-015-0241-7
更新日期:2015-10-13 00:00:00
abstract:BACKGROUND:Rubinstein-Taybi syndrome (RSTS; OMIM #180849, #613684) is a rare autosomal dominant genetic condition characterized by broad thumbs and halluces, facial dysmorphism, short stature and variable degree of intellectual disability. RSTS is associated with mutations in CREBBP and EP300 genes in 50-60% and 5-8% o...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0361-8
更新日期:2016-12-13 00:00:00
abstract:BACKGROUND:We explored the association of leucine-rich repeats and calponin homology domain containing 1 (LRCH1) gene polymorphisms with genetic susceptibility to delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), which might provide a theoretical basis for the pathogenesis, diagnosis, and prognosis...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0931-7
更新日期:2019-12-16 00:00:00
abstract:BACKGROUND:Bone morphogenetic protein 4 gene (BMP4) plays a key role during maxillofacial development, since orofacial clefts are observed in animals when this gene is conditionally inactivated. We recently reported the existence of association between nonsyndromic cleft lip/palate (NSCLP) and BMP4 polymorphisms by det...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-12-163
更新日期:2011-12-19 00:00:00
abstract:BACKGROUND:Some Hirschsprung's disease (HSCR) patients showed persistent bowel symptoms following an appropriately performed pull-through procedure. The mechanism is presumed to be down-regulated small-conductance calcium-activated potassium channel 3 (SK3) expression in the HSCR ganglionic intestines. We aimed to inve...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0539-3
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Epidemiological studies have suggested that variants on adiponectin (ADIPOQ) and its receptor ADIPOR1 (adiponectin receptor 1) are associated with colorectal cancer (CRC) risk; however, the results were inconclusive. The aim of the study was to evaluate the associations between the variants on ADIPOQ and ADI...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-014-0137-y
更新日期:2014-12-17 00:00:00
abstract:BACKGROUND:Congenital nystagmus (CN) and congenital cataracts are distinct eye diseases and are usually isolated. Cases with CN and congenital cataracts caused by different genes in one family have been rarely reported. CASE PRESENTATION:A 27-year-old man presented with CN and congenital cataracts and he underwent cat...
journal_title:BMC medical genetics
pub_type: 杂志文章,评审
doi:10.1186/s12881-019-0780-4
更新日期:2019-03-19 00:00:00
abstract:BACKGROUND:Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-2-7
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Int22h1/int22h2-mediated Xq28 duplication syndrome is caused by ~0.5 Mb chromosomal duplications mediated by nonallelic homologous recombination between intron 22 homologous region 1 (int22h1) and 2 (int22h2), which, in addition to int22h3, are also responsible for inversions disrupting the F8 gene in hemoph...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-015-0157-2
更新日期:2015-03-14 00:00:00
abstract:BACKGROUND:Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-30
更新日期:2012-04-27 00:00:00
abstract:BACKGROUND:Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primari...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-7-41
更新日期:2006-04-28 00:00:00
abstract:BACKGROUND:Mutations in GATA6 are the most frequent cause of pancreatic agenesis. Most cases present with neonatal diabetes mellitus. CASE PRESENTATION:The case was a female born after an uncomplicated pregnancy and delivery in a non-consanguineous family (3.59 kg, 70th percentile). Severe cardiac malformations were d...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01012-2
更新日期:2020-04-03 00:00:00
abstract:BACKGROUND:Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-53
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND:Catechol-O-methyltransferase (COMT Val158Met) has been implicated in both depression and cardiovascular disease. The purpose of this study was to assess if COMT Val158Met, which influences the COMT enzyme activity, has an effect on the risk of cardiovascular disease (CVD) in individuals with a history of dep...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0645-2
更新日期:2018-07-25 00:00:00
abstract:BACKGROUND:Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, N-acetyltransferase 8 (NAT8) expressed in embryonic and adult kidney and associ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-25
更新日期:2008-04-10 00:00:00
abstract:BACKGROUND:Hereditary spherocytosis (HS) is a common type of hereditary hemolytic anemia. According to the current diagnostic criteria of HS, patients with a family history of HS, typical clinical features and laboratory investigations could be diagnosed without the requirement of any additional tests, including geneti...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0826-7
更新日期:2019-05-24 00:00:00
abstract:BACKGROUND:Neurofibromatosis type-1 (NF1) is caused by mutations of the NF1 gene at 17q11.2. In 95% of non-founder NF1 patients, NF1 mutations are identifiable by means of a comprehensive mutation analysis. 5-10% of these patients harbour microdeletions encompassing the NF1 gene and its flanking regions. NF1 is charact...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-98
更新日期:2012-10-26 00:00:00
abstract:BACKGROUND:CHARGE syndrome is characterized by coloboma, heart defects, choanal atresia, growth retardation, genitourinary malformation and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is the major cause of CHARGE syndrome and is inherited in an autosomal dominant manner. Currently, th...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0813-z
更新日期:2019-05-30 00:00:00
abstract:BACKGROUND:Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral den...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-112
更新日期:2008-12-17 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been pre...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-63
更新日期:2008-07-07 00:00:00
abstract:BACKGROUND:Cerebral folate deficiency (CFD) is a neurological disease, hallmarked by remarkable low concentrations of 5-methyltetrahydrofolic acid (5-MTHF) in cerebrospinal fluid (CSF). The primary causes of CFD include the presence of folate receptor (FR) autoantibodies, defects of FR encoding gene FOLR1, mitochondria...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01162-3
更新日期:2020-11-26 00:00:00
abstract:BACKGROUND:Mutations of EFNB1 cause the X-linked malformation syndrome craniofrontonasal syndrome (CFNS). CFNS is characterized by an unusual phenotypic pattern of inheritance, because it affects heterozygous females more severely than hemizygous males. This sex-dependent inheritance has been explained by random X-inac...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-98
更新日期:2010-06-17 00:00:00