Genetic and epigenetic mechanisms combine to control MMP1 expression and its association with preterm premature rupture of membranes.


:Degradation of fibrillar collagens is believed to be involved in the rupture of the fetal membranes during normal parturition and when the membranes rupture prematurely. Matrix metalloproteinase 1 (MMP1) is a key enzyme involved in extracellular matrix turnover, and genetic variation in the MMP1 promoter is associated with the risk of preterm premature rupture of membranes (PPROM). We determined whether epigenetic factors contribute to the control of MMP1 expression in the human amnion. Inhibition of DNA methylation with 5-aza-2'-deoxycytidine in amnion fibroblasts resulted in significantly increased MMP1 gene transcription, and an associated significant increase in MMP1 production. These effects were correlated with reduced DNA methylation at a particular site (-1538) in the MMP1 promoter. DNA methylation at this site in amnion was reduced in a larger percentage of fetal membranes that ruptured prematurely. A new T > C single nucleotide polymorphism (SNP) [AF007878.1 (MMP1):g.3447T>C] in the MMP1 promoter was also identified. The minor C allele was always methylated in vivo, and when methylated, resulted in increased affinity for a nuclear protein in amnion fibroblasts. The minor C allele had reduced promoter activity as assessed by plasmid transfection studies and chromatin immunoprecipitation assays using amnion fibroblasts heterozygous for the T > C SNP. In a case-control study, the minor C allele was found to be protective against PPROM, consistent with its reduced promoter function. We conclude that in addition to genetic variation, DNA methylation plays a role in controlling MMP1 expression and risk of an adverse obstetrical outcome.


Hum Mol Genet


Human molecular genetics


Wang H,Ogawa M,Wood JR,Bartolomei MS,Sammel MD,Kusanovic JP,Walsh SW,Romero R,Strauss JF 3rd




Has Abstract


2008-04-15 00:00:00














  • Utrophin A is essential in mediating the functional adaptations of mdx mouse muscle following chronic AMPK activation.

    abstract::Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin along muscle fibers. An attractive therapeutic avenue for DMD consists in the upregulation of utrophin A, a protein with high sequence identity and functional redundancy with dystrophin. Recent work has shown that pharmacological interventions th...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Al-Rewashdy H,Ljubicic V,Lin W,Renaud JM,Jasmin BJ

    更新日期:2015-03-01 00:00:00

  • Population differences in haplotype structure within a human olfactory receptor gene cluster.

    abstract::We investigated the population differences in patterns of single nucleotide polymorphisms (SNPs) for a 400 kb olfactory receptor (OR) gene cluster on human chromosome 17p13.3. Samples were drawn from 35 individuals, of four different ethnogeographical origins: Pygmies, Bedouins, Yemenite Jews and Ashkenazi Jews. Of th...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Menashe I,Man O,Lancet D,Gilad Y

    更新日期:2002-06-01 00:00:00

  • Allelic imbalance in BRCA1 and BRCA2 gene expression is associated with an increased breast cancer risk.

    abstract::The contribution of BRCA1 and BRCA2 to familial and non-familial forms of breast cancer has been difficult to accurately estimate because of the myriad of potential genetic and epigenetic mechanisms that can ultimately influence their expression and involvement in cellular activities. As one of these potential mechani...

    journal_title:Human molecular genetics

    pub_type: 临床试验,杂志文章


    authors: Chen X,Weaver J,Bove BA,Vanderveer LA,Weil SC,Miron A,Daly MB,Godwin AK

    更新日期:2008-05-01 00:00:00

  • Defining haplotype blocks and tag single-nucleotide polymorphisms in the human genome.

    abstract::Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Schulze TG,Zhang K,Chen YS,Akula N,Sun F,McMahon FJ

    更新日期:2004-02-01 00:00:00

  • CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.

    abstract::Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used t...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Benson KF,Horwitz M,Wolff J,Friend K,Thompson E,White S,Richards RI,Raskind WH,Bird TD

    更新日期:1998-10-01 00:00:00

  • A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human.

    abstract::A new gene, designated Smcx, was cloned from the mouse X chromosome by its homology to the Y located gene Smcy. Using direct in situ hybridisation Smcx was mapped to the distal end of the mouse X chromosome (XF2-XF4) and its human homologue, SMCX, was mapped to proximal Xp (Xp11.1-Xp11.2). Further meiotic mapping in t...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Agulnik AI,Mitchell MJ,Mattei MG,Borsani G,Avner PA,Lerner JL,Bishop CE

    更新日期:1994-06-01 00:00:00

  • Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice.

    abstract::Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ye M,Coldren C,Liang X,Mattina T,Goldmuntz E,Benson DW,Ivy D,Perryman MB,Garrett-Sinha LA,Grossfeld P

    更新日期:2010-02-15 00:00:00

  • Huntingtin-associated protein 1 (Hap1) mutant mice bypassing the early postnatal lethality are neuroanatomically normal and fertile but display growth retardation.

    abstract::Huntingtin-associated protein 1 (Hap1) is the first huntingtin interacting protein identified in a yeast two-hybrid screen. Although Hap1 expression has been demonstrated in neuronal and non-neuronal tissues, its molecular role is poorly understood. Recently, it has been shown that targeted disruption of Hap1 in mice ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Dragatsis I,Zeitlin S,Dietrich P

    更新日期:2004-12-15 00:00:00

  • Nucleolar stress and impaired stress granule formation contribute to C9orf72 RAN translation-induced cytotoxicity.

    abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Tao Z,Wang H,Xia Q,Li K,Li K,Jiang X,Xu G,Wang G,Ying Z

    更新日期:2015-05-01 00:00:00

  • Mitochondrial respiration without ubiquinone biosynthesis.

    abstract::Ubiquinone (UQ), a.k.a. coenzyme Q, is a redox-active lipid that participates in several cellular processes, in particular mitochondrial electron transport. Primary UQ deficiency is a rare but severely debilitating condition. Mclk1 (a.k.a. Coq7) encodes a conserved mitochondrial enzyme that is necessary for UQ biosynt...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wang Y,Hekimi S

    更新日期:2013-12-01 00:00:00

  • CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

    abstract::Steroid 11 beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol. Severely affected patients carry mutations in the CYB11B1 gene that destroy enzymatic activity. Such patients have signs of androgen excess and usually have hyperten...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Joehrer K,Geley S,Strasser-Wozak EM,Azziz R,Wollmann HA,Schmitt K,Kofler R,White PC

    更新日期:1997-10-01 00:00:00

  • MeCP2 regulates activity-dependent transcriptional responses in olfactory sensory neurons.

    abstract::During postnatal development, neuronal activity controls the remodeling of initially imprecise neuronal connections through the regulation of gene expression. MeCP2 binds to methylated DNA and modulates gene expression during neuronal development and MECP2 mutation causes the autistic disorder Rett syndrome. To invest...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lee W,Yun JM,Woods R,Dunaway K,Yasui DH,Lasalle JM,Gong Q

    更新日期:2014-12-01 00:00:00

  • Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.

    abstract::Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Garcia-Diaz B,Barca E,Balreira A,Lopez LC,Tadesse S,Krishna S,Naini A,Mariotti C,Castellotti B,Quinzii CM

    更新日期:2015-08-15 00:00:00

  • Thrombospondin-1 and disease progression in dysferlinopathy.

    abstract::The purpose of this study was to determine whether thrombospondin (TSP)-1 promotes macrophage activity and disease progression in dysferlinopathy. First, we found that levels of TSP-1 are elevated in blood of non-ambulant dysferlinopathy patients compared with ambulant patients and healthy controls, supporting the ide...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Urao N,Mirza RE,Corbiere TF,Hollander Z,Borchers CH,Koh TJ

    更新日期:2017-12-15 00:00:00

  • Epigenetic defects of hepatocellular carcinoma are already found in non-neoplastic liver cells from patients with hereditary haemochromatosis.

    abstract::Gene silencing through aberrant CpG island methylation is a frequent epigenetic defect in hepatocellular carcinoma (HCC). However, nothing is known as yet whether aberrant hypermethylation occurs already in non-neoplastic liver cells from patients with hereditary haemochromatosis who have a clearly elevated risk for d...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lehmann U,Wingen LU,Brakensiek K,Wedemeyer H,Becker T,Heim A,Metzig K,Hasemeier B,Kreipe H,Flemming P

    更新日期:2007-06-01 00:00:00

  • Identification of disease genes by whole genome CGH arrays.

    abstract::Small, submicroscopic, genomic deletions and duplications (1 kb to 10 Mb) constitute up to 15% of all mutations underlying human monogenic diseases. Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicrosco...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审


    authors: Vissers LE,Veltman JA,van Kessel AG,Brunner HG

    更新日期:2005-10-15 00:00:00

  • Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

    abstract::Mutations in glucokinase (GCK) cause a spectrum of glycemic disorders. Heterozygous loss-of-function mutations cause mild fasting hyperglycemia irrespective of mutation severity due to compensation from the unaffected allele. Conversely, homozygous loss-of-function mutations cause permanent neonatal diabetes requiring...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Raimondo A,Chakera AJ,Thomsen SK,Colclough K,Barrett A,De Franco E,Chatelas A,Demirbilek H,Akcay T,Alawneh H,International NDM Consortium.,Flanagan SE,Van De Bunt M,Hattersley AT,Gloyn AL,Ellard S,International NDM Consor

    更新日期:2014-12-15 00:00:00

  • Mouse Fkbp8 activity is required to inhibit cell death and establish dorso-ventral patterning in the posterior neural tube.

    abstract::Neural tube defects (NTDs) are birth defects that can be disabling or lethal and are second in their prevalence after cardiac defects among major human congenital malformations. Spina bifida is a NTD where the spinal cord is dysplastic, and the overlying spinal column is absent. At present, the molecular mechanisms un...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wong RL,Wlodarczyk BJ,Min KS,Scott ML,Kartiko S,Yu W,Merriweather MY,Vogel P,Zambrowicz BP,Finnell RH

    更新日期:2008-02-15 00:00:00

  • Genetic regulation of gene expression in the epileptic human hippocampus.

    abstract::Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocamp...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,meta分析


    authors: Mirza N,Appleton R,Burn S,du Plessis D,Duncan R,Farah JO,Feenstra B,Hviid A,Josan V,Mohanraj R,Shukralla A,Sills GJ,Marson AG,Pirmohamed M

    更新日期:2017-05-01 00:00:00

  • Loss of cone cyclic nucleotide-gated channel leads to alterations in light response modulating system and cellular stress response pathways: a gene expression profiling study.

    abstract::The cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Mutations in the channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophy. We investigated the gene expression profiles in mouse retina with CNG channel deficiency usin...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ma H,Thapa A,Morris LM,Michalakis S,Biel M,Frank MB,Bebak M,Ding XQ

    更新日期:2013-10-01 00:00:00

  • Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region.

    abstract::An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, ot...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Chartier-Harlin MC,Parfitt M,Legrain S,Pérez-Tur J,Brousseau T,Evans A,Berr C,Vidal O,Roques P,Gourlet V

    更新日期:1994-04-01 00:00:00

  • The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction.

    abstract::P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Herrmann SM,Ricard S,Nicaud V,Mallet C,Evans A,Ruidavets JB,Arveiler D,Luc G,Cambien F

    更新日期:1998-08-01 00:00:00

  • Cloning of the Huntington disease region in yeast artificial chromosomes.

    abstract::The gene responsible for Huntington disease has been localized to a 2.5 million base pair (Mb) region between the loci D4S10 and D4S168 on the short arm of chromosome 4. As part of a strategy to clone the HD gene on the basis of its chromosomal location, we isolated genomic DNA from the HD region as a set of overlappi...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Zuo J,Robbins C,Taillon-Miller P,Cox DR,Myers RM

    更新日期:1992-06-01 00:00:00

  • A sea urchin gene encoding dystrophin-related proteins.

    abstract::The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest known gene. The product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene encodes at least six additional products: two non-muscle dystrophin isoforms transcribed from promoters located in the 5'-end region of the gene...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wang J,Pansky A,Venuti JM,Yaffe D,Nudel U

    更新日期:1998-04-01 00:00:00

  • Reduced protein turnover mediates functional deficits in transgenic mice expressing the 25 kDa C-terminal fragment of TDP-43.

    abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) are two neurodegenerative disorders characterized by the accumulation of TDP-43. TDP-43 is proteolitically cleaved to generate two major C-terminal fragments of 35 and 25 kDa. The latter, known as TDP-25, is a consistent feature of FT...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Caccamo A,Shaw DM,Guarino F,Messina A,Walker AW,Oddo S

    更新日期:2015-08-15 00:00:00

  • The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.

    abstract::The biogenesis of the mitochondrial inner membrane is dependent on two distinct 70 kDa protein complexes. TIMM8a partners with TIMM13 in the mitochondrial intermembrane space to form a 70 kDa complex and facilitates the import of the inner membrane substrate TIMM23. We have identified a new class of substrates, citrin...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Roesch K,Hynds PJ,Varga R,Tranebjaerg L,Koehler CM

    更新日期:2004-09-15 00:00:00

  • Rab11 rescues synaptic dysfunction and behavioural deficits in a Drosophila model of Huntington's disease.

    abstract::Synapse abnormalities in Huntington's disease (HD) patients can precede clinical diagnosis and neuron loss by decades. The polyglutamine expansion in the huntingtin (htt) protein that underlies this disorder leads to perturbations in many cellular pathways, including the disruption of Rab11-dependent endosomal recycli...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Steinert JR,Campesan S,Richards P,Kyriacou CP,Forsythe ID,Giorgini F

    更新日期:2012-07-01 00:00:00

  • The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes.

    abstract::Recent genome-wide association studies (GWAS) have identified a number of novel genetic associations with complex human diseases. In spite of these successes, results from GWAS generally explain only a small proportion of disease heritability, an observation termed the 'missing heritability problem'. Several sources f...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Cusanovich DA,Billstrand C,Zhou X,Chavarria C,De Leon S,Michelini K,Pai AA,Ober C,Gilad Y

    更新日期:2012-05-01 00:00:00

  • Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis.

    abstract::Lysosomal neuraminidase is the key enzyme for the intralysosomal catabolism of sialylated glycoconjugates and is deficient in two neurodegenerative lysosomal disorders, sialidosis and galactosialidosis. Here we report the identification of eight novel mutations in the neuraminidase gene of 11 sialidosis patients with ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Bonten EJ,Arts WF,Beck M,Covanis A,Donati MA,Parini R,Zammarchi E,d'Azzo A

    更新日期:2000-11-01 00:00:00

  • Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.

    abstract::Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in Lesch-Nyhan disease (LND), where affected individuals exhibit a characteristic neurobehavioral disorder that has been linked with dysfunction of dopaminergic pathways of the basal ganglia. Since the functions of HPRT, a housekeeping enzyme res...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ceballos-Picot I,Mockel L,Potier MC,Dauphinot L,Shirley TL,Torero-Ibad R,Fuchs J,Jinnah HA

    更新日期:2009-07-01 00:00:00