ABSTRACT
OBJECTIVE: To compare the preference of food saltiness and the willingness to consume low-sodium food among hypertensive older people, non-hypertensive older people and non-hypertensive young people in a Chinese population. DESIGN: A cross-sectional study based on a quota sample. Three saltiness options (low-sodium, medium-sodium and high-sodium) of soup and bread were offered to each participant who rated the taste of each food on a 5-point Likert scale. Then, the participants rated their willingness to consume the low-sodium content foods on a 5-point Likert scale, given they were informed of the benefit of the low-sodium option. Generalised linear mixed model and multiple linear regression were used to analyse the data. SETTING: Elderly centres and community centres in Hong Kong. PARTICIPANTS: Sixty hypertensive older people, 49 non-hypertensive older people and 60 non-hypertensive young people were recruited from June to August 2014. MEASUREMENTS: The tastiness score and the willingness score were the primary outcome measures. The Chinese Health Literacy Scale for Low Salt Consumption - Hong Kong population (CHLSalt-HK) was also assessed. RESULTS: The tastiness rating of the high-sodium option of soup was significantly lower than the medium-sodium option (p<0.001), but there was no significant difference between the low-sodium and the medium-sodium options (p=0.204). For bread, tastiness rating of the low-sodium option and the high-sodium option were significantly lower than the medium-sodium option (p<0.001 for both options). The tastiness score of soup did not have significant difference across the groups (p=0.181), but that of bread from the hypertensive older adults (p=0.012) and the non-hypertensive older adults (p=0.006) was significantly higher than the non-hypertensive young adults. Higher willingness rating to consume the low-sodium option was significantly (p<0.001) associated with higher tastiness rating of the low-sodium option of soup and bread, and weakly associated with higher health literacy of low salt intake (soup: p=0.041; bread: p=0.024). Hypertensive older adults tended to be more willing to consume the low-sodium option than non-hypertensive older adults for soup (p=0.009), there was insignificant difference between non-hypertensive older adults and non-hypertensive young adults (p=0.156). For bread, there was insignificant difference in willingness rating to consume low-sodium option (p=0.375). CONCLUSION: Older people are at a higher risk of hypertension, reduction of salt intake is important for them to reduce their risk of cardiovascular diseases. There is room for reducing the sodium content of soup, while the sodium in bread should be reduced progressively. Improving the taste of low-sodium food may help to promote reduction in dietary sodium intake.
Subject(s)
Asian People/psychology , Diet, Sodium-Restricted/psychology , Food Preferences/psychology , Sodium Chloride, Dietary/administration & dosage , Adolescent , Adult , Aged , Blood Pressure/drug effects , Case-Control Studies , Cross-Sectional Studies , Female , Hong Kong , Humans , Hypertension/diet therapy , Hypertension/drug therapy , Linear Models , Male , Middle Aged , Socioeconomic Factors , Taste , Young AdultABSTRACT
In this report we examine the (AC)n(AT)xTy motif residing -530 bp 5' upstream of the beta-globin gene in Chinese thalassaemic patients. This motif is a putative binding site for a repressor protein, termed beta protein 1 (BP1) (Berg et al., Nucleic Acids Res 1989;17:8833-8852). Variations in the (AC)n(AT)xTy repeats affect the binding affinity of BP1, thereby altering the expression of the beta-globin gene. Eight different configurations of this repeat motif are identified in our population of Chinese beta-thalassaemia patients. A (AC)3(AT)7T5 motif was identified among these thalassaemia patients and its influence in beta-globin gene expression was studied using stable transfection assay in murine erythroleukemia (MEL) cells. Our data demonstrated that the (AC)3(AT)7T5 motif has a moderately strong repressor effect on the expression of the cis-linked beta-globin gene. The high affinity of BP1 for this motif may result in the suppression of the transcription of the beta-globin gene (Berg et al., Am J Hematol 1991;36:42-47). We postulate that silencer elements in the beta-globin promoter play an important role in modifying the clinical presentation of the disease.
Subject(s)
5' Untranslated Regions/genetics , Globins/genetics , Promoter Regions, Genetic/genetics , Silencer Elements, Transcriptional/genetics , beta-Thalassemia/genetics , Animals , Binding Sites , Cell Differentiation , Cell Line, Tumor , Fetal Hemoglobin/analysis , Gene Expression Regulation , Globins/biosynthesis , Homeodomain Proteins/metabolism , Hong Kong , Humans , Leukemia, Erythroblastic, Acute/pathology , Mice , Repressor Proteins/metabolism , Transcription Factors/metabolism , Transcription, Genetic , Transfection , beta-Thalassemia/ethnologyABSTRACT
Previously, we found that secretin transcript levels were induced by all-trans retinoic acid (RA) in a neuroblastoma cell model, SH-SY5Y. In this article, this RA-dependent upregulation process was further investigated. In the cyclin-dependent kinase 1 (Cdk1) inhibitor-treated cells, the RA-dependent induction of secretin gene expression was inhibited. Together with our previous works, we propose here that the RA responsiveness of the secretin promotor is mediated by two different pathways. The first pathway is by changing the expression levels of NFI-C and Sp proteins while the second pathway is by modifying the phosphorylation status of both NFI-C and Sp proteins via Cdk1.
Subject(s)
CDC2 Protein Kinase/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Neuroblastoma/enzymology , Neuroblastoma/genetics , Secretin/genetics , Tretinoin/pharmacology , CDC2 Protein Kinase/antagonists & inhibitors , Cell Line, Tumor , Humans , Protein Kinase Inhibitors/pharmacologyABSTRACT
We have cloned, sequenced and annotated segments of DNA spanning the mouse, chicken and pufferfish alpha globin gene clusters and compared them with the corresponding region in man. This has defined a small segment ( approximately 135-155 kb) of synteny and conserved gene order, which may contain all of the elements required to fully regulate alpha globin gene expression from its natural chromosomal environment. Comparing human and mouse sequences using previously described methods failed to identify the known regulatory elements. However, refining these methods by ranking identity scores of non-coding sequences, we found conserved sequences including the previously characterized alpha globin major regulatory element. In chicken and pufferfish, regions that may correspond to this element were found by analysing the distribution of transcription factor binding sites. Regions identified in this way act as strong enhancer elements in expression assays. In addition to delimiting the alpha globin chromosomal domain, this study has enabled us to develop a more sensitive and accurate routine for identifying regulatory elements in the human genome.
Subject(s)
Chromosomes/chemistry , Chromosomes/genetics , Globins/genetics , Multigene Family/genetics , Regulatory Sequences, Nucleic Acid , Animals , Base Sequence , Chickens , Conserved Sequence/genetics , CpG Islands/genetics , Evolution, Molecular , Fishes , Globins/chemistry , Humans , Mice , Molecular Sequence Data , Nucleic Acid Hybridization/methods , Protein Structure, Tertiary/genetics , Regulatory Sequences, Nucleic Acid/physiologyABSTRACT
Effective gene therapy constructs based on retrovirus or adeno-associated virus vectors will require regulatory elements that direct expression of genes transduced at single copy. Most beta-globin constructs designed for therapy of beta-thalassemias are regulated by the 5'HS2 component of the locus control region (LCR). Here we show that a human beta-globin gene flanked by two small 5'HS2 core elements or flanked by a 5'HS3 (footprints 1-3) core and a 5'HS2 core are not reproducibly expressed in single copy transgenic mice. In addition, low copy transgene concatamers that contain only dimer 5'HS2 cores fail to express, whereas those that contain monomer 5'HS2 cores express at 14% per copy. These data suggest that spacing between HS cores is crucial for LCR activity. We therefore constructed a novel 3.0 kb LCR cassette in which the 5'HS2, 5'HS3 and 5'HS4 cores are each separated by approximately 700 bp. When linked to the 815 bp beta-globin promoter this LCR directs 45% levels of expression from four independent single copy transgenes. However, the 3.0 kb LCR linked to the 265 bp promoter expresses variable levels, averaging 18%, from three single copy transgenes. Our findings suggest that sequences in the distal promoter play a role in single copy transgene activation and that larger LCR and promoter elements are most suitable for gene therapy applications.
Subject(s)
Genetic Therapy , Globins/genetics , Mice, Transgenic , Animals , DNA Primers , DNA Transposable Elements , Dimerization , Fetus , Gene Expression , Globins/biosynthesis , Humans , Liver/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred Strains , Polymerase Chain Reaction , Promoter Regions, Genetic , Reproducibility of ResultsABSTRACT
Single-copy human beta-globin transgenes are very susceptible to suppression by position effects of surrounding closed chromatin. However, these position effects are overcome by a 20 kbp DNA fragment containing the locus control region (LCR). Here we show that the 6.5 kbp microlocus LCR cassette reproducibly directs full expression from independent single-copy beta-globin transgenes. By testing individual DNase I-hypersensitive sites (HS) present in the microlocus cassette, we demonstrate that the 1.5 kbp 5'HS2 enhancer fragment does not direct beta-globin expression from single-copy transgenes. In contrast, the 1.9 kbp 5'HS3 fragment directs beta-globin expression in five independent single-copy transgenic mouse lines. Moreover, the 5'HS3 core element and beta-globin proximal promoter sequences are DNase I hypersensitive in fetal liver nuclei of these expressing transgenic lines. Taken together, these results demonstrate that LCR activity is the culmination of at least two separable functions including: (i) a novel activity located in 5'HS3 that dominantly opens and remodels chromatin structure; and (ii) a recessive enhancer activity residing in 5'HS2. We postulate that the different elements of the LCR form a 'holocomplex' that interacts with the individual globin genes.