A Haplotype of the Catalase Gene Confers an Increased Risk of Essential Hypertension in Chinese Han
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China. Human Mutation
(Impact Factor: 5.14).
03/2010; 31(3):272-8. DOI: 10.1002/humu.21185
Our previous study in an isolated population showed an association between a genetic variant in the catalase gene (CAT) and essential hypertension (EH). This study indicates that three variants in the promoter and 5'-UTR region of CAT are predominant in Chinese Han, and they form two major haplotypes. A case-control study showed that the CATH2 haplotype confers susceptibility to EH (Pgenotype=0.0017, and Pallilc=0.00078). Subjects bearing CATH1/CATH2 and CATH2/CATH2 genotypes demonstrated a higher susceptibility to EH than CATH1/CATH1 homozygotes, with odds ratios of 1.474 and 1.625, respectively. Also, CATH1/CATH1 individuals had a later-onset age (P=0.015). Expression analysis using luciferase reporter vectors indicated that the CATH1 haplotype showed a lower transcriptional activity than the haplotype CATH2 (P<0.05 in all four cell lines), and we observed similar results in the endogenous allelic expression ratios of CATH1/CATH2 in cell lines. In contrast, most CATH1 haplotypes showed a higher transcription level than CATH2 haplotypes (10 out of 11 or 90.9%) in blood from normal individuals (P<0.01). We therefore hypothesize that CATH1 and CATH2 may play alternating roles at different level of oxidative stress.
Available from: Said El Shamieh
- "Recently, Wang et al. demonstrated that subjects bearing the [-844A, -89T, -20C] haplotype presented a higher susceptibility to essential HTN and a precocious onset for HTN when compared with those carrying the [-844G, -89A, -20T] haplotype of the CAT gene . Our hypothesis was therefore that the CAT haplotype may be implicated in the pace of age-related arterial alterations. "
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Although many conventional factors have been associated with the development of arterial aging, cardiovascular diseases remain the first cause of death in old age. Therefore, identification of new risk factors may prove promising for monitoring this serious health problem. Oxidative stress and particularly catalase (CAT), an antioxidant enzyme, play an important role in endothelial cell pathophysiology, in shear stress response and ultimately in arterial aging.
Examine the relationships between CAT haplotypes and phenotypes of arterial aging (mean internal diameter, mean intima-media thickness of the common carotid arteries (CCA), presence of atheromatous plaques) in two French cohorts.
Methods and results:
564 middle-aged French individuals (mean age 53 ± 12 years) from two cohorts (ERA and STANISLAS cohorts) were included in the study. Blood pressure, CCA intima-media thickness, CCA internal diameter and number of atheromatous plaques were measured. Catalase rs769214 SNP genotyping was performed. We identified a CAT haplotype that influences arterial aging. Individuals carrying the CAT2 haplotype had a higher mean internal diameter of CCA with aging and/or with an SBP ≥140 mmHg and were associated with a greater number of atheromatous plaques than CAT1 haplotypes carriers. This CAT2 haplotype appeared as an independent risk factor of arterial aging, similarly to previously identified factors such as age, systolic blood pressure, male, sex, tobacco use, hs-CRP, BMI and diabetes.
The present study highlights the roles of CAT haplotypes in arterial aging and underlines the beneficial impact of the CAT1 haplotype on mean internal diameter of the CCA and atheromatous plaque number as well as on potential associated diseases.
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ABSTRACT: A concept called the Information-Sciences Experiment System (ISES) is proposed which makes use of the earth observing system (EOS) to evaluate the role of onboard information extraction in space flight systems. Onboard information extraction is a possible part of the solution to the growing data glut problem associated with earth-viewing remote sensors. The ISES concept offers additional opportunities in better utilization of onboard instrumentation, real-time response to events, and a way to evaluate technology in space without jeopardizing mission safety. Finally, the applicability of the ISES concept to the core station is discussed, including important differences between a possible EOS version and core station version of the ISES concept
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ABSTRACT: Impaired glucose tolerance is common during aging. The transcription factor PAX6 is involved in glucose homeostasis. Computational promoter sequence analysis of the catalase gene highlighted a putative PAX6 binding site on the rs769214 polymorphism A allele. Creation of this binding site has been suggested to explain renutrition inefficiency in malnourished elderly patients. Our aim was to evaluate the link between the rs769214 polymorphism of the catalase gene and glucose homeostasis in malnourished elderly patients at inclusion and during renutrition. Thirty-three malnourished elderly Caucasian inpatients were recruited. Nutritional and inflammatory statuses were assessed and a multiplex adipokine analysis was conducted at inclusion and discharge from the Geriatric Nutritional Care Unit at Charles-Foix Hospital (Ivry-sur-Seine, France). Serum glucagon, PAI-1, and TNF-α levels were significantly lower in the A-allele carriers at inclusion. During renutrition, A-allele carriers exhibited increased serum glucagon, PAI-1, and TNF-α variation. After renutrition, levels of these parameters were similar for A-allele carriers and G-allele carriers. A logistic ordinal multivariate regression analysis linked only variation of glucagon to rs769214 SNP. These results support a role for catalase SNP in the efficiency of renutrition in malnourished elderly patients via the modulation of glucagon secretion, probably involving PAX6.
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