A study on polymorphisms of elastin gene in Chinese Han patients with isolated systolic hypertension. Am J Hypertens

Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
American Journal of Hypertension (Impact Factor: 2.85). 03/2009; 22(6):656-62. DOI: 10.1038/ajh.2009.53
Source: PubMed


Elastin (ELN) is mainly located in the internal elastic lamina of large arteries. Degradation of ELN is expected to induce large vessel stiffness, which could lead to elderly systolic hypertension. Recent studies have shown that polymorphism of ELN is associated with stiffness of elastic arteries and elevated blood pressure; however, there are no further studies on isolated systolic hypertension (ISH).
We identified the genotype of the ELN gene in 358 patients with ISH, 413 essential hypertension (EH) patients with elevated diastolic blood pressure (DBP), and 244 age-matched normotensive (NT) controls for five single-nucleotide polymorphisms (SNPs) and detected the brachial-ankle pulse wave velocity (baPWV), C-reactive protein (CRP), and intima-media thickness (IMT) for these patients.
ISH was statistically significant in association with SNP rs34208922 (A allele frequency was 0.068 in ISH patients, 0.036 in EH patients, and 0.014 in NT controls; P < 0.001, P(corr) < 0.005) and possibly with SNP rs2071307 (A allele frequency was 0.103 in ISH patients, 0.079 in EH patients, and 0.047 in NT controls; P = 0.002, P(corr) = 0.01), however, the A allele frequency was not different between ISH patients and EH patients. In addition, baPWV and CRP were significantly associated with SNP rs34208922 and rs2071307. The other three SNPs were not significantly associated with ISH, baPWV, CRP, or IMT. Haplotypes of TGGTA and TGAT- were also significantly associated with ISH (P = 0.0001, P(corr) = 0.0021; P = 0.0023, P(corr) = 0.0483).
Variants within the ELN gene are associated with increased risk of ISH and aortic stiffness in the Chinese Han population.

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    • "Artery stiffness and endothelial dysfunction are the main cause of ISH, all the factors which promoted artery stiffness and endothelial dysfunction might be involved in the development of ISH. In this study, We have demonstrated that the baPWV, ET-1 in ISH patients were significantly higher compared with EH patients and NT controls, as described in our last study previously32, studies have reported that artery stiffness was reversely correlated with endothelial function in ISH patients, in the present study, we also found that FMD and NO in ISH patients and EH patients were markedly lower than NT controls, although those in ISH patients were not significantly different with EH patients, and suggested that artery stiffness and endothelial function might be affected each other. "
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    ABSTRACT: Background and aims: Large artery stiffness and endothelial dysfunction are the predominant characteristic of isolated systolic hypertension. Recently studies have revealed MMP1, 3, 9 and TIMP3 Genes polymorphism were associated with arterial stiffness, but the relationship with isolated systolic hypertension were not further studied. This study was to investigate the associations of MMP1,3,9 and TIMP3 Genes polymorphism with isolated systolic hypertension. Methods: We identified the genotype of the genes in 503 patients with isolated systolic hypertension, 481 essential hypertension patients with elevated diastolic blood pressure and 244 age-matched normotensive controls for 5 SNPs and detected the brachial-ankle pulse wave velocity, flow-mediated dilatation, endothelin-1 and nitric oxide among the participants. Results: Multinomial logistic analyses showed that the 5A allele of rs3025058(5A/6A) in MMP3 and the T allele of rs3918242(C-1562T) in MMP9 were significantly associated with isolated systolic hypertension after adjusted by age, triglyceride, low-density lipoprotein (P<0.001, Pcorr<0.003; P=0.009, Pcorr=0.027). The 5A/G/C and 6A/A/T haplotypes were significantly associated with isolated systolic hypertension (Permutation p=0.0258; Permutation p=0.000002). In addition, the brachial-ankle pulse wave velocity of different genotypes for the 5A/6A and C-1562T polymorphisms was significantly highest in 5A or T homozygotes (P<0.01), however, the flow-mediated dilatation and nitric oxide were markedly lowest in 5A or T homozygotes (P<0.01). Conclusion: MMP3 and MMP9 genes variant seem to contribute to the development of isolated systolic hypertension by affecting arterial stiffness and endothelial function.
    International journal of medical sciences 04/2013; 10(7):840-7. DOI:10.7150/ijms.5728 · 2.00 Impact Factor
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    • "This hypothesis is supported by studies linking mutations in elastin with more complex multifactorial manifestations of cardiovascular disease [30], [31]. For example, several genetic association studies have linked elastin with the development of intracranial aneurysms (IA) [30], [32], [33] as well as increased risk of isolated systolic hypertension [34] and age-related alterations in carotid artery distensibility [35]. "
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    ABSTRACT: Elastin is a major structural component of elastic fibres that provide properties of stretch and recoil to tissues such as arteries, lung and skin. Remarkably, after initial deposition of elastin there is normally no subsequent turnover of this protein over the course of a lifetime. Consequently, elastic fibres must be extremely durable, able to withstand, for example in the human thoracic aorta, billions of cycles of stretch and recoil without mechanical failure. Major defects in the elastin gene (ELN) are associated with a number of disorders including Supravalvular aortic stenosis (SVAS), Williams-Beuren syndrome (WBS) and autosomal dominant cutis laxa (ADCL). Given the low turnover of elastin and the requirement for the long term durability of elastic fibres, we examined the possibility for more subtle polymorphisms in the human elastin gene to impact the assembly and long-term durability of the elastic matrix. Surveys of genetic variation resources identified 118 mutations in human ELN, 17 being non-synonymous. Introduction of two of these variants, G422S and K463R, in elastin-like polypeptides as well as full-length tropoelastin, resulted in changes in both their assembly and mechanical properties. Most notably G422S, which occurs in up to 40% of European populations, was found to enhance some elastomeric properties. These studies reveal that even apparently minor polymorphisms in human ELN can impact the assembly and mechanical properties of the elastic matrix, effects that over the course of a lifetime could result in altered susceptibility to cardiovascular disease.
    PLoS ONE 09/2012; 7(9):e46130. DOI:10.1371/journal.pone.0046130 · 3.23 Impact Factor
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    ABSTRACT: Elastin is a key extracellular matrix protein that is critical to the elasticity and resilience of many vertebrate tissues including large arteries, lung, ligament, tendon, skin, and elastic cartilage. Tropoelastin associates with multiple tropoelastin molecules during the major phase of elastogenesis through coacervation, where this process is directed by the precise patterning of mostly alternating hydrophobic and hydrophilic sequences that dictate intermolecular alignment. Massively crosslinked arrays of tropoelastin (typically in association with microfibrils) contribute to tissue structural integrity and biomechanics through persistent flexibility, allowing for repeated stretch and relaxation cycles that critically depend on hydrated environments. Elastin sequences interact with multiple proteins found in or colocalized with microfibrils, and bind to elastogenic cell surface receptors. Knowledge of the major stages in elastin assembly has facilitated the construction of in vitro models of elastogenesis, leading to the identification of precise molecular regions that are critical to elastin-based protein interactions.
    Advances in protein chemistry 02/2005; 70:437-61. DOI:10.1016/S0065-3233(05)70013-9 · 0.75 Impact Factor
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