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.
    Preview · Article · Apr 2013 · International journal of medical sciences
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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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