Genetic analysis of six SNPs in candidate genes associated with high cross-race risk of development of thoracic aortic aneurysms and dissections in Chinese Han population

Abstract

Aim: Genetic susceptibility is an important risk factor for aortic aneurysm and dissection. Recent case-control association studies have identified six single nucleotide polymorphisms (SNPs) associated with abdominal aortic aneurysm (AAA) in a Caucasian population. We aimed to determine whether these loci confer susceptibility to thoracic aortic dissection (TAD) in a Chinese Han population and thus to establish cross-race susceptibility to TAD. Methods: This study analyzed blood DNA isolated from 206 TAD patients and 180 controls from the ethnic Chinese Han population. Six SNPs -rs819146, rs8003379, rs2853523, rs326118, rs3788205, and rs10757278 -were genotyped using high-throughput matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Results: The A allele frequency for the SNP on 9p21, tagged as rs10757278, was higher in male TAD patients than in male controls (P=0.017). Moreover, with adjustment for traditional cardiovascular risk factors (sex, age, hypertension, dyslipidemia, diabetes, and smoking), the rs10757278 [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.43 to 0.93] polymorphism was found to be an independent susceptibility factor for TAD in men. Conclusion: Our results suggest that a sequence variant on 9p21 is an important susceptibility locus that confers high cross-race risk for development of TAD in Chinese Han population.

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population

“…Recently, four MMP-9 and TIMP-3 singlenucleotide polymorphisms (SNPs) have been identified to be associated with the pathogenesis of PACG [12] and cancer [13,14] in several studies. SNPs are the most common genetic varia-www.nature.com/aps Wang XL et al Acta Pharmacologica Sinica npg tion in the human genome, which could explain differences in genetic susceptibility to complex disease [15] . It remains unclear whether these four SNPs that are associated with some tissue remodeling-related diseases could influence the formation of TAD.…”

Does the 9p21 Genetic Variant Have a Role in Cardiovascular Risk Prediction?

“…Incident hospitalizations due to heart failure were also associated with the same variants in the 9p21 region in the ARIC study Caucasian participants [14]. Studies have also shown associations between 9p21 variation and related outcomes, including aortic aneurysms [15][16][17], intracranial aneurysms [15], and sudden death [18].…”

Segmental mediolytische Arteriopathie – Ursachenforschung bei unter 60-jährigen Patienten mit Aneurysmen und Dissektionen

“…Dazu gehören CD4, CD45, NPTx2, FAM20B, LAMA2, die zur Abgrenzung der SMA dienen können. Die gleiche Arbeitsgruppe um Kuivaniemi hat herausgefunden, dass 17 % der AAA-Gene in Zusammenhang mit der Ca++-Signaltransduktion stehen [15][16][17]. In Zukunft wäre es denkbar, dass ein Zusammenhang besteht zwischen dem arteriellen Hypertonus und der segmentalen Dysregulation der adventitiellen Barorezeptoren (Vasopression und Vasoprotektion) mit konsekutiver Ausbildung von mediolytischen Aneurysmen und Dissektionen.…”

“…In Fallbeschreibungen findet man eine morphologische Gemeinsamkeit, die sich als segmental mediolytische Arteriopathie (SMA) beschreiben lässt. Fragestellung: Lassen sich aus einer Gruppe von 16 Patienten und anhand einzelner Berichte in der Literatur weitere morphologische Parallelen finden, die Hinweise auf die Pathogenese beinhalten? Material und Methoden: In einer prospektiven Prognosestudie wurden vom 01.…”