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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.

SUBMITTER: Liu O

PROVIDER: S-EPMC4012906 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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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.

Liu Ou O Li Jian-rong JR Gong Ming M Xu Ming M Du Jie J Zhang Hong-jia HJ

Acta pharmacologica Sinica 20100927 10

<h4>Aim</h4>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.<h4>Methods</h4>This study analyzed blood DNA ...[more]

PMID: 20871623

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Project description:BackgroundThoracic aortic aneurysms and dissections (TAAD) is a critical condition that often goes undiagnosed with fatal consequences. While majority of the cases are sporadic, more than 20% are inherited as a single gene disorder. The most common familial TAA is Marfan syndrome (MFS), which is primarily caused by mutations in fibrillin-1 (FBN1) gene. Patients with FBN1 mutations are at higher risk for dissection compared to other patients with similar size aneurysms.MethodsFifteen family members were genotyped using Affymetrix-10K genechips. A genome-wide association study was carried out using an autosomal dominant model of inheritance with incomplete penetrance. Mutation screening of all exons and exon-intron boundaries of FBN1 gene which reside near the peak Lod score was carried out by direct sequencing.ResultsThe index case presented with agonizing substernal pain and was found to have TAAD by transthoracic echocardiogram. The family history was significant for 3 first degree relatives with TAA. Nine additional family members were diagnosed with TAA by echocardiography examinations. The affected individuals had no syndromic features. A genome-wide analysis of linkage mapped the disease gene to a single locus on chromosome 15q21 with a peak Lod score of 3.6 at fibrillin-1 (FBN1) gene locus (odds ratio > 4000:1 in favour of linkage), strongly suggesting that FBN1 is the causative gene. No mutation was identified within the exons and exon-intron boundaries of FBN1 gene that segregated with the disease. Haplotype analysis identified additional mutation carriers who had previously unknown status due to borderline dilation of the ascending aorta.ConclusionsA familial non-syndromic TAAD is strongly associated with the FBN1 gene locus and has a malignant disease course often seen in MFS patients. This finding indicates the importance of obtaining detailed family history and echocardiographic screening of extended relatives of patients with non-syndromic TAAD to improve the outcome. In addition, association of non-syndromic TAAD with the Marfan disease gene locus poses the question whether secondary prevention strategies employed for Marfan syndrome patients should be applied to all patients with familial TAAD.

Dataset Information

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.

Publications

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.

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