Association of genetic variation on chromosome 9p21.3 and arterial stiffness
Association of genetic variation on chromosome 9p21.3 and arterial stiffness
复制标题
DOI：
10.1111/j.1365-2796.2008.02020.x
复制
发表时间：
2009-03-01
影响因子：
11.1
通讯作者：
Eriksson, P.
中科院分区：
文献类型：
--
作者：
Bjorck, H. M.;Lanne, T.;Eriksson, P.
Bjorck HM，LAnne T，Alejandro U，Rundkvist K，Rundkvist L，Hamsten A，Dahlstrom U，Eriksson P（Linkoping University，Linkoping; and Karolinska Institute，斯德哥尔斯德哥尔摩; Sweden）.染色体9p21.3的遗传变异与动脉硬化的关系。J Intern Med 2009; 265：373- 381.全基因组关联研究已经一致地报道了染色体9p21.3上的区域与广泛的血管疾病（例如冠状动脉疾病（CAD）、主动脉和颅内动脉瘤以及2型糖尿病（T2 D））之间的关联。然而，迄今为止尚未描述与中间表型的明确关联。为了阐明这一染色体区域对动脉壁完整性的可能影响，我们分析了单核苷酸多态性（SNP）与老年人腹主动脉僵硬度之间的关系。共有400名受试者，其中男性212名，女性188名，年龄70-88岁。在肾动脉和主动脉分叉之间的中点检查动脉硬度。对9p21.3区域内的两个CAD和糖尿病相关SNP（rs 10757274和rs 2891168）和一个T2 D相关SNP（rs 1081161）进行基因分型。男性rs 10757274 G和rs 2891168 G等位基因携带者的主动脉顺应性和扩张性系数较高，反映了主动脉僵硬度的降低。年龄和平均动脉压的调整对这些关联没有影响。这两个SNP与腹主动脉内膜中层厚度或管腔直径无关。rs 10811661单核苷酸多态性与任何测量主动脉僵硬度之间均无关联，动脉壁机械性能受损可能解释染色体9p21.3多态性与血管疾病之间的关联。
Bjorck HM, LAnne T, Alehagen U, Persson K, Rundkvist L, Hamsten A, Dahlstrom U, Eriksson P (Linkoping University, Linkoping; and Karolinska Institute, Stockholm; Sweden). Association of genetic variation on chromosome 9p21.3 and arterial stiffness. J Intern Med 2009; 265:373-381.Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals.A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.