Björck H M, Länne T, Alehagen U, Persson K, Rundkvist L, Hamsten A, Dahlström U, Eriksson P
Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
J Intern Med. 2009 Mar;265(3):373-81. doi: 10.1111/j.1365-2796.2008.02020.x. Epub 2008 Oct 25.
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.
全基因组关联研究一致报道9号染色体p21.3区域与多种血管疾病相关，如冠状动脉疾病（CAD）、主动脉瘤和颅内动脉瘤以及2型糖尿病（T2D）。然而，迄今为止尚未描述与中间表型的明确关联。为了阐明该染色体区域对动脉壁完整性的可能影响，我们分析了老年个体中单核苷酸多态性（SNP）与腹主动脉僵硬度之间的关联。
共纳入400名受试者，年龄在70 - 88岁之间，其中男性212名，女性188名。在肾动脉与主动脉分叉之间的中点处检测动脉僵硬度。对9p21.3区域内两个与CAD和动脉瘤相关的SNP（rs10757274和rs2891168）以及一个与T2D相关的SNP（rs1081161）进行基因分型。男性中携带rs10757274G和rs2891168G等位基因者的主动脉顺应性和扩张系数较高，反映出主动脉僵硬度降低。对年龄和平均动脉压进行校正后，这些关联无变化。这两个SNP与腹主动脉内膜中层厚度或管腔直径无关。rs10811661 SNP与任何主动脉僵硬度指标均无关联。
动脉壁力学性能受损可能解释9号染色体p21.3多态性与血管疾病之间的关联。
