Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Authority.
PLoS One. 2010 Nov 30;5(11):e15124. doi: 10.1371/journal.pone.0015124.
Chromosome 9p21 has recently been shown to be a risk region for a broad range of vascular diseases. Since carotid intima-media thickness (IMT) and plaque are independent predictors for vascular diseases, the association between 9p21 and these two phenotypes was investigated.
METHODOLOGY/PRINCIPAL FINDINGS: Carotid segment-specific IMT and plaques were obtained in 1083 stroke- and myocardial infarction-free volunteers. We tested the genotypes and haplotypes of key single nucleotide polymorphisms (SNPs) on chromosome 9p21 for the associations with carotid IMT and plaque. Multivariate permutation analyses demonstrated that carriers of the T allele of SNP rs1333040 were significantly associated with thicker common carotid artery (CCA) IMT (p=0.021) and internal carotid artery (ICA) IMT (p=0.033). The risk G allele of SNP rs2383207 was associated with ICA IMT (p=0.007). Carriers of the C allele of SNP rs1333049 were found to be significantly associated with thicker ICA IMT (p=0.010) and the greater risk for the presence of carotid plaque (OR=1.57 for heterozygous carriers; OR=1.75 for homozygous carriers). Haplotype analysis showed a global p value of 0.031 for ICA IMT and 0.115 for the presence of carotid plaque. Comparing with the other haplotypes, the risk TGC haplotype yielded an adjusted p value of 0.011 and 0.017 for thicker ICA IMT and the presence of carotid plaque respectively. Further analyzing the data separated by sex, the results were significant only in men but not in women.
Chromosome 9p21 had a significant association with carotid atherosclerosis, especially ICA IMT. Furthermore, such genetic effect was in a gender-specific manner in the Han Chinese population.
最近研究表明，9 号染色体 p21 是多种血管疾病的风险区域。由于颈动脉内膜中层厚度（IMT）和斑块是血管疾病的独立预测因子，因此研究了 9p21 与这两种表型的关联。
方法/主要发现：在 1083 名无中风和心肌梗死的志愿者中获得颈动脉节段特异性 IMT 和斑块。我们测试了 9p21 上关键单核苷酸多态性（SNP）的基因型和单倍型与颈动脉 IMT 和斑块的关联。多元置换分析表明，SNP rs1333040 的 T 等位基因携带者与颈总动脉（CCA）IMT 增厚显著相关（p=0.021）和颈内动脉（ICA）IMT 增厚显著相关（p=0.033）。SNP rs2383207 的风险 G 等位基因与 ICA IMT 相关（p=0.007）。SNP rs1333049 的 C 等位基因携带者与 ICA IMT 增厚显著相关（p=0.010）和颈动脉斑块的存在风险增加显著相关（杂合子携带者为 1.57；纯合子携带者为 1.75）。单体型分析显示，ICA IMT 的总体 p 值为 0.031，颈动脉斑块的存在的 p 值为 0.115。与其他单体型相比，风险 TGC 单体型的调整后 p 值分别为 0.011 和 0.017，用于更厚的 ICA IMT 和颈动脉斑块的存在。进一步按性别分析数据，结果仅在男性中显著，而在女性中不显著。
9 号染色体 p21 与颈动脉粥样硬化有显著关联，特别是 ICA IMT。此外，这种遗传效应在汉族人群中具有性别特异性。
