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本文引用的文献

1
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.大规模关联分析确定了 13 个冠心病新的易感性位点。
Nat Genet. 2011 Mar 6;43(4):333-8. doi: 10.1038/ng.784.
2
Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.常见变异 9p21 的基因剂量可预测冠状动脉疾病的严重程度。
J Am Coll Cardiol. 2010 Aug 3;56(6):479-86. doi: 10.1016/j.jacc.2009.10.092.
3
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.通过大规模的关联分析确定了 12 个 2 型糖尿病易感位点。
Nat Genet. 2010 Jul;42(7):579-89. doi: 10.1038/ng.609.
4
No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents.放置药物洗脱支架后，9p21.3 染色体变异与临床和血管造影结果无关。
JACC Cardiovasc Interv. 2009 Nov;2(11):1149-55. doi: 10.1016/j.jcin.2009.08.021.
5
Genome-wide association study identifies five susceptibility loci for glioma.全基因组关联研究确定了五个胶质瘤易感位点。
Nat Genet. 2009 Aug;41(8):899-904. doi: 10.1038/ng.407. Epub 2009 Jul 5.
6
Genome-wide association study identifies three loci associated with melanoma risk.全基因组关联研究确定了三个与黑色素瘤风险相关的基因座。
Nat Genet. 2009 Aug;41(8):920-5. doi: 10.1038/ng.411. Epub 2009 Jul 5.
7
Genetic variants on chromosome 9p21 and ischemic stroke in Chinese.9号染色体短臂21区的基因变异与中国人群的缺血性脑卒中
Brain Res Bull. 2009 Aug 14;79(6):431-5. doi: 10.1016/j.brainresbull.2009.04.001. Epub 2009 Apr 14.
8
Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease.9p21.3 单倍型多样性的全球分布模式，该区域与 2 型糖尿病和冠心病相关。
Genome Med. 2009 May 12;1(5):51. doi: 10.1186/gm51.
9
Kinesin family member 6 variant Trp719Arg does not associate with angiographically defined coronary artery disease in the Ottawa Heart Genomics Study.在渥太华心脏基因组学研究中，驱动蛋白家族成员6变体Trp719Arg与血管造影定义的冠状动脉疾病无关。
J Am Coll Cardiol. 2009 Apr 21;53(16):1471-2. doi: 10.1016/j.jacc.2008.12.051.
10
Creating a genetic risk score for coronary artery disease.创建冠心病的遗传风险评分。
Curr Atheroscler Rep. 2009 May;11(3):175-81. doi: 10.1007/s11883-009-0028-4.

评估 9p21.3 基因座在 2 型糖尿病存在或不存在时对冠状动脉疾病严重程度的影响。

Assessment of the 9p21.3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes.

机构信息

IRCCS Multimedica, Via Fantoli 16/15, 20138, Milan, Italy.

出版信息

BMC Med Genet. 2013 Jan 23;14:11. doi: 10.1186/1471-2350-14-11.

DOI:10.1186/1471-2350-14-11
PMID:23343465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3556499/
Abstract

BACKGROUND

The 9p21.3 locus is strongly associated with the risk of coronary artery disease (CAD) and with type 2 diabetes (T2D). We investigated the association of 9p21.3 variants with severity of CAD (defined by the number of vessel diseased [VD]) in the presence and absence of T2D.

METHODS

We tested 11 9p21.3-variants for association in a white Italian study (N = 2,908), and carried out replication in 2 independent white populations, a German study (N = 2,028) and a Canadian Study (N=950). SNP association and permutation analyses were conducted.

RESULTS

We identified two 9p21.3-variants, rs4977574 (P < 4×10(-4)) and rs2383207 (P < 1.5×10(-3)) that were associated with severity of CAD in subjects without T2D. Association of rs4977574 with severity of CAD was confirmed in the Canadian Study. Results from subgroup analysis among patients with T2D showed an interaction between rs10738610 and T2D with P = 4.82×10(-2). Further investigation showed that rs10738610 (P < 1.99×10(-2)) was found to be significantly associated with severity of CAD in subjects with T2D.

CONCLUSIONS

The 9p21.3 locus is significantly associated with severity of CAD. The number of associations of 9p21.3 variants with severity of CAD is variable to the presence and absence of T2D. In a CAD-susceptible region of 115 kb, there is only one variant associated with the severity of coronary vessel disease in the presence of type 2 diabetes.

摘要

背景

9p21.3 基因座与冠心病（CAD）和 2 型糖尿病（T2D）的风险密切相关。我们研究了 9p21.3 变体与 CAD 严重程度（通过病变血管数[VD]定义）之间的关联，同时考虑了 T2D 的存在与否。

方法

我们在一个意大利白人研究（N=2908）中测试了 11 个 9p21.3 变体与 CAD 严重程度的关联，并在两个独立的白人人群中进行了复制，一个是德国研究（N=2028），另一个是加拿大研究（N=950）。进行了 SNP 关联和置换分析。

结果

我们发现了两个 9p21.3 变体，rs4977574（P<4×10(-4))和 rs2383207（P<1.5×10(-3))，它们与无 T2D 的 CAD 严重程度相关。rs4977574 与 CAD 严重程度的关联在加拿大研究中得到了证实。在 T2D 患者的亚组分析结果中，rs10738610 与 T2D 之间存在交互作用，P=4.82×10(-2)。进一步的研究表明，rs10738610（P<1.99×10(-2))在患有 T2D 的人群中与 CAD 严重程度显著相关。

结论

9p21.3 基因座与 CAD 的严重程度显著相关。9p21.3 变体与 CAD 严重程度的关联数量因 T2D 的存在与否而不同。在 115kb 的 CAD 易感区域中，只有一个变体在存在 2 型糖尿病的情况下与冠状动脉疾病的严重程度相关。