- 作者：Jane F. Ferguson ; Gregory J. Matthews ; Raymond R. Townsend ; Dominic S. Raj ; Peter A. Kanetsky ; Matthew Budoff ; Michael J. Fischer ; Sylvia E. Rosas ; Radhika Kanthety ; Mahboob Rahman ; Stephen R. Master ; Atif Qasim ; Mingyao Li ; Nehal N. Mehta ; Haiqing Shen ; Braxton D. Mitchell ; Jeffrey R. O'Connell ; Alan R. Shuldiner ; Weang Kee Ho ; Robin Young ; et al.
- 关键词：candidate genes ; chronic kidney disease (CKD) ; Chronic Renal Insufficiency Cohort Study (CRIC) ; coronary artery calcification (CAC) ; myocardial infarction (MI) ; risk factors ; single nucleotide polymorphisms (SNPs)
- 刊名：Journal of the American College of Cardiology
- 出版年：2013
- 出版时间：27 August, 2013
- 年：2013
- 卷：62
- 期：9
- 页码：789-798
- 全文大小：267 K
Objectives
This study sought to identify loci for coronary artery calcification (CAC) in patients with chronic kidney disease (CKD).Background
CKD is associated with increased CAC and subsequent coronary heart disease (CHD), but the mechanisms remain poorly defined. Genetic studies of CAC in CKD may provide a useful strategy for identifying novel pathways in CHD.
Methods
We performed a candidate gene study (¡«2,100 genes; ¡«50,000 single nucleotide polymorphisms [SNPs]) of CAC within the CRIC (Chronic Renal Insufficiency Cohort) study (N?= 1,509; 57 % European, 43 % African ancestry). SNPs with preliminary evidence of association with CAC in CRIC were examined for association with CAC in the PennCAC (Penn Coronary Artery Calcification) (N?= 2,560) and AFCS (Amish Family Calcification Study) (N?= 784) samples. SNPs with suggestive replication were further analyzed for association with myocardial infarction (MI) in the PROMIS (Pakistan Risk of Myocardial Infarction Study) (N?= 14,885).
Results
Of 268 SNPs reaching p?< 5?¡Á 10?4 for CAC in CRIC, 28 SNPs in 23 loci had nominal support (p?< 0.05 and in same direction) for CAC in PennCAC or AFCS. Besides chr9p21 and COL4A1, known loci for CHD, these included SNPs having reported genome-wide association study association with hypertension (e.g., ATP2B1). In PROMIS, 4 of the 23 suggestive CAC loci (chr9p21, COL4A1, ATP2B1, and ABCA4) had significant associations with MI, consistent with their direction of effect on CAC.
Conclusions
We identified several loci associated with CAC in CKD that also relate to MI in a general population sample. CKD?imparts a high risk of CHD and may provide a useful setting for discovery of novel CHD genes and pathways.