Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking.
Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking.
复制标题
DOI：
10.1111/j.1469-1809.2009.00540.x
复制
发表时间：
2009-11
影响因子：
1.9
通讯作者：
Kraus WE
中科院分区：
文献类型：
--
作者：
Horne BD;Hauser ER;Wang L;Muhlestein JB;Anderson JL;Carlquist JF;Shah SH;Kraus WE
CATHGEN研究报告了染色体3q 13 -21基因（KALRN、MYLK、CDGAP和GATA 2）与早发性冠状动脉疾病（CAD）的相关性。本研究试图独立验证这些关联。检测了11个单核苷酸多态性（SNPs）（rs10934490、rs16834817、rs6810298、rs9289231、rs12637456、rs1444768、rs1444754、rs4234218、rs2335052、rs3803、rs2713604）618）来自山间心脏协作研究（IHCS）。鉴于CATHGEN组的吸烟率高于IHCS组（对照组为41% vs 11%，病例组为74% vs 29%），因此对吸烟分层和基因型-吸烟相互作用进行了评价。发现GATA 2存在暗示性关联（rs 2713604，p=0.057，OR=1.2）。在吸烟者中，发现CDGAP（rs 10934490，p=0.019，OR=1.6）和KALRN（rs 12637456，p=0.011，OR=2.0）与MYLK（rs 16834871，p=0.051，OR=1.8，调整性别）相关。在非吸烟者中未发现SNP相关性，但在CDGAP（rs 10934491，p=0.017）和KALRN（rs 12637456，p=0.010）中检测到吸烟/SNP相互作用。在CATHGEN的再分析中观察到吸烟状态对SNP影响的类似差异。CAD关联提示GATA 2，在吸烟者中，在KALRN、MYLK和CDGAP中发现了显著的事后关联。其中一些基因所带来的遗传风险可能会因吸烟而改变。未来对这些和其他基因的CAD关联研究应该评估吸烟的影响。
The CATHGEN study reported associations of chromosome 3q13-21 genes (KALRN, MYLK, CDGAP, and GATA2) with early-onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N=1,618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs 11% in controls, 74% vs 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p=0.057, OR=1.2). Among smokers, associations were found in CDGAP (rs10934490, p=0.019, OR=1.6) and KALRN (rs12637456, p=0.011, OR=2.0) and suggestive association in MYLK (rs16834871, p=0.051, OR=1.8, adjusting for gender). No SNP association was found among non-smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p=0.017) and KALRN (rs12637456, p=0.010). Similar differences in SNP effects by smoking status were observed on re-analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.
登录
查看更多内容
影响因子：
8.7
作者：
Sen-Banerjee, S;Siles, X;Campos, H
通讯作者：
Campos, H
影响因子：
5.3
作者：
Talmud, PJ;Bujac, S;Humphries, SE
通讯作者：
Humphries, SE
影响因子：
24
作者：
Horne, Benjamin D.;Camp, Nicola J.;Carlquist, John F.
通讯作者：
Carlquist, John F.
影响因子：
9.8
作者：
Hauser, ER;Crossman, DC;Kraus, WE
通讯作者：
Kraus, WE
影响因子：
39.3
作者：
Freeman, DJ;Samani, NJ;Gaffney, D
通讯作者：
Gaffney, D