Association of congenital cardiovascular malformations with 33 single nucleotide polymorphisms of selected cardiovascular disease-related genes.
Association of congenital cardiovascular malformations with 33 single nucleotide polymorphisms of selected cardiovascular disease-related genes.
复制标题
DOI：
10.1002/bdra.20630
复制
发表时间：
2010-02
影响因子：
--
通讯作者：
Shaw, Gary M.
中科院分区：
文献类型：
--
作者：
Kuehl, Karen;Loffredo, Christopher;Lammer, Edward J.;Iovannisci, David M.;Shaw, Gary M.
提出血流异常与某些先天性心血管畸形（CCVM）有关，特别是伴有血流阻塞的CCVM。我们的假设是，CCVM可能与影响血液凝固或流动的基因有关。我们研究了这些基因的多态性是否与CCVM相关;以前这些SNPs与圆锥动脉干CCVM的相关性被描述。（PS，N=120），房间隔缺损（ASD，N=108）、主动脉瓣狭窄（AS，N=36）和主动脉缩窄（CoAo，N=64），与33个候选基因相关，根据它们与受同型半胱氨酸代谢、凝血、细胞-细胞相互作用、炎症或血压调节影响的血流的关系来选择。效应对心脏表型和人种具有特异性。CoAo与MTHFR（-667）C>T相关（TT的比值比[OR]为3.5，95%置信限[CI]为1.4-8.6）。AS与SERPINE 1基因多态性有关，G5>G4，纯合子OR = 5.6，95%CI为1.4 ~ 22.9。独特的多态性与ASD和PS的风险增加相关：NPPA 664 G>A与ASD（OR为2.4，95%CI 1.3 - 4.4）和NOS 3（−690）C>T与PS（OR 6.1; 95%CI 1.6 - 22.6，仅在非洲裔美国人人群中）。对于ASD，NPPA（−664）G>A SNP仅在母亲吸烟者中存在来自变异基因型的风险增加（OR 2.6; 95%CI 1.0-7.2）。影响血管功能和凝血的基因似乎是心脏畸形病因学的有希望的候选者，值得进一步研究。
proposed that abnormal blood flow is related to some to congenital cardiovascular malformations (CCVM), particularly CCVM with obstruction to blood flow. Our hypothesis is that CCVM may relate to genes that affect blood coagulation or flow. We studied whether polymorphisms of such genes are related to CCVM; previously association of these SNPs conotruncal CCVM is described We assessed risk of pulmonary stenosis (PS, N=120), atrial septal defect (ASD, N=108), aortic stenosis (AS, N=36), and coarctation of the aorta (CoAo, N=64), associated with 33 candidate genes, selected for their relationship to blood flow affected by homocysteine metabolism, coagulation, cell–cell interaction, inflammation, or blood pressure regulation. Effects were specific to cardiac phenotype and race. CoAo was associated with MTHFR (−667) C>T (odds ratio [OR] for TT 3.5, 95% confidence limits [CI] 1.4–8.6). AS was associated with a polymorphism of SERPINE1, G5>G4, OR = 5.6 for the homozygote with 95% CI 1.4 –22.9. Unique polymorphisms were associated with increased risk of ASD and PS: NPPA 664G>A with ASD (OR of 2.4, 95%CI 1.3 – 4.4) and NOS3 (−690) C>T with PS (OR 6.1; 95%CI 1.6 – 22.6 in the African American population only). For ASD, the NPPA (−664) G>A SNP there was increased risk from the variant genotype only in maternal smokers (OR 2.6; 95%CI 1.0–7.2). Genes affecting vascular function and coagulation appear to be promising candidates for the etiology of cardiac malformations and warrant further study.
登录
查看更多内容
影响因子：
158.5
作者：
Girelli, D;Russo, C;Corrocher, R
通讯作者：
Corrocher, R
影响因子：
2.7
作者：
KNUDSEN, KA;MCELWEE, SA;MYERS, L
通讯作者：
MYERS, L
影响因子：
9.3
作者：
Bathum, Lise;Petersen, Inge;Kyvik, Kirsten O.
通讯作者：
Kyvik, Kirsten O.
影响因子：
4
作者：
Hobbs, CA;James, SJ;Cleves, MA
通讯作者：
Cleves, MA
影响因子：
64.8
作者：
Fulton, D;Gratton, JP;Sessa, WC
通讯作者：
Sessa, WC