Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor.
Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor.
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DOI：
10.1002/bdra.20507
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发表时间：
2008-10
影响因子：
--
通讯作者：
Whitehead, Alexander S.
中科院分区：
文献类型：
--
作者：
Lu, Zhi-Yong;Morales, Megan;Khartulyari, Stephanie;Mei, Minghua;Murphy, Kristen M.;Stanislawska-Sachadyn, Anna;Summers, Carolyn M.;Huang, Yuehua;Von Feldt, Joan M.;Blair, Ian A.;Mitchell, Laura E.;Whitehead, Alexander S.
关键词：
CCL-2基因型（- 2518）A>G启动子多态性为AA型的女性，其后代患脊柱裂的风险可能更高，CCL-2基因型编码强效促炎趋化因子单核细胞趋化蛋白1 （MCP-1）。由于该位点的A等位基因与MCP-1 mRNA转录相对于G等位基因减少有关，因此观察到的遗传关联表明，MCP-1水平低的女性的后代患脊柱裂的风险可能增加。本研究旨在确定育龄妇女MCP-1水平的潜在决定因素。招募了一小群育龄白人和非裔美国妇女，对几种疾病相关生化表型（包括MCP-1）的决定因素进行了探索性调查。受试者完成了一份简短的问卷，并提供了用于生化和基因研究的空腹血液样本。使用线性回归分析评估潜在的生化、遗传和生活方式因素与MCP-1水平的关系。在这个队列中，白人的MCP-1水平明显高于非裔美国人。此外，在两个种族的女性中，有证据表明MCP-1水平与吸烟状况、MTHFR 677C>T基因型和红细胞四氢叶酸水平有关。这些分析结果表明，如果母体CCL-2基因型与脊柱裂的风险相关，这种关系可能比最初假设的更复杂，可能取决于叶酸摄入量、MTHFR 677C>T基因型、叶酸衍生物的分布以及免疫/炎症活性。
Women with the AA genotype at the (−2518) A>G promoter polymorphism of CCL-2, which encodes the potent pro-inflammatory chemokine monocyte chemoattractant protein 1 (MCP-1), may be at increased risk for having offspring affected by spina bifida. As the A allele at this locus has been associated with decreased transcription of MCP-1 mRNA relative to the G allele, the observed genetic association suggests that the risk of spina bifida may be increased in the offspring of women with low MCP-1 levels. The present study was undertaken to identify potential determinants of MCP-1 levels in women of reproductive age. A small cohort of Caucasian and African-American women of reproductive age was recruited to participate in an exploratory investigation of the determinants of several disease-related, biochemical phenotypes, including MCP-1. Subjects completed a brief questionnaire and provided a fasting blood sample for biochemical and genetic studies. Potential biochemical, genetic and lifestyle factors were assessed for their association with MCP-1 levels using linear regression analyses. In this cohort, MCP-1 levels were significantly higher in Caucasians as compared to African-Americans. Further, among women of both races, there was evidence that MCP-1 levels were associated with smoking status, MTHFR 677C>T genotype and red blood cell tetrahydrofolate levels. The results of these analyses indicate that, if maternal CCL-2 genotype is related to the risk of spina bifida, this relationship is likely to be more complex than initially hypothesized, perhaps depending upon folate intake, MTHFR 677C>T genotype, the distribution of folate derivatives, and immune/inflammatory activity.
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影响因子：
158.5
作者：
CZEIZEL, AE;DUDAS, I
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DUDAS, I
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通讯作者：
Whitehead, Alexander S.