Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor
✍ Scribed by Zhi-Yong Lu; Megan Morales; Stephanie Khartulyari; Minghua Mei; Kristen M. Murphy; Anna Stanislawska-Sachadyn; Carolyn M. Summers; Yuehua Huang; Joan M. Von Feldt; Ian A. Blair; Laura E. Mitchell; Alexander S. Whitehead
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 93 KB
- Volume
- 82
- Category
- Article
- ISSN
- 1542-0752
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✦ Synopsis
Abstract
BACKGROUND:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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. Birth Defects Research (Part A) 82:736–741, 2008. © 2008 Wiley‐Liss, Inc.