Genetic and Biochemical Determinants of Serum Concentrations of Monocyte Chemoattractant Protein-1, a Potential Neural Tube Defect Risk Factor

Overview

Journal Birth Defects Res A Clin Mol Teratol

Publisher Wiley

Date 2008 Oct 22

PMID 18937353

Citations 8

Authors

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

Affiliations

Soon will be listed here.

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.

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