| Candidate genetic variants in the fibrinogen, methylenetetrahydrofolate reductase, and intercellular adhesion molecule-1 genes and plasma levels of fibrinogen, homocysteine, and intercellular adhesion molecule-1 among various race/ethnic groups: data from the Women's Genome Health Study. | |
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MedLine Citation:
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PMID: 19332210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Although inflammation is a core element of atherogenesis and plasma levels of fibrinogen (FGB), homocysteine, and intercellular adhesion molecule-1 (ICAM-1) differ by race/ethnicity, little is known about the role of genetic polymorphisms in the FGB, methylenetetrahydrofolate reductase (MTHFR), and ICAM-1 genes in determining plasma levels of these biomarkers. We examined the relationship between specific polymorphisms in the FGB, homocysteine, and ICAM-1 genes and their respective inflammatory biomarker concentrations at baseline in women from different race/ethnic groups. METHODS: We genotyped specific polymorphisms in FGB (-455G>A/rs1800790), MTHFR (677C>T/rs1801133), and ICAM-1 (Lys56Met/rs5491 and Gly241Arg/rs1799969) at baseline and evaluated their relationship with respective inflammatory biomarker levels in 25,565 white, 476 African-American (black), 277 Hispanic, and 370 Asian women participating in the Women's Genome Health Study. RESULTS: Overall, the minor allele frequencies for -455G>A were similar among white, Hispanic, and Asian women (17.2%-21.9%) but significantly lower in black women (6.6%, P < .001). The minor allele was associated with elevated FGB levels only in whites and Asians. After adjustment for age, body mass index, smoking, postmenopausal status, diabetes, hormone replacement therapy use, hypertension, and education, black women had the highest FGB levels compared to other race/ethnic groups. The minor allele frequency of the MTHFR 677C>T polymorphism was lowest in blacks (blacks 12.1%, whites 33.1%, Hispanics 39.0%, Asians 24.0%), and the T allele was only significantly associated with homocysteine levels in white women. Among whites, Hispanics, and Asians, the Lys56Met polymorphism was rare compared to the frequency in blacks (P < .001). Neither the Lys56Met nor Gly241Arg polymorphisms were common in Asians. Nonetheless, both polymorphisms were generally associated with lower ICAM-1 levels; the lowest levels were observed in black women. CONCLUSION: We found significant associations between certain candidate genetic polymorphisms and baseline plasma levels of FGB, homocysteine, and ICAM-1 in women from various race/ethnic groups. The present investigation is hypothesis generating and suggests genetic determination of differential concentrations of these atherosclerosis-related inflammatory biomarkers differ among various race/ethnic groups. |
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Authors:
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Michelle A Albert; Guillaume Pare; Alanna Morris; Lynda Rose; Julie Buring; Paul M Ridker; Robert Y L Zee |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American heart journal Volume: 157 ISSN: 1097-6744 ISO Abbreviation: Am. Heart J. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-31 Completed Date: 2009-04-21 Revised Date: 2013-02-28 |
Medline Journal Info:
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Nlm Unique ID: 0370465 Medline TA: Am Heart J Country: United States |
Other Details:
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Languages: eng Pagination: 777-83.e1 Citation Subset: AIM; IM |
Affiliation:
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Center for Cardiovascular Disease Prevention, Donald W. Reynolds Center for Cardiovascular Disease Research, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA. maalbert@partners.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cardiovascular Diseases
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blood,
ethnology,
genetics* Cross-Sectional Studies DNA / genetics* Ethnic Groups* Female Fibrinogen / genetics*, metabolism Gene Frequency Genetic Variation* Humans Intercellular Adhesion Molecule-1 / blood, genetics* Methylenetetrahydrofolate Reductase (NADPH2) / blood, genetics* Middle Aged Morbidity United States / epidemiology Women's Health / ethnology |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA047988/CA/NCI NIH HHS; R01 CA047988-09/CA/NCI NIH HHS; R01 CA047988-10/CA/NCI NIH HHS; R01 CA047988-11/CA/NCI NIH HHS; R01 CA047988-12/CA/NCI NIH HHS; R01 CA047988-13/CA/NCI NIH HHS; R01 CA047988-14/CA/NCI NIH HHS; R01 CA047988-15/CA/NCI NIH HHS; R01 CA047988-16/CA/NCI NIH HHS; R01 CA047988-17/CA/NCI NIH HHS; R01 CA047988-18/CA/NCI NIH HHS; R01 HL043851/HL/NHLBI NIH HHS; R01 HL043851-09/HL/NHLBI NIH HHS; R01 HL043851-10/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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126547-89-5/Intercellular Adhesion Molecule-1; 9001-32-5/Fibrinogen; 9007-49-2/DNA; EC 1.5.1.20/Methylenetetrahydrofolate Reductase (NADPH2) |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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