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

Abstract

Objectives Examine the relationship between specific polymorphisms in the fibrinogen, homocysteine and intercellular adhesion molecule-1 genes and their respective inflammatory biomarker concentrations at baseline in women from different race/ethnic groups. Background Although inflammation is a core element of atherogenesis and plasma levels of fibrinogen, homocysteine and intercellular adhesion molecule-1 (ICAM-1) differ by race/ethnicity, little is known about the role of genetic polymorphisms in the fibrinogen (FGB), methylenetetrahydrofolate reductase (MTHFR), and intercellular adhesion molecule-1 (ICAM-1) genes in determining plasma levels of these biomarkers. 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 to 21.9%) but significantly lower in black women (6.6%, p< 0.001). The minor allele was associated with elevated fibrinogen 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 fibrinogen 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 <0.001). 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 fibrinogen, homocysteine and intercellular adhesion molecule-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.

Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis

“…The presence of the T allele (MTHFR C677T) renders the enzyme thermolabile reducing its enzymatic activity, which may cause elevated plasma levels of homocysteine. However, the ethnic composition and the location of sampling can influence the frequency of MTHFR genotypes 20 21. One research indicated that the prevalence of the 677 T allele varied from 9.34% to 40.53% in different ethnic groups, the lowest being demonstrated for South Asians and the highest for East Asians 22.…”

The Association Between Variants on Chromosome 9p21 and Inflammatory Biomarkers in Ethnically Diverse Women With Coronary Heart Disease: A Pilot Study

“…The few studies that have examined interethnic differences in inflammation reveal inconsistent findings. Although investigators have reported that apparently healthy White women have higher ICAM-1 levels (Albert et al, 2009) and higher TNF-α levels than Black women (Hyatt et al, 2009), others found that apparently healthy Blacks had higher inflammatory biomarker concentrations than Whites (Albert, 2007; Carroll et al, 2009; Ford, Giles, Mokdad, & Myers, 2004; Walston et al, 2007). Some studies investigating the association between cytokine polymorphisms and race suggest the potential for systemic inflammatory upregulation in Blacks (Ness, Haggerty, Harger, & Ferrell, 2004), while others do not (Van Dyke, Cote, Wenzlaff, Land, & Schwartz, 2009).…”

Most Important Articles on Cardiovascular Disease Among Racial and Ethnic Minorities

“…Of these, 29 986 (81.6%) were in whites, 4745 (12.9%) were in blacks, and 2017 (5.5%) were in Hispanics. The authors compared early (during the first 6 months) and late (after 6 months) posttransplant survival in recipients belonging to these groups in 5 successive eras (1987-1992, 1993-1996, 1997-2000, 2001-2004, 2005-2008 53,54 Studies are required to understand the impact of this greater burden of risk in racial and ethnic minorities and their potential interaction with socioeconomic variables related to minority status such as poverty, unemployment, impaired access to health care, and discrimination.…”

“…[50][51][52] Minority populations may also have a higher prevalence of nontraditional cardiovascular risk markers such as C-reactive protein, lipoprotein(a), fibrinogen, and specific intracellular adhesion molecules. 53,54 Studies are required to understand the impact of this greater burden of risk in racial and ethnic minorities and their potential interaction with socioeconomic variables related to minority status such as poverty, unemployment, impaired access to health care, and discrimination.…”

“…Of these, 29 986 (81.6%) were in whites, 4745 (12.9%) were in blacks, and 2017 (5.5%) were in Hispanics. The authors compared early (during the first 6 months) and late (after 6 months) posttransplant survival in recipients belonging to these groups in 5 successive eras (1987-1992, 1993-1996, 1997-2000, 2001-2004, 2005-2008 53,54 Studies are required to understand the impact of this greater burden of risk in racial and ethnic minorities and their potential interaction with socioeconomic variables related to minority status such as poverty, unemployment, impaired access to health care, and discrimination.The following section contains studies pertinent to cardiovascular risk among minorities such as the predictive accuracy of traditional Framingham risk factors in blacks and Hispanics relative to whites, the utility of lipoprotein(a) as a risk marker in blacks, the presence of racial disparities in control of hypertension, and the impact of socioeconomic variables on cardiovascular outcomes. …”